Multistable and multistep dynamics in neutrophil differentiation

Background Cell differentiation has long been theorized to represent a switch in a bistable system, and recent experimental work in micro-organisms has revealed bistable dynamics in small gene regulatory circuits. However, the dynamics of mammalian cell differentiation has not been analyzed with res...
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Autor*in:	Chang, Hannah H [verfasserIn] Oh, Philmo Y Ingber, Donald E Huang, Sui

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2006

Schlagwörter:	HL60 Cell Bistable System CD11b Expression DMSO Treatment Bistable Switch

Anmerkung:	© Chang et al; licensee BioMed Central Ltd. 2006. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (

Übergeordnetes Werk:	Enthalten in: BMC cell biology - London : BioMed Central, 2000, 7(2006), 1 vom: 28. Feb.
Übergeordnetes Werk:	volume:7 ; year:2006 ; number:1 ; day:28 ; month:02

Links:	Volltext

DOI / URN:	10.1186/1471-2121-7-11

Katalog-ID:	SPR026932512

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520			\|a Background Cell differentiation has long been theorized to represent a switch in a bistable system, and recent experimental work in micro-organisms has revealed bistable dynamics in small gene regulatory circuits. However, the dynamics of mammalian cell differentiation has not been analyzed with respect to bistability. Results Here we studied how HL60 promyelocytic precursor cells transition to the neutrophil cell lineage after stimulation with the differentiation inducer, dimethyl sulfoxide (DMSO). Single cell analysis of the expression kinetics of the differentiation marker CD11b (Mac-1) revealed all-or-none switch-like behavior, in contrast to the seemingly graduated change of expression when measured as a population average. Progression from the precursor to the differentiated state was detected as a discrete transition between low ($ CD11b^{Low} $) and high ($ CD11b^{High} $) expressor subpopulations distinguishable in a bimodal distribution. Hysteresis in the dependence of CD11b expression on DMSO dose suggests that this bimodality may reflect a bistable dynamic. But when an "unswitched" ($ CD11b^{Low} $) subpopulation of cells in the bistable/bimodal regime was isolated and cultured, these cells were found to differ from undifferentiated precursor cells in that they were "primed" to differentiate. Conclusion These findings indicate that differentiation of human HL60 cells into neutrophils does not result from a simple state transition of a bistable switch as traditionally modeled. Instead, mammalian differentiation appears to be a multi-step process in a high-dimensional system, a result which is consistent with the high connectivity of the cells' complex underlying gene regulatory network.
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matchkey_str	article:14712121:2006----::utsaladutsednmcinurpi
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publishDate	2006
allfields	10.1186/1471-2121-7-11 doi (DE-627)SPR026932512 (SPR)1471-2121-7-11-e DE-627 ger DE-627 rakwb eng Chang, Hannah H verfasserin aut Multistable and multistep dynamics in neutrophil differentiation 2006 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Chang et al; licensee BioMed Central Ltd. 2006. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Cell differentiation has long been theorized to represent a switch in a bistable system, and recent experimental work in micro-organisms has revealed bistable dynamics in small gene regulatory circuits. However, the dynamics of mammalian cell differentiation has not been analyzed with respect to bistability. Results Here we studied how HL60 promyelocytic precursor cells transition to the neutrophil cell lineage after stimulation with the differentiation inducer, dimethyl sulfoxide (DMSO). Single cell analysis of the expression kinetics of the differentiation marker CD11b (Mac-1) revealed all-or-none switch-like behavior, in contrast to the seemingly graduated change of expression when measured as a population average. Progression from the precursor to the differentiated state was detected as a discrete transition between low ($ CD11b^{Low} $) and high ($ CD11b^{High} $) expressor subpopulations distinguishable in a bimodal distribution. Hysteresis in the dependence of CD11b expression on DMSO dose suggests that this bimodality may reflect a bistable dynamic. But when an "unswitched" ($ CD11b^{Low} $) subpopulation of cells in the bistable/bimodal regime was isolated and cultured, these cells were found to differ from undifferentiated precursor cells in that they were "primed" to differentiate. Conclusion These findings indicate that differentiation of human HL60 cells into neutrophils does not result from a simple state transition of a bistable switch as traditionally modeled. Instead, mammalian differentiation appears to be a multi-step process in a high-dimensional system, a result which is consistent with the high connectivity of the cells' complex underlying gene regulatory network. HL60 Cell (dpeaa)DE-He213 Bistable System (dpeaa)DE-He213 CD11b Expression (dpeaa)DE-He213 DMSO Treatment (dpeaa)DE-He213 Bistable Switch (dpeaa)DE-He213 Oh, Philmo Y aut Ingber, Donald E aut Huang, Sui aut Enthalten in BMC cell biology London : BioMed Central, 2000 7(2006), 1 vom: 28. Feb. (DE-627)326644830 (DE-600)2041486-9 1471-2121 nnns volume:7 year:2006 number:1 day:28 month:02 https://dx.doi.org/10.1186/1471-2121-7-11 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA 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_70 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 2006 1 28 02
spelling	10.1186/1471-2121-7-11 doi (DE-627)SPR026932512 (SPR)1471-2121-7-11-e DE-627 ger DE-627 rakwb eng Chang, Hannah H verfasserin aut Multistable and multistep dynamics in neutrophil differentiation 2006 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Chang et al; licensee BioMed Central Ltd. 2006. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Cell differentiation has long been theorized to represent a switch in a bistable system, and recent experimental work in micro-organisms has revealed bistable dynamics in small gene regulatory circuits. However, the dynamics of mammalian cell differentiation has not been analyzed with respect to bistability. Results Here we studied how HL60 promyelocytic precursor cells transition to the neutrophil cell lineage after stimulation with the differentiation inducer, dimethyl sulfoxide (DMSO). Single cell analysis of the expression kinetics of the differentiation marker CD11b (Mac-1) revealed all-or-none switch-like behavior, in contrast to the seemingly graduated change of expression when measured as a population average. Progression from the precursor to the differentiated state was detected as a discrete transition between low ($ CD11b^{Low} $) and high ($ CD11b^{High} $) expressor subpopulations distinguishable in a bimodal distribution. Hysteresis in the dependence of CD11b expression on DMSO dose suggests that this bimodality may reflect a bistable dynamic. But when an "unswitched" ($ CD11b^{Low} $) subpopulation of cells in the bistable/bimodal regime was isolated and cultured, these cells were found to differ from undifferentiated precursor cells in that they were "primed" to differentiate. Conclusion These findings indicate that differentiation of human HL60 cells into neutrophils does not result from a simple state transition of a bistable switch as traditionally modeled. Instead, mammalian differentiation appears to be a multi-step process in a high-dimensional system, a result which is consistent with the high connectivity of the cells' complex underlying gene regulatory network. HL60 Cell (dpeaa)DE-He213 Bistable System (dpeaa)DE-He213 CD11b Expression (dpeaa)DE-He213 DMSO Treatment (dpeaa)DE-He213 Bistable Switch (dpeaa)DE-He213 Oh, Philmo Y aut Ingber, Donald E aut Huang, Sui aut Enthalten in BMC cell biology London : BioMed Central, 2000 7(2006), 1 vom: 28. Feb. (DE-627)326644830 (DE-600)2041486-9 1471-2121 nnns volume:7 year:2006 number:1 day:28 month:02 https://dx.doi.org/10.1186/1471-2121-7-11 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA 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_70 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 2006 1 28 02
allfields_unstemmed	10.1186/1471-2121-7-11 doi (DE-627)SPR026932512 (SPR)1471-2121-7-11-e DE-627 ger DE-627 rakwb eng Chang, Hannah H verfasserin aut Multistable and multistep dynamics in neutrophil differentiation 2006 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Chang et al; licensee BioMed Central Ltd. 2006. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Cell differentiation has long been theorized to represent a switch in a bistable system, and recent experimental work in micro-organisms has revealed bistable dynamics in small gene regulatory circuits. However, the dynamics of mammalian cell differentiation has not been analyzed with respect to bistability. Results Here we studied how HL60 promyelocytic precursor cells transition to the neutrophil cell lineage after stimulation with the differentiation inducer, dimethyl sulfoxide (DMSO). Single cell analysis of the expression kinetics of the differentiation marker CD11b (Mac-1) revealed all-or-none switch-like behavior, in contrast to the seemingly graduated change of expression when measured as a population average. Progression from the precursor to the differentiated state was detected as a discrete transition between low ($ CD11b^{Low} $) and high ($ CD11b^{High} $) expressor subpopulations distinguishable in a bimodal distribution. Hysteresis in the dependence of CD11b expression on DMSO dose suggests that this bimodality may reflect a bistable dynamic. But when an "unswitched" ($ CD11b^{Low} $) subpopulation of cells in the bistable/bimodal regime was isolated and cultured, these cells were found to differ from undifferentiated precursor cells in that they were "primed" to differentiate. Conclusion These findings indicate that differentiation of human HL60 cells into neutrophils does not result from a simple state transition of a bistable switch as traditionally modeled. Instead, mammalian differentiation appears to be a multi-step process in a high-dimensional system, a result which is consistent with the high connectivity of the cells' complex underlying gene regulatory network. HL60 Cell (dpeaa)DE-He213 Bistable System (dpeaa)DE-He213 CD11b Expression (dpeaa)DE-He213 DMSO Treatment (dpeaa)DE-He213 Bistable Switch (dpeaa)DE-He213 Oh, Philmo Y aut Ingber, Donald E aut Huang, Sui aut Enthalten in BMC cell biology London : BioMed Central, 2000 7(2006), 1 vom: 28. Feb. (DE-627)326644830 (DE-600)2041486-9 1471-2121 nnns volume:7 year:2006 number:1 day:28 month:02 https://dx.doi.org/10.1186/1471-2121-7-11 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA 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_70 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 2006 1 28 02
allfieldsGer	10.1186/1471-2121-7-11 doi (DE-627)SPR026932512 (SPR)1471-2121-7-11-e DE-627 ger DE-627 rakwb eng Chang, Hannah H verfasserin aut Multistable and multistep dynamics in neutrophil differentiation 2006 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Chang et al; licensee BioMed Central Ltd. 2006. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Cell differentiation has long been theorized to represent a switch in a bistable system, and recent experimental work in micro-organisms has revealed bistable dynamics in small gene regulatory circuits. However, the dynamics of mammalian cell differentiation has not been analyzed with respect to bistability. Results Here we studied how HL60 promyelocytic precursor cells transition to the neutrophil cell lineage after stimulation with the differentiation inducer, dimethyl sulfoxide (DMSO). Single cell analysis of the expression kinetics of the differentiation marker CD11b (Mac-1) revealed all-or-none switch-like behavior, in contrast to the seemingly graduated change of expression when measured as a population average. Progression from the precursor to the differentiated state was detected as a discrete transition between low ($ CD11b^{Low} $) and high ($ CD11b^{High} $) expressor subpopulations distinguishable in a bimodal distribution. Hysteresis in the dependence of CD11b expression on DMSO dose suggests that this bimodality may reflect a bistable dynamic. But when an "unswitched" ($ CD11b^{Low} $) subpopulation of cells in the bistable/bimodal regime was isolated and cultured, these cells were found to differ from undifferentiated precursor cells in that they were "primed" to differentiate. Conclusion These findings indicate that differentiation of human HL60 cells into neutrophils does not result from a simple state transition of a bistable switch as traditionally modeled. Instead, mammalian differentiation appears to be a multi-step process in a high-dimensional system, a result which is consistent with the high connectivity of the cells' complex underlying gene regulatory network. HL60 Cell (dpeaa)DE-He213 Bistable System (dpeaa)DE-He213 CD11b Expression (dpeaa)DE-He213 DMSO Treatment (dpeaa)DE-He213 Bistable Switch (dpeaa)DE-He213 Oh, Philmo Y aut Ingber, Donald E aut Huang, Sui aut Enthalten in BMC cell biology London : BioMed Central, 2000 7(2006), 1 vom: 28. Feb. (DE-627)326644830 (DE-600)2041486-9 1471-2121 nnns volume:7 year:2006 number:1 day:28 month:02 https://dx.doi.org/10.1186/1471-2121-7-11 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA 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_70 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 2006 1 28 02
allfieldsSound	10.1186/1471-2121-7-11 doi (DE-627)SPR026932512 (SPR)1471-2121-7-11-e DE-627 ger DE-627 rakwb eng Chang, Hannah H verfasserin aut Multistable and multistep dynamics in neutrophil differentiation 2006 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Chang et al; licensee BioMed Central Ltd. 2006. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Cell differentiation has long been theorized to represent a switch in a bistable system, and recent experimental work in micro-organisms has revealed bistable dynamics in small gene regulatory circuits. However, the dynamics of mammalian cell differentiation has not been analyzed with respect to bistability. Results Here we studied how HL60 promyelocytic precursor cells transition to the neutrophil cell lineage after stimulation with the differentiation inducer, dimethyl sulfoxide (DMSO). Single cell analysis of the expression kinetics of the differentiation marker CD11b (Mac-1) revealed all-or-none switch-like behavior, in contrast to the seemingly graduated change of expression when measured as a population average. Progression from the precursor to the differentiated state was detected as a discrete transition between low ($ CD11b^{Low} $) and high ($ CD11b^{High} $) expressor subpopulations distinguishable in a bimodal distribution. Hysteresis in the dependence of CD11b expression on DMSO dose suggests that this bimodality may reflect a bistable dynamic. But when an "unswitched" ($ CD11b^{Low} $) subpopulation of cells in the bistable/bimodal regime was isolated and cultured, these cells were found to differ from undifferentiated precursor cells in that they were "primed" to differentiate. Conclusion These findings indicate that differentiation of human HL60 cells into neutrophils does not result from a simple state transition of a bistable switch as traditionally modeled. Instead, mammalian differentiation appears to be a multi-step process in a high-dimensional system, a result which is consistent with the high connectivity of the cells' complex underlying gene regulatory network. HL60 Cell (dpeaa)DE-He213 Bistable System (dpeaa)DE-He213 CD11b Expression (dpeaa)DE-He213 DMSO Treatment (dpeaa)DE-He213 Bistable Switch (dpeaa)DE-He213 Oh, Philmo Y aut Ingber, Donald E aut Huang, Sui aut Enthalten in BMC cell biology London : BioMed Central, 2000 7(2006), 1 vom: 28. Feb. (DE-627)326644830 (DE-600)2041486-9 1471-2121 nnns volume:7 year:2006 number:1 day:28 month:02 https://dx.doi.org/10.1186/1471-2121-7-11 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA 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_70 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 2006 1 28 02
language	English
source	Enthalten in BMC cell biology 7(2006), 1 vom: 28. Feb. volume:7 year:2006 number:1 day:28 month:02
sourceStr	Enthalten in BMC cell biology 7(2006), 1 vom: 28. Feb. volume:7 year:2006 number:1 day:28 month:02
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	HL60 Cell Bistable System CD11b Expression DMSO Treatment Bistable Switch
isfreeaccess_bool	true
container_title	BMC cell biology
authorswithroles_txt_mv	Chang, Hannah H @@aut@@ Oh, Philmo Y @@aut@@ Ingber, Donald E @@aut@@ Huang, Sui @@aut@@
publishDateDaySort_date	2006-02-28T00:00:00Z
hierarchy_top_id	326644830
id	SPR026932512
language_de	englisch
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author	Chang, Hannah H
spellingShingle	Chang, Hannah H misc HL60 Cell misc Bistable System misc CD11b Expression misc DMSO Treatment misc Bistable Switch Multistable and multistep dynamics in neutrophil differentiation
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topic_title	Multistable and multistep dynamics in neutrophil differentiation HL60 Cell (dpeaa)DE-He213 Bistable System (dpeaa)DE-He213 CD11b Expression (dpeaa)DE-He213 DMSO Treatment (dpeaa)DE-He213 Bistable Switch (dpeaa)DE-He213
topic	misc HL60 Cell misc Bistable System misc CD11b Expression misc DMSO Treatment misc Bistable Switch
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title	Multistable and multistep dynamics in neutrophil differentiation
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title_full	Multistable and multistep dynamics in neutrophil differentiation
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author_browse	Chang, Hannah H Oh, Philmo Y Ingber, Donald E Huang, Sui
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author-letter	Chang, Hannah H
doi_str_mv	10.1186/1471-2121-7-11
title_sort	multistable and multistep dynamics in neutrophil differentiation
title_auth	Multistable and multistep dynamics in neutrophil differentiation
abstract	Background Cell differentiation has long been theorized to represent a switch in a bistable system, and recent experimental work in micro-organisms has revealed bistable dynamics in small gene regulatory circuits. However, the dynamics of mammalian cell differentiation has not been analyzed with respect to bistability. Results Here we studied how HL60 promyelocytic precursor cells transition to the neutrophil cell lineage after stimulation with the differentiation inducer, dimethyl sulfoxide (DMSO). Single cell analysis of the expression kinetics of the differentiation marker CD11b (Mac-1) revealed all-or-none switch-like behavior, in contrast to the seemingly graduated change of expression when measured as a population average. Progression from the precursor to the differentiated state was detected as a discrete transition between low ($ CD11b^{Low} $) and high ($ CD11b^{High} $) expressor subpopulations distinguishable in a bimodal distribution. Hysteresis in the dependence of CD11b expression on DMSO dose suggests that this bimodality may reflect a bistable dynamic. But when an "unswitched" ($ CD11b^{Low} $) subpopulation of cells in the bistable/bimodal regime was isolated and cultured, these cells were found to differ from undifferentiated precursor cells in that they were "primed" to differentiate. Conclusion These findings indicate that differentiation of human HL60 cells into neutrophils does not result from a simple state transition of a bistable switch as traditionally modeled. Instead, mammalian differentiation appears to be a multi-step process in a high-dimensional system, a result which is consistent with the high connectivity of the cells' complex underlying gene regulatory network. © Chang et al; licensee BioMed Central Ltd. 2006. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
abstractGer	Background Cell differentiation has long been theorized to represent a switch in a bistable system, and recent experimental work in micro-organisms has revealed bistable dynamics in small gene regulatory circuits. However, the dynamics of mammalian cell differentiation has not been analyzed with respect to bistability. Results Here we studied how HL60 promyelocytic precursor cells transition to the neutrophil cell lineage after stimulation with the differentiation inducer, dimethyl sulfoxide (DMSO). Single cell analysis of the expression kinetics of the differentiation marker CD11b (Mac-1) revealed all-or-none switch-like behavior, in contrast to the seemingly graduated change of expression when measured as a population average. Progression from the precursor to the differentiated state was detected as a discrete transition between low ($ CD11b^{Low} $) and high ($ CD11b^{High} $) expressor subpopulations distinguishable in a bimodal distribution. Hysteresis in the dependence of CD11b expression on DMSO dose suggests that this bimodality may reflect a bistable dynamic. But when an "unswitched" ($ CD11b^{Low} $) subpopulation of cells in the bistable/bimodal regime was isolated and cultured, these cells were found to differ from undifferentiated precursor cells in that they were "primed" to differentiate. Conclusion These findings indicate that differentiation of human HL60 cells into neutrophils does not result from a simple state transition of a bistable switch as traditionally modeled. Instead, mammalian differentiation appears to be a multi-step process in a high-dimensional system, a result which is consistent with the high connectivity of the cells' complex underlying gene regulatory network. © Chang et al; licensee BioMed Central Ltd. 2006. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
abstract_unstemmed	Background Cell differentiation has long been theorized to represent a switch in a bistable system, and recent experimental work in micro-organisms has revealed bistable dynamics in small gene regulatory circuits. However, the dynamics of mammalian cell differentiation has not been analyzed with respect to bistability. Results Here we studied how HL60 promyelocytic precursor cells transition to the neutrophil cell lineage after stimulation with the differentiation inducer, dimethyl sulfoxide (DMSO). Single cell analysis of the expression kinetics of the differentiation marker CD11b (Mac-1) revealed all-or-none switch-like behavior, in contrast to the seemingly graduated change of expression when measured as a population average. Progression from the precursor to the differentiated state was detected as a discrete transition between low ($ CD11b^{Low} $) and high ($ CD11b^{High} $) expressor subpopulations distinguishable in a bimodal distribution. Hysteresis in the dependence of CD11b expression on DMSO dose suggests that this bimodality may reflect a bistable dynamic. But when an "unswitched" ($ CD11b^{Low} $) subpopulation of cells in the bistable/bimodal regime was isolated and cultured, these cells were found to differ from undifferentiated precursor cells in that they were "primed" to differentiate. Conclusion These findings indicate that differentiation of human HL60 cells into neutrophils does not result from a simple state transition of a bistable switch as traditionally modeled. Instead, mammalian differentiation appears to be a multi-step process in a high-dimensional system, a result which is consistent with the high connectivity of the cells' complex underlying gene regulatory network. © Chang et al; licensee BioMed Central Ltd. 2006. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
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title_short	Multistable and multistep dynamics in neutrophil differentiation
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Multistable and multistep dynamics in neutrophil differentiation

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