Transcriptional profiling defines dynamics of parasite tissue sequestration during malaria infection

Background During intra-erythrocytic development, late asexually replicating Plasmodium falciparum parasites sequester from peripheral circulation. This facilitates chronic infection and is linked to severe disease and organ-specific pathology including cerebral and placental malaria. Immature gametocytes - sexual stage precursor cells - likewise disappear from circulation. Recent work has demonstrated that these sexual stage parasites are located in the hematopoietic system of the bone marrow before mature gametocytes are released into the bloodstream to facilitate mosquito transmission. However, as sequestration occurs only in vivo and not during in vitro culture, the mechanisms by which it is regulated and enacted (particularly by the gametocyte stage) remain poorly understood. Results We generated the most comprehensive P. falciparum functional gene network to date by integrating global transcriptional data from a large set of asexual and sexual in vitro samples, patient-derived in vivo samples, and a new set of in vitro samples profiling sexual commitment. We defined more than 250 functional modules (clusters) of genes that are co-expressed primarily during the intra-erythrocytic parasite cycle, including 35 during sexual commitment and gametocyte development. Comparing the in vivo and in vitro datasets allowed us, for the first time, to map the time point of asexual parasite sequestration in patients to 22 hours post-invasion, confirming previous in vitro observations on the dynamics of host cell modification and cytoadherence. Moreover, we were able to define the properties of gametocyte sequestration, demonstrating the presence of two circulating gametocyte populations: gametocyte rings between 0 and approximately 30 hours post-invasion and mature gametocytes after around 7 days post-invasion. Conclusions This study provides a bioinformatics resource for the functional elucidation of parasite life cycle dynamics and specifically demonstrates the presence of the gametocyte ring stages in circulation, adding significantly to our understanding of the dynamics of gametocyte sequestration in vivo. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Pelle, Karell G [verfasserIn] Oh, Keunyoung Buchholz, Kathrin Narasimhan, Vagheesh Joice, Regina Milner, Danny A Brancucci, Nicolas MB Ma, Siyuan Voss, Till S Ketman, Ken Seydel, Karl B Taylor, Terrie E Barteneva, Natasha S Huttenhower, Curtis Marti, Matthias

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2015

Schlagwörter:	Malaria Cerebral Malaria Asexual Parasite Flow Sorting Host Cell Invasion

Anmerkung:	© Pelle et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (

Übergeordnetes Werk:	Enthalten in: Genome medicine - London : BioMed Central, 2009, 7(2015), 1 vom: 27. Feb.
Übergeordnetes Werk:	volume:7 ; year:2015 ; number:1 ; day:27 ; month:02

Links:	Volltext

DOI / URN:	10.1186/s13073-015-0133-7

Katalog-ID:	SPR030621712

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520			\|a Background During intra-erythrocytic development, late asexually replicating Plasmodium falciparum parasites sequester from peripheral circulation. This facilitates chronic infection and is linked to severe disease and organ-specific pathology including cerebral and placental malaria. Immature gametocytes - sexual stage precursor cells - likewise disappear from circulation. Recent work has demonstrated that these sexual stage parasites are located in the hematopoietic system of the bone marrow before mature gametocytes are released into the bloodstream to facilitate mosquito transmission. However, as sequestration occurs only in vivo and not during in vitro culture, the mechanisms by which it is regulated and enacted (particularly by the gametocyte stage) remain poorly understood. Results We generated the most comprehensive P. falciparum functional gene network to date by integrating global transcriptional data from a large set of asexual and sexual in vitro samples, patient-derived in vivo samples, and a new set of in vitro samples profiling sexual commitment. We defined more than 250 functional modules (clusters) of genes that are co-expressed primarily during the intra-erythrocytic parasite cycle, including 35 during sexual commitment and gametocyte development. Comparing the in vivo and in vitro datasets allowed us, for the first time, to map the time point of asexual parasite sequestration in patients to 22 hours post-invasion, confirming previous in vitro observations on the dynamics of host cell modification and cytoadherence. Moreover, we were able to define the properties of gametocyte sequestration, demonstrating the presence of two circulating gametocyte populations: gametocyte rings between 0 and approximately 30 hours post-invasion and mature gametocytes after around 7 days post-invasion. Conclusions This study provides a bioinformatics resource for the functional elucidation of parasite life cycle dynamics and specifically demonstrates the presence of the gametocyte ring stages in circulation, adding significantly to our understanding of the dynamics of gametocyte sequestration in vivo.
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allfields	10.1186/s13073-015-0133-7 doi (DE-627)SPR030621712 (SPR)s13073-015-0133-7-e DE-627 ger DE-627 rakwb eng Pelle, Karell G verfasserin aut Transcriptional profiling defines dynamics of parasite tissue sequestration during malaria infection 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Pelle et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background During intra-erythrocytic development, late asexually replicating Plasmodium falciparum parasites sequester from peripheral circulation. This facilitates chronic infection and is linked to severe disease and organ-specific pathology including cerebral and placental malaria. Immature gametocytes - sexual stage precursor cells - likewise disappear from circulation. Recent work has demonstrated that these sexual stage parasites are located in the hematopoietic system of the bone marrow before mature gametocytes are released into the bloodstream to facilitate mosquito transmission. However, as sequestration occurs only in vivo and not during in vitro culture, the mechanisms by which it is regulated and enacted (particularly by the gametocyte stage) remain poorly understood. Results We generated the most comprehensive P. falciparum functional gene network to date by integrating global transcriptional data from a large set of asexual and sexual in vitro samples, patient-derived in vivo samples, and a new set of in vitro samples profiling sexual commitment. We defined more than 250 functional modules (clusters) of genes that are co-expressed primarily during the intra-erythrocytic parasite cycle, including 35 during sexual commitment and gametocyte development. Comparing the in vivo and in vitro datasets allowed us, for the first time, to map the time point of asexual parasite sequestration in patients to 22 hours post-invasion, confirming previous in vitro observations on the dynamics of host cell modification and cytoadherence. Moreover, we were able to define the properties of gametocyte sequestration, demonstrating the presence of two circulating gametocyte populations: gametocyte rings between 0 and approximately 30 hours post-invasion and mature gametocytes after around 7 days post-invasion. Conclusions This study provides a bioinformatics resource for the functional elucidation of parasite life cycle dynamics and specifically demonstrates the presence of the gametocyte ring stages in circulation, adding significantly to our understanding of the dynamics of gametocyte sequestration in vivo. Malaria (dpeaa)DE-He213 Cerebral Malaria (dpeaa)DE-He213 Asexual Parasite (dpeaa)DE-He213 Flow Sorting (dpeaa)DE-He213 Host Cell Invasion (dpeaa)DE-He213 Oh, Keunyoung aut Buchholz, Kathrin aut Narasimhan, Vagheesh aut Joice, Regina aut Milner, Danny A aut Brancucci, Nicolas MB aut Ma, Siyuan aut Voss, Till S aut Ketman, Ken aut Seydel, Karl B aut Taylor, Terrie E aut Barteneva, Natasha S aut Huttenhower, Curtis aut Marti, Matthias aut Enthalten in Genome medicine London : BioMed Central, 2009 7(2015), 1 vom: 27. Feb. (DE-627)594424275 (DE-600)2484394-5 1756-994X nnns volume:7 year:2015 number:1 day:27 month:02 https://dx.doi.org/10.1186/s13073-015-0133-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2015 1 27 02
spelling	10.1186/s13073-015-0133-7 doi (DE-627)SPR030621712 (SPR)s13073-015-0133-7-e DE-627 ger DE-627 rakwb eng Pelle, Karell G verfasserin aut Transcriptional profiling defines dynamics of parasite tissue sequestration during malaria infection 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Pelle et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background During intra-erythrocytic development, late asexually replicating Plasmodium falciparum parasites sequester from peripheral circulation. This facilitates chronic infection and is linked to severe disease and organ-specific pathology including cerebral and placental malaria. Immature gametocytes - sexual stage precursor cells - likewise disappear from circulation. Recent work has demonstrated that these sexual stage parasites are located in the hematopoietic system of the bone marrow before mature gametocytes are released into the bloodstream to facilitate mosquito transmission. However, as sequestration occurs only in vivo and not during in vitro culture, the mechanisms by which it is regulated and enacted (particularly by the gametocyte stage) remain poorly understood. Results We generated the most comprehensive P. falciparum functional gene network to date by integrating global transcriptional data from a large set of asexual and sexual in vitro samples, patient-derived in vivo samples, and a new set of in vitro samples profiling sexual commitment. We defined more than 250 functional modules (clusters) of genes that are co-expressed primarily during the intra-erythrocytic parasite cycle, including 35 during sexual commitment and gametocyte development. Comparing the in vivo and in vitro datasets allowed us, for the first time, to map the time point of asexual parasite sequestration in patients to 22 hours post-invasion, confirming previous in vitro observations on the dynamics of host cell modification and cytoadherence. Moreover, we were able to define the properties of gametocyte sequestration, demonstrating the presence of two circulating gametocyte populations: gametocyte rings between 0 and approximately 30 hours post-invasion and mature gametocytes after around 7 days post-invasion. Conclusions This study provides a bioinformatics resource for the functional elucidation of parasite life cycle dynamics and specifically demonstrates the presence of the gametocyte ring stages in circulation, adding significantly to our understanding of the dynamics of gametocyte sequestration in vivo. Malaria (dpeaa)DE-He213 Cerebral Malaria (dpeaa)DE-He213 Asexual Parasite (dpeaa)DE-He213 Flow Sorting (dpeaa)DE-He213 Host Cell Invasion (dpeaa)DE-He213 Oh, Keunyoung aut Buchholz, Kathrin aut Narasimhan, Vagheesh aut Joice, Regina aut Milner, Danny A aut Brancucci, Nicolas MB aut Ma, Siyuan aut Voss, Till S aut Ketman, Ken aut Seydel, Karl B aut Taylor, Terrie E aut Barteneva, Natasha S aut Huttenhower, Curtis aut Marti, Matthias aut Enthalten in Genome medicine London : BioMed Central, 2009 7(2015), 1 vom: 27. Feb. (DE-627)594424275 (DE-600)2484394-5 1756-994X nnns volume:7 year:2015 number:1 day:27 month:02 https://dx.doi.org/10.1186/s13073-015-0133-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2015 1 27 02
allfields_unstemmed	10.1186/s13073-015-0133-7 doi (DE-627)SPR030621712 (SPR)s13073-015-0133-7-e DE-627 ger DE-627 rakwb eng Pelle, Karell G verfasserin aut Transcriptional profiling defines dynamics of parasite tissue sequestration during malaria infection 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Pelle et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background During intra-erythrocytic development, late asexually replicating Plasmodium falciparum parasites sequester from peripheral circulation. This facilitates chronic infection and is linked to severe disease and organ-specific pathology including cerebral and placental malaria. Immature gametocytes - sexual stage precursor cells - likewise disappear from circulation. Recent work has demonstrated that these sexual stage parasites are located in the hematopoietic system of the bone marrow before mature gametocytes are released into the bloodstream to facilitate mosquito transmission. However, as sequestration occurs only in vivo and not during in vitro culture, the mechanisms by which it is regulated and enacted (particularly by the gametocyte stage) remain poorly understood. Results We generated the most comprehensive P. falciparum functional gene network to date by integrating global transcriptional data from a large set of asexual and sexual in vitro samples, patient-derived in vivo samples, and a new set of in vitro samples profiling sexual commitment. We defined more than 250 functional modules (clusters) of genes that are co-expressed primarily during the intra-erythrocytic parasite cycle, including 35 during sexual commitment and gametocyte development. Comparing the in vivo and in vitro datasets allowed us, for the first time, to map the time point of asexual parasite sequestration in patients to 22 hours post-invasion, confirming previous in vitro observations on the dynamics of host cell modification and cytoadherence. Moreover, we were able to define the properties of gametocyte sequestration, demonstrating the presence of two circulating gametocyte populations: gametocyte rings between 0 and approximately 30 hours post-invasion and mature gametocytes after around 7 days post-invasion. Conclusions This study provides a bioinformatics resource for the functional elucidation of parasite life cycle dynamics and specifically demonstrates the presence of the gametocyte ring stages in circulation, adding significantly to our understanding of the dynamics of gametocyte sequestration in vivo. Malaria (dpeaa)DE-He213 Cerebral Malaria (dpeaa)DE-He213 Asexual Parasite (dpeaa)DE-He213 Flow Sorting (dpeaa)DE-He213 Host Cell Invasion (dpeaa)DE-He213 Oh, Keunyoung aut Buchholz, Kathrin aut Narasimhan, Vagheesh aut Joice, Regina aut Milner, Danny A aut Brancucci, Nicolas MB aut Ma, Siyuan aut Voss, Till S aut Ketman, Ken aut Seydel, Karl B aut Taylor, Terrie E aut Barteneva, Natasha S aut Huttenhower, Curtis aut Marti, Matthias aut Enthalten in Genome medicine London : BioMed Central, 2009 7(2015), 1 vom: 27. Feb. (DE-627)594424275 (DE-600)2484394-5 1756-994X nnns volume:7 year:2015 number:1 day:27 month:02 https://dx.doi.org/10.1186/s13073-015-0133-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2015 1 27 02
allfieldsGer	10.1186/s13073-015-0133-7 doi (DE-627)SPR030621712 (SPR)s13073-015-0133-7-e DE-627 ger DE-627 rakwb eng Pelle, Karell G verfasserin aut Transcriptional profiling defines dynamics of parasite tissue sequestration during malaria infection 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Pelle et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background During intra-erythrocytic development, late asexually replicating Plasmodium falciparum parasites sequester from peripheral circulation. This facilitates chronic infection and is linked to severe disease and organ-specific pathology including cerebral and placental malaria. Immature gametocytes - sexual stage precursor cells - likewise disappear from circulation. Recent work has demonstrated that these sexual stage parasites are located in the hematopoietic system of the bone marrow before mature gametocytes are released into the bloodstream to facilitate mosquito transmission. However, as sequestration occurs only in vivo and not during in vitro culture, the mechanisms by which it is regulated and enacted (particularly by the gametocyte stage) remain poorly understood. Results We generated the most comprehensive P. falciparum functional gene network to date by integrating global transcriptional data from a large set of asexual and sexual in vitro samples, patient-derived in vivo samples, and a new set of in vitro samples profiling sexual commitment. We defined more than 250 functional modules (clusters) of genes that are co-expressed primarily during the intra-erythrocytic parasite cycle, including 35 during sexual commitment and gametocyte development. Comparing the in vivo and in vitro datasets allowed us, for the first time, to map the time point of asexual parasite sequestration in patients to 22 hours post-invasion, confirming previous in vitro observations on the dynamics of host cell modification and cytoadherence. Moreover, we were able to define the properties of gametocyte sequestration, demonstrating the presence of two circulating gametocyte populations: gametocyte rings between 0 and approximately 30 hours post-invasion and mature gametocytes after around 7 days post-invasion. Conclusions This study provides a bioinformatics resource for the functional elucidation of parasite life cycle dynamics and specifically demonstrates the presence of the gametocyte ring stages in circulation, adding significantly to our understanding of the dynamics of gametocyte sequestration in vivo. Malaria (dpeaa)DE-He213 Cerebral Malaria (dpeaa)DE-He213 Asexual Parasite (dpeaa)DE-He213 Flow Sorting (dpeaa)DE-He213 Host Cell Invasion (dpeaa)DE-He213 Oh, Keunyoung aut Buchholz, Kathrin aut Narasimhan, Vagheesh aut Joice, Regina aut Milner, Danny A aut Brancucci, Nicolas MB aut Ma, Siyuan aut Voss, Till S aut Ketman, Ken aut Seydel, Karl B aut Taylor, Terrie E aut Barteneva, Natasha S aut Huttenhower, Curtis aut Marti, Matthias aut Enthalten in Genome medicine London : BioMed Central, 2009 7(2015), 1 vom: 27. Feb. (DE-627)594424275 (DE-600)2484394-5 1756-994X nnns volume:7 year:2015 number:1 day:27 month:02 https://dx.doi.org/10.1186/s13073-015-0133-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2015 1 27 02
allfieldsSound	10.1186/s13073-015-0133-7 doi (DE-627)SPR030621712 (SPR)s13073-015-0133-7-e DE-627 ger DE-627 rakwb eng Pelle, Karell G verfasserin aut Transcriptional profiling defines dynamics of parasite tissue sequestration during malaria infection 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Pelle et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background During intra-erythrocytic development, late asexually replicating Plasmodium falciparum parasites sequester from peripheral circulation. This facilitates chronic infection and is linked to severe disease and organ-specific pathology including cerebral and placental malaria. Immature gametocytes - sexual stage precursor cells - likewise disappear from circulation. Recent work has demonstrated that these sexual stage parasites are located in the hematopoietic system of the bone marrow before mature gametocytes are released into the bloodstream to facilitate mosquito transmission. However, as sequestration occurs only in vivo and not during in vitro culture, the mechanisms by which it is regulated and enacted (particularly by the gametocyte stage) remain poorly understood. Results We generated the most comprehensive P. falciparum functional gene network to date by integrating global transcriptional data from a large set of asexual and sexual in vitro samples, patient-derived in vivo samples, and a new set of in vitro samples profiling sexual commitment. We defined more than 250 functional modules (clusters) of genes that are co-expressed primarily during the intra-erythrocytic parasite cycle, including 35 during sexual commitment and gametocyte development. Comparing the in vivo and in vitro datasets allowed us, for the first time, to map the time point of asexual parasite sequestration in patients to 22 hours post-invasion, confirming previous in vitro observations on the dynamics of host cell modification and cytoadherence. Moreover, we were able to define the properties of gametocyte sequestration, demonstrating the presence of two circulating gametocyte populations: gametocyte rings between 0 and approximately 30 hours post-invasion and mature gametocytes after around 7 days post-invasion. Conclusions This study provides a bioinformatics resource for the functional elucidation of parasite life cycle dynamics and specifically demonstrates the presence of the gametocyte ring stages in circulation, adding significantly to our understanding of the dynamics of gametocyte sequestration in vivo. Malaria (dpeaa)DE-He213 Cerebral Malaria (dpeaa)DE-He213 Asexual Parasite (dpeaa)DE-He213 Flow Sorting (dpeaa)DE-He213 Host Cell Invasion (dpeaa)DE-He213 Oh, Keunyoung aut Buchholz, Kathrin aut Narasimhan, Vagheesh aut Joice, Regina aut Milner, Danny A aut Brancucci, Nicolas MB aut Ma, Siyuan aut Voss, Till S aut Ketman, Ken aut Seydel, Karl B aut Taylor, Terrie E aut Barteneva, Natasha S aut Huttenhower, Curtis aut Marti, Matthias aut Enthalten in Genome medicine London : BioMed Central, 2009 7(2015), 1 vom: 27. Feb. (DE-627)594424275 (DE-600)2484394-5 1756-994X nnns volume:7 year:2015 number:1 day:27 month:02 https://dx.doi.org/10.1186/s13073-015-0133-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2015 1 27 02
language	English
source	Enthalten in Genome medicine 7(2015), 1 vom: 27. Feb. volume:7 year:2015 number:1 day:27 month:02
sourceStr	Enthalten in Genome medicine 7(2015), 1 vom: 27. Feb. volume:7 year:2015 number:1 day:27 month:02
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Malaria Cerebral Malaria Asexual Parasite Flow Sorting Host Cell Invasion
isfreeaccess_bool	true
container_title	Genome medicine
authorswithroles_txt_mv	Pelle, Karell G @@aut@@ Oh, Keunyoung @@aut@@ Buchholz, Kathrin @@aut@@ Narasimhan, Vagheesh @@aut@@ Joice, Regina @@aut@@ Milner, Danny A @@aut@@ Brancucci, Nicolas MB @@aut@@ Ma, Siyuan @@aut@@ Voss, Till S @@aut@@ Ketman, Ken @@aut@@ Seydel, Karl B @@aut@@ Taylor, Terrie E @@aut@@ Barteneva, Natasha S @@aut@@ Huttenhower, Curtis @@aut@@ Marti, Matthias @@aut@@
publishDateDaySort_date	2015-02-27T00:00:00Z
hierarchy_top_id	594424275
id	SPR030621712
language_de	englisch
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Results We generated the most comprehensive P. falciparum functional gene network to date by integrating global transcriptional data from a large set of asexual and sexual in vitro samples, patient-derived in vivo samples, and a new set of in vitro samples profiling sexual commitment. We defined more than 250 functional modules (clusters) of genes that are co-expressed primarily during the intra-erythrocytic parasite cycle, including 35 during sexual commitment and gametocyte development. Comparing the in vivo and in vitro datasets allowed us, for the first time, to map the time point of asexual parasite sequestration in patients to 22 hours post-invasion, confirming previous in vitro observations on the dynamics of host cell modification and cytoadherence. Moreover, we were able to define the properties of gametocyte sequestration, demonstrating the presence of two circulating gametocyte populations: gametocyte rings between 0 and approximately 30 hours post-invasion and mature gametocytes after around 7 days post-invasion. 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author	Pelle, Karell G
spellingShingle	Pelle, Karell G misc Malaria misc Cerebral Malaria misc Asexual Parasite misc Flow Sorting misc Host Cell Invasion Transcriptional profiling defines dynamics of parasite tissue sequestration during malaria infection
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topic_title	Transcriptional profiling defines dynamics of parasite tissue sequestration during malaria infection Malaria (dpeaa)DE-He213 Cerebral Malaria (dpeaa)DE-He213 Asexual Parasite (dpeaa)DE-He213 Flow Sorting (dpeaa)DE-He213 Host Cell Invasion (dpeaa)DE-He213
topic	misc Malaria misc Cerebral Malaria misc Asexual Parasite misc Flow Sorting misc Host Cell Invasion
topic_unstemmed	misc Malaria misc Cerebral Malaria misc Asexual Parasite misc Flow Sorting misc Host Cell Invasion
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title	Transcriptional profiling defines dynamics of parasite tissue sequestration during malaria infection
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title_full	Transcriptional profiling defines dynamics of parasite tissue sequestration during malaria infection
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author_browse	Pelle, Karell G Oh, Keunyoung Buchholz, Kathrin Narasimhan, Vagheesh Joice, Regina Milner, Danny A Brancucci, Nicolas MB Ma, Siyuan Voss, Till S Ketman, Ken Seydel, Karl B Taylor, Terrie E Barteneva, Natasha S Huttenhower, Curtis Marti, Matthias
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doi_str_mv	10.1186/s13073-015-0133-7
title_sort	transcriptional profiling defines dynamics of parasite tissue sequestration during malaria infection
title_auth	Transcriptional profiling defines dynamics of parasite tissue sequestration during malaria infection
abstract	Background During intra-erythrocytic development, late asexually replicating Plasmodium falciparum parasites sequester from peripheral circulation. This facilitates chronic infection and is linked to severe disease and organ-specific pathology including cerebral and placental malaria. Immature gametocytes - sexual stage precursor cells - likewise disappear from circulation. Recent work has demonstrated that these sexual stage parasites are located in the hematopoietic system of the bone marrow before mature gametocytes are released into the bloodstream to facilitate mosquito transmission. However, as sequestration occurs only in vivo and not during in vitro culture, the mechanisms by which it is regulated and enacted (particularly by the gametocyte stage) remain poorly understood. Results We generated the most comprehensive P. falciparum functional gene network to date by integrating global transcriptional data from a large set of asexual and sexual in vitro samples, patient-derived in vivo samples, and a new set of in vitro samples profiling sexual commitment. We defined more than 250 functional modules (clusters) of genes that are co-expressed primarily during the intra-erythrocytic parasite cycle, including 35 during sexual commitment and gametocyte development. Comparing the in vivo and in vitro datasets allowed us, for the first time, to map the time point of asexual parasite sequestration in patients to 22 hours post-invasion, confirming previous in vitro observations on the dynamics of host cell modification and cytoadherence. Moreover, we were able to define the properties of gametocyte sequestration, demonstrating the presence of two circulating gametocyte populations: gametocyte rings between 0 and approximately 30 hours post-invasion and mature gametocytes after around 7 days post-invasion. Conclusions This study provides a bioinformatics resource for the functional elucidation of parasite life cycle dynamics and specifically demonstrates the presence of the gametocyte ring stages in circulation, adding significantly to our understanding of the dynamics of gametocyte sequestration in vivo. © Pelle et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
abstractGer	Background During intra-erythrocytic development, late asexually replicating Plasmodium falciparum parasites sequester from peripheral circulation. This facilitates chronic infection and is linked to severe disease and organ-specific pathology including cerebral and placental malaria. Immature gametocytes - sexual stage precursor cells - likewise disappear from circulation. Recent work has demonstrated that these sexual stage parasites are located in the hematopoietic system of the bone marrow before mature gametocytes are released into the bloodstream to facilitate mosquito transmission. However, as sequestration occurs only in vivo and not during in vitro culture, the mechanisms by which it is regulated and enacted (particularly by the gametocyte stage) remain poorly understood. Results We generated the most comprehensive P. falciparum functional gene network to date by integrating global transcriptional data from a large set of asexual and sexual in vitro samples, patient-derived in vivo samples, and a new set of in vitro samples profiling sexual commitment. We defined more than 250 functional modules (clusters) of genes that are co-expressed primarily during the intra-erythrocytic parasite cycle, including 35 during sexual commitment and gametocyte development. Comparing the in vivo and in vitro datasets allowed us, for the first time, to map the time point of asexual parasite sequestration in patients to 22 hours post-invasion, confirming previous in vitro observations on the dynamics of host cell modification and cytoadherence. Moreover, we were able to define the properties of gametocyte sequestration, demonstrating the presence of two circulating gametocyte populations: gametocyte rings between 0 and approximately 30 hours post-invasion and mature gametocytes after around 7 days post-invasion. Conclusions This study provides a bioinformatics resource for the functional elucidation of parasite life cycle dynamics and specifically demonstrates the presence of the gametocyte ring stages in circulation, adding significantly to our understanding of the dynamics of gametocyte sequestration in vivo. © Pelle et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
abstract_unstemmed	Background During intra-erythrocytic development, late asexually replicating Plasmodium falciparum parasites sequester from peripheral circulation. This facilitates chronic infection and is linked to severe disease and organ-specific pathology including cerebral and placental malaria. Immature gametocytes - sexual stage precursor cells - likewise disappear from circulation. Recent work has demonstrated that these sexual stage parasites are located in the hematopoietic system of the bone marrow before mature gametocytes are released into the bloodstream to facilitate mosquito transmission. However, as sequestration occurs only in vivo and not during in vitro culture, the mechanisms by which it is regulated and enacted (particularly by the gametocyte stage) remain poorly understood. Results We generated the most comprehensive P. falciparum functional gene network to date by integrating global transcriptional data from a large set of asexual and sexual in vitro samples, patient-derived in vivo samples, and a new set of in vitro samples profiling sexual commitment. We defined more than 250 functional modules (clusters) of genes that are co-expressed primarily during the intra-erythrocytic parasite cycle, including 35 during sexual commitment and gametocyte development. Comparing the in vivo and in vitro datasets allowed us, for the first time, to map the time point of asexual parasite sequestration in patients to 22 hours post-invasion, confirming previous in vitro observations on the dynamics of host cell modification and cytoadherence. Moreover, we were able to define the properties of gametocyte sequestration, demonstrating the presence of two circulating gametocyte populations: gametocyte rings between 0 and approximately 30 hours post-invasion and mature gametocytes after around 7 days post-invasion. Conclusions This study provides a bioinformatics resource for the functional elucidation of parasite life cycle dynamics and specifically demonstrates the presence of the gametocyte ring stages in circulation, adding significantly to our understanding of the dynamics of gametocyte sequestration in vivo. © Pelle et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
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container_issue	1
title_short	Transcriptional profiling defines dynamics of parasite tissue sequestration during malaria infection
url	https://dx.doi.org/10.1186/s13073-015-0133-7
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author2	Oh, Keunyoung Buchholz, Kathrin Narasimhan, Vagheesh Joice, Regina Milner, Danny A Brancucci, Nicolas MB Ma, Siyuan Voss, Till S Ketman, Ken Seydel, Karl B Taylor, Terrie E Barteneva, Natasha S Huttenhower, Curtis Marti, Matthias
author2Str	Oh, Keunyoung Buchholz, Kathrin Narasimhan, Vagheesh Joice, Regina Milner, Danny A Brancucci, Nicolas MB Ma, Siyuan Voss, Till S Ketman, Ken Seydel, Karl B Taylor, Terrie E Barteneva, Natasha S Huttenhower, Curtis Marti, Matthias
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up_date	2024-07-03T19:11:03.916Z
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