Spliceosome inhibitor induces human hematopoietic progenitor cell reprogramming toward stemness

Abstract The application of hematopoietic stem cells (HSCs) has been restricted due to limited cell sources and conventional methods for generating these cells by cell expansion and pluripotent stem cell differentiation have not been clinically achieved. Cell reprogramming technique provides a new h...
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Autor*in:	Dong, Liaoliao [verfasserIn] Wei, Chuijin Xiong, Shumin Yu, Ping Zhou, Ren Cheng, Lin

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	Cell reprogramming Human hematopoietic stem/progenitor cells Spliceosome Small molecule compound Lineage tracing

Anmerkung:	© The Author(s) 2022

Übergeordnetes Werk:	Enthalten in: Experimental hematology & oncology - London : Biomed Central, 2012, 11(2022), 1 vom: 10. Juni
Übergeordnetes Werk:	volume:11 ; year:2022 ; number:1 ; day:10 ; month:06

Links:	Volltext

DOI / URN:	10.1186/s40164-022-00288-9

Katalog-ID:	SPR050776371

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allfields	10.1186/s40164-022-00288-9 doi (DE-627)SPR050776371 (SPR)s40164-022-00288-9-e DE-627 ger DE-627 rakwb eng Dong, Liaoliao verfasserin aut Spliceosome inhibitor induces human hematopoietic progenitor cell reprogramming toward stemness 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Abstract The application of hematopoietic stem cells (HSCs) has been restricted due to limited cell sources and conventional methods for generating these cells by cell expansion and pluripotent stem cell differentiation have not been clinically achieved. Cell reprogramming technique provides a new hope for generating desirable cells. We previously reported that mouse differentiated hematopoietic cell reprogramming could be induced by small molecule compounds to generate hematopoietic stem/progenitor-like cells, whether the human hematopoietic cells could also be reprogrammed into HSCs by chemical compounds remains elusive. Here, we demonstrated for the first time that human committed hematopoietic progenitors could be reprogrammed into multipotent progenitors by spliceosome inhibitor. Combination of single cell RNA-sequencing and genetic lineage tracing including exogenous barcodes and endogenous mitochondrial DNA mutations confirmed the reprogramming procession. Although the small chemical compound inhibiting spliceosome function only induces the differentiated hematopoietic progenitors to acquire plasticity and reprograms them into multipotent progenitors but not stem cells so far, this study still provides a proof-of-concept strategy for generating HSCs based on combining two independent steps together in future, first differentiating rare HSCs into large number of progenitors then reprogramming these progenitors into huge number of HSCs. Further dissecting the mechanism underlying spliceosome inhibitor-induced human hematopoietic cell reprogramming in future will help us comprehensively understanding not only the chemical reprogramming to generate desirable human cells for clinical translation but also hematopoiesis under physiological and pathological conditions. Cell reprogramming (dpeaa)DE-He213 Human hematopoietic stem/progenitor cells (dpeaa)DE-He213 Spliceosome (dpeaa)DE-He213 Small molecule compound (dpeaa)DE-He213 Lineage tracing (dpeaa)DE-He213 Wei, Chuijin aut Xiong, Shumin aut Yu, Ping aut Zhou, Ren aut Cheng, Lin aut Enthalten in Experimental hematology & oncology London : Biomed Central, 2012 11(2022), 1 vom: 10. Juni (DE-627)718833341 (DE-600)2669066-4 2162-3619 nnns volume:11 year:2022 number:1 day:10 month:06 https://dx.doi.org/10.1186/s40164-022-00288-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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_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 11 2022 1 10 06
spelling	10.1186/s40164-022-00288-9 doi (DE-627)SPR050776371 (SPR)s40164-022-00288-9-e DE-627 ger DE-627 rakwb eng Dong, Liaoliao verfasserin aut Spliceosome inhibitor induces human hematopoietic progenitor cell reprogramming toward stemness 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Abstract The application of hematopoietic stem cells (HSCs) has been restricted due to limited cell sources and conventional methods for generating these cells by cell expansion and pluripotent stem cell differentiation have not been clinically achieved. Cell reprogramming technique provides a new hope for generating desirable cells. We previously reported that mouse differentiated hematopoietic cell reprogramming could be induced by small molecule compounds to generate hematopoietic stem/progenitor-like cells, whether the human hematopoietic cells could also be reprogrammed into HSCs by chemical compounds remains elusive. Here, we demonstrated for the first time that human committed hematopoietic progenitors could be reprogrammed into multipotent progenitors by spliceosome inhibitor. Combination of single cell RNA-sequencing and genetic lineage tracing including exogenous barcodes and endogenous mitochondrial DNA mutations confirmed the reprogramming procession. Although the small chemical compound inhibiting spliceosome function only induces the differentiated hematopoietic progenitors to acquire plasticity and reprograms them into multipotent progenitors but not stem cells so far, this study still provides a proof-of-concept strategy for generating HSCs based on combining two independent steps together in future, first differentiating rare HSCs into large number of progenitors then reprogramming these progenitors into huge number of HSCs. Further dissecting the mechanism underlying spliceosome inhibitor-induced human hematopoietic cell reprogramming in future will help us comprehensively understanding not only the chemical reprogramming to generate desirable human cells for clinical translation but also hematopoiesis under physiological and pathological conditions. Cell reprogramming (dpeaa)DE-He213 Human hematopoietic stem/progenitor cells (dpeaa)DE-He213 Spliceosome (dpeaa)DE-He213 Small molecule compound (dpeaa)DE-He213 Lineage tracing (dpeaa)DE-He213 Wei, Chuijin aut Xiong, Shumin aut Yu, Ping aut Zhou, Ren aut Cheng, Lin aut Enthalten in Experimental hematology & oncology London : Biomed Central, 2012 11(2022), 1 vom: 10. Juni (DE-627)718833341 (DE-600)2669066-4 2162-3619 nnns volume:11 year:2022 number:1 day:10 month:06 https://dx.doi.org/10.1186/s40164-022-00288-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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_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 11 2022 1 10 06
allfields_unstemmed	10.1186/s40164-022-00288-9 doi (DE-627)SPR050776371 (SPR)s40164-022-00288-9-e DE-627 ger DE-627 rakwb eng Dong, Liaoliao verfasserin aut Spliceosome inhibitor induces human hematopoietic progenitor cell reprogramming toward stemness 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Abstract The application of hematopoietic stem cells (HSCs) has been restricted due to limited cell sources and conventional methods for generating these cells by cell expansion and pluripotent stem cell differentiation have not been clinically achieved. Cell reprogramming technique provides a new hope for generating desirable cells. We previously reported that mouse differentiated hematopoietic cell reprogramming could be induced by small molecule compounds to generate hematopoietic stem/progenitor-like cells, whether the human hematopoietic cells could also be reprogrammed into HSCs by chemical compounds remains elusive. Here, we demonstrated for the first time that human committed hematopoietic progenitors could be reprogrammed into multipotent progenitors by spliceosome inhibitor. Combination of single cell RNA-sequencing and genetic lineage tracing including exogenous barcodes and endogenous mitochondrial DNA mutations confirmed the reprogramming procession. Although the small chemical compound inhibiting spliceosome function only induces the differentiated hematopoietic progenitors to acquire plasticity and reprograms them into multipotent progenitors but not stem cells so far, this study still provides a proof-of-concept strategy for generating HSCs based on combining two independent steps together in future, first differentiating rare HSCs into large number of progenitors then reprogramming these progenitors into huge number of HSCs. Further dissecting the mechanism underlying spliceosome inhibitor-induced human hematopoietic cell reprogramming in future will help us comprehensively understanding not only the chemical reprogramming to generate desirable human cells for clinical translation but also hematopoiesis under physiological and pathological conditions. Cell reprogramming (dpeaa)DE-He213 Human hematopoietic stem/progenitor cells (dpeaa)DE-He213 Spliceosome (dpeaa)DE-He213 Small molecule compound (dpeaa)DE-He213 Lineage tracing (dpeaa)DE-He213 Wei, Chuijin aut Xiong, Shumin aut Yu, Ping aut Zhou, Ren aut Cheng, Lin aut Enthalten in Experimental hematology & oncology London : Biomed Central, 2012 11(2022), 1 vom: 10. Juni (DE-627)718833341 (DE-600)2669066-4 2162-3619 nnns volume:11 year:2022 number:1 day:10 month:06 https://dx.doi.org/10.1186/s40164-022-00288-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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_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 11 2022 1 10 06
allfieldsGer	10.1186/s40164-022-00288-9 doi (DE-627)SPR050776371 (SPR)s40164-022-00288-9-e DE-627 ger DE-627 rakwb eng Dong, Liaoliao verfasserin aut Spliceosome inhibitor induces human hematopoietic progenitor cell reprogramming toward stemness 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Abstract The application of hematopoietic stem cells (HSCs) has been restricted due to limited cell sources and conventional methods for generating these cells by cell expansion and pluripotent stem cell differentiation have not been clinically achieved. Cell reprogramming technique provides a new hope for generating desirable cells. We previously reported that mouse differentiated hematopoietic cell reprogramming could be induced by small molecule compounds to generate hematopoietic stem/progenitor-like cells, whether the human hematopoietic cells could also be reprogrammed into HSCs by chemical compounds remains elusive. Here, we demonstrated for the first time that human committed hematopoietic progenitors could be reprogrammed into multipotent progenitors by spliceosome inhibitor. Combination of single cell RNA-sequencing and genetic lineage tracing including exogenous barcodes and endogenous mitochondrial DNA mutations confirmed the reprogramming procession. Although the small chemical compound inhibiting spliceosome function only induces the differentiated hematopoietic progenitors to acquire plasticity and reprograms them into multipotent progenitors but not stem cells so far, this study still provides a proof-of-concept strategy for generating HSCs based on combining two independent steps together in future, first differentiating rare HSCs into large number of progenitors then reprogramming these progenitors into huge number of HSCs. Further dissecting the mechanism underlying spliceosome inhibitor-induced human hematopoietic cell reprogramming in future will help us comprehensively understanding not only the chemical reprogramming to generate desirable human cells for clinical translation but also hematopoiesis under physiological and pathological conditions. Cell reprogramming (dpeaa)DE-He213 Human hematopoietic stem/progenitor cells (dpeaa)DE-He213 Spliceosome (dpeaa)DE-He213 Small molecule compound (dpeaa)DE-He213 Lineage tracing (dpeaa)DE-He213 Wei, Chuijin aut Xiong, Shumin aut Yu, Ping aut Zhou, Ren aut Cheng, Lin aut Enthalten in Experimental hematology & oncology London : Biomed Central, 2012 11(2022), 1 vom: 10. Juni (DE-627)718833341 (DE-600)2669066-4 2162-3619 nnns volume:11 year:2022 number:1 day:10 month:06 https://dx.doi.org/10.1186/s40164-022-00288-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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_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 11 2022 1 10 06
allfieldsSound	10.1186/s40164-022-00288-9 doi (DE-627)SPR050776371 (SPR)s40164-022-00288-9-e DE-627 ger DE-627 rakwb eng Dong, Liaoliao verfasserin aut Spliceosome inhibitor induces human hematopoietic progenitor cell reprogramming toward stemness 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Abstract The application of hematopoietic stem cells (HSCs) has been restricted due to limited cell sources and conventional methods for generating these cells by cell expansion and pluripotent stem cell differentiation have not been clinically achieved. Cell reprogramming technique provides a new hope for generating desirable cells. We previously reported that mouse differentiated hematopoietic cell reprogramming could be induced by small molecule compounds to generate hematopoietic stem/progenitor-like cells, whether the human hematopoietic cells could also be reprogrammed into HSCs by chemical compounds remains elusive. Here, we demonstrated for the first time that human committed hematopoietic progenitors could be reprogrammed into multipotent progenitors by spliceosome inhibitor. Combination of single cell RNA-sequencing and genetic lineage tracing including exogenous barcodes and endogenous mitochondrial DNA mutations confirmed the reprogramming procession. Although the small chemical compound inhibiting spliceosome function only induces the differentiated hematopoietic progenitors to acquire plasticity and reprograms them into multipotent progenitors but not stem cells so far, this study still provides a proof-of-concept strategy for generating HSCs based on combining two independent steps together in future, first differentiating rare HSCs into large number of progenitors then reprogramming these progenitors into huge number of HSCs. Further dissecting the mechanism underlying spliceosome inhibitor-induced human hematopoietic cell reprogramming in future will help us comprehensively understanding not only the chemical reprogramming to generate desirable human cells for clinical translation but also hematopoiesis under physiological and pathological conditions. Cell reprogramming (dpeaa)DE-He213 Human hematopoietic stem/progenitor cells (dpeaa)DE-He213 Spliceosome (dpeaa)DE-He213 Small molecule compound (dpeaa)DE-He213 Lineage tracing (dpeaa)DE-He213 Wei, Chuijin aut Xiong, Shumin aut Yu, Ping aut Zhou, Ren aut Cheng, Lin aut Enthalten in Experimental hematology & oncology London : Biomed Central, 2012 11(2022), 1 vom: 10. Juni (DE-627)718833341 (DE-600)2669066-4 2162-3619 nnns volume:11 year:2022 number:1 day:10 month:06 https://dx.doi.org/10.1186/s40164-022-00288-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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_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 11 2022 1 10 06
language	English
source	Enthalten in Experimental hematology & oncology 11(2022), 1 vom: 10. Juni volume:11 year:2022 number:1 day:10 month:06
sourceStr	Enthalten in Experimental hematology & oncology 11(2022), 1 vom: 10. Juni volume:11 year:2022 number:1 day:10 month:06
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Cell reprogramming Human hematopoietic stem/progenitor cells Spliceosome Small molecule compound Lineage tracing
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container_title	Experimental hematology & oncology
authorswithroles_txt_mv	Dong, Liaoliao @@aut@@ Wei, Chuijin @@aut@@ Xiong, Shumin @@aut@@ Yu, Ping @@aut@@ Zhou, Ren @@aut@@ Cheng, Lin @@aut@@
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author	Dong, Liaoliao
spellingShingle	Dong, Liaoliao misc Cell reprogramming misc Human hematopoietic stem/progenitor cells misc Spliceosome misc Small molecule compound misc Lineage tracing Spliceosome inhibitor induces human hematopoietic progenitor cell reprogramming toward stemness
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topic_title	Spliceosome inhibitor induces human hematopoietic progenitor cell reprogramming toward stemness Cell reprogramming (dpeaa)DE-He213 Human hematopoietic stem/progenitor cells (dpeaa)DE-He213 Spliceosome (dpeaa)DE-He213 Small molecule compound (dpeaa)DE-He213 Lineage tracing (dpeaa)DE-He213
topic	misc Cell reprogramming misc Human hematopoietic stem/progenitor cells misc Spliceosome misc Small molecule compound misc Lineage tracing
topic_unstemmed	misc Cell reprogramming misc Human hematopoietic stem/progenitor cells misc Spliceosome misc Small molecule compound misc Lineage tracing
topic_browse	misc Cell reprogramming misc Human hematopoietic stem/progenitor cells misc Spliceosome misc Small molecule compound misc Lineage tracing
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title	Spliceosome inhibitor induces human hematopoietic progenitor cell reprogramming toward stemness
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title_full	Spliceosome inhibitor induces human hematopoietic progenitor cell reprogramming toward stemness
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author_browse	Dong, Liaoliao Wei, Chuijin Xiong, Shumin Yu, Ping Zhou, Ren Cheng, Lin
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title_sort	spliceosome inhibitor induces human hematopoietic progenitor cell reprogramming toward stemness
title_auth	Spliceosome inhibitor induces human hematopoietic progenitor cell reprogramming toward stemness
abstract	Abstract The application of hematopoietic stem cells (HSCs) has been restricted due to limited cell sources and conventional methods for generating these cells by cell expansion and pluripotent stem cell differentiation have not been clinically achieved. Cell reprogramming technique provides a new hope for generating desirable cells. We previously reported that mouse differentiated hematopoietic cell reprogramming could be induced by small molecule compounds to generate hematopoietic stem/progenitor-like cells, whether the human hematopoietic cells could also be reprogrammed into HSCs by chemical compounds remains elusive. Here, we demonstrated for the first time that human committed hematopoietic progenitors could be reprogrammed into multipotent progenitors by spliceosome inhibitor. Combination of single cell RNA-sequencing and genetic lineage tracing including exogenous barcodes and endogenous mitochondrial DNA mutations confirmed the reprogramming procession. Although the small chemical compound inhibiting spliceosome function only induces the differentiated hematopoietic progenitors to acquire plasticity and reprograms them into multipotent progenitors but not stem cells so far, this study still provides a proof-of-concept strategy for generating HSCs based on combining two independent steps together in future, first differentiating rare HSCs into large number of progenitors then reprogramming these progenitors into huge number of HSCs. Further dissecting the mechanism underlying spliceosome inhibitor-induced human hematopoietic cell reprogramming in future will help us comprehensively understanding not only the chemical reprogramming to generate desirable human cells for clinical translation but also hematopoiesis under physiological and pathological conditions. © The Author(s) 2022
abstractGer	Abstract The application of hematopoietic stem cells (HSCs) has been restricted due to limited cell sources and conventional methods for generating these cells by cell expansion and pluripotent stem cell differentiation have not been clinically achieved. Cell reprogramming technique provides a new hope for generating desirable cells. We previously reported that mouse differentiated hematopoietic cell reprogramming could be induced by small molecule compounds to generate hematopoietic stem/progenitor-like cells, whether the human hematopoietic cells could also be reprogrammed into HSCs by chemical compounds remains elusive. Here, we demonstrated for the first time that human committed hematopoietic progenitors could be reprogrammed into multipotent progenitors by spliceosome inhibitor. Combination of single cell RNA-sequencing and genetic lineage tracing including exogenous barcodes and endogenous mitochondrial DNA mutations confirmed the reprogramming procession. Although the small chemical compound inhibiting spliceosome function only induces the differentiated hematopoietic progenitors to acquire plasticity and reprograms them into multipotent progenitors but not stem cells so far, this study still provides a proof-of-concept strategy for generating HSCs based on combining two independent steps together in future, first differentiating rare HSCs into large number of progenitors then reprogramming these progenitors into huge number of HSCs. Further dissecting the mechanism underlying spliceosome inhibitor-induced human hematopoietic cell reprogramming in future will help us comprehensively understanding not only the chemical reprogramming to generate desirable human cells for clinical translation but also hematopoiesis under physiological and pathological conditions. © The Author(s) 2022
abstract_unstemmed	Abstract The application of hematopoietic stem cells (HSCs) has been restricted due to limited cell sources and conventional methods for generating these cells by cell expansion and pluripotent stem cell differentiation have not been clinically achieved. Cell reprogramming technique provides a new hope for generating desirable cells. We previously reported that mouse differentiated hematopoietic cell reprogramming could be induced by small molecule compounds to generate hematopoietic stem/progenitor-like cells, whether the human hematopoietic cells could also be reprogrammed into HSCs by chemical compounds remains elusive. Here, we demonstrated for the first time that human committed hematopoietic progenitors could be reprogrammed into multipotent progenitors by spliceosome inhibitor. Combination of single cell RNA-sequencing and genetic lineage tracing including exogenous barcodes and endogenous mitochondrial DNA mutations confirmed the reprogramming procession. Although the small chemical compound inhibiting spliceosome function only induces the differentiated hematopoietic progenitors to acquire plasticity and reprograms them into multipotent progenitors but not stem cells so far, this study still provides a proof-of-concept strategy for generating HSCs based on combining two independent steps together in future, first differentiating rare HSCs into large number of progenitors then reprogramming these progenitors into huge number of HSCs. Further dissecting the mechanism underlying spliceosome inhibitor-induced human hematopoietic cell reprogramming in future will help us comprehensively understanding not only the chemical reprogramming to generate desirable human cells for clinical translation but also hematopoiesis under physiological and pathological conditions. © The Author(s) 2022
collection_details	GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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_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
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title_short	Spliceosome inhibitor induces human hematopoietic progenitor cell reprogramming toward stemness
url	https://dx.doi.org/10.1186/s40164-022-00288-9
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author2	Wei, Chuijin Xiong, Shumin Yu, Ping Zhou, Ren Cheng, Lin
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up_date	2024-07-03T17:42:34.101Z
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Spliceosome inhibitor induces human hematopoietic progenitor cell reprogramming toward stemness

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