Population based model of human embryonic stem cell (hESC) differentiation during endoderm induction.

The mechanisms by which human embryonic stem cells (hESC) differentiate to endodermal lineage have not been extensively studied. Mathematical models can aid in the identification of mechanistic information. In this work we use a population-based modeling approach to understand the mechanism of endod...

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Autores principales:	Keith Task, Maria Jaramillo, Ipsita Banerjee
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cb35fb65aea54e1ba5ab03e186c3d294
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spelling	oai:doaj.org-article:cb35fb65aea54e1ba5ab03e186c3d2942021-11-18T07:25:29ZPopulation based model of human embryonic stem cell (hESC) differentiation during endoderm induction.1932-620310.1371/journal.pone.0032975https://doaj.org/article/cb35fb65aea54e1ba5ab03e186c3d2942012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22427920/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The mechanisms by which human embryonic stem cells (hESC) differentiate to endodermal lineage have not been extensively studied. Mathematical models can aid in the identification of mechanistic information. In this work we use a population-based modeling approach to understand the mechanism of endoderm induction in hESC, performed experimentally with exposure to Activin A and Activin A supplemented with growth factors (basic fibroblast growth factor (FGF2) and bone morphogenetic protein 4 (BMP4)). The differentiating cell population is analyzed daily for cellular growth, cell death, and expression of the endoderm proteins Sox17 and CXCR4. The stochastic model starts with a population of undifferentiated cells, wherefrom it evolves in time by assigning each cell a propensity to proliferate, die and differentiate using certain user defined rules. Twelve alternate mechanisms which might describe the observed dynamics were simulated, and an ensemble parameter estimation was performed on each mechanism. A comparison of the quality of agreement of experimental data with simulations for several competing mechanisms led to the identification of one which adequately describes the observed dynamics under both induction conditions. The results indicate that hESC commitment to endoderm occurs through an intermediate mesendoderm germ layer which further differentiates into mesoderm and endoderm, and that during induction proliferation of the endoderm germ layer is promoted. Furthermore, our model suggests that CXCR4 is expressed in mesendoderm and endoderm, but is not expressed in mesoderm. Comparison between the two induction conditions indicates that supplementing FGF2 and BMP4 to Activin A enhances the kinetics of differentiation than Activin A alone. This mechanistic information can aid in the derivation of functional, mature cells from their progenitors. While applied to initial endoderm commitment of hESC, the model is general enough to be applicable either to a system of adult stem cells or later stages of ESC differentiation.Keith TaskMaria JaramilloIpsita BanerjeePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 3, p e32975 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Keith Task Maria Jaramillo Ipsita Banerjee Population based model of human embryonic stem cell (hESC) differentiation during endoderm induction.
description	The mechanisms by which human embryonic stem cells (hESC) differentiate to endodermal lineage have not been extensively studied. Mathematical models can aid in the identification of mechanistic information. In this work we use a population-based modeling approach to understand the mechanism of endoderm induction in hESC, performed experimentally with exposure to Activin A and Activin A supplemented with growth factors (basic fibroblast growth factor (FGF2) and bone morphogenetic protein 4 (BMP4)). The differentiating cell population is analyzed daily for cellular growth, cell death, and expression of the endoderm proteins Sox17 and CXCR4. The stochastic model starts with a population of undifferentiated cells, wherefrom it evolves in time by assigning each cell a propensity to proliferate, die and differentiate using certain user defined rules. Twelve alternate mechanisms which might describe the observed dynamics were simulated, and an ensemble parameter estimation was performed on each mechanism. A comparison of the quality of agreement of experimental data with simulations for several competing mechanisms led to the identification of one which adequately describes the observed dynamics under both induction conditions. The results indicate that hESC commitment to endoderm occurs through an intermediate mesendoderm germ layer which further differentiates into mesoderm and endoderm, and that during induction proliferation of the endoderm germ layer is promoted. Furthermore, our model suggests that CXCR4 is expressed in mesendoderm and endoderm, but is not expressed in mesoderm. Comparison between the two induction conditions indicates that supplementing FGF2 and BMP4 to Activin A enhances the kinetics of differentiation than Activin A alone. This mechanistic information can aid in the derivation of functional, mature cells from their progenitors. While applied to initial endoderm commitment of hESC, the model is general enough to be applicable either to a system of adult stem cells or later stages of ESC differentiation.
format	article
author	Keith Task Maria Jaramillo Ipsita Banerjee
author_facet	Keith Task Maria Jaramillo Ipsita Banerjee
author_sort	Keith Task
title	Population based model of human embryonic stem cell (hESC) differentiation during endoderm induction.
title_short	Population based model of human embryonic stem cell (hESC) differentiation during endoderm induction.
title_full	Population based model of human embryonic stem cell (hESC) differentiation during endoderm induction.
title_fullStr	Population based model of human embryonic stem cell (hESC) differentiation during endoderm induction.
title_full_unstemmed	Population based model of human embryonic stem cell (hESC) differentiation during endoderm induction.
title_sort	population based model of human embryonic stem cell (hesc) differentiation during endoderm induction.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/cb35fb65aea54e1ba5ab03e186c3d294
work_keys_str_mv	AT keithtask populationbasedmodelofhumanembryonicstemcellhescdifferentiationduringendoderminduction AT mariajaramillo populationbasedmodelofhumanembryonicstemcellhescdifferentiationduringendoderminduction AT ipsitabanerjee populationbasedmodelofhumanembryonicstemcellhescdifferentiationduringendoderminduction
_version_	1718423500150013952

Population based model of human embryonic stem cell (hESC) differentiation during endoderm induction.

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