Interspecies chimeric conditions affect the developmental rate of human pluripotent stem cells.

Human pluripotent stem cells hold significant promise for regenerative medicine. However, long differentiation protocols and immature characteristics of stem cell-derived cell types remain challenges to the development of many therapeutic applications. In contrast to the slow differentiation of huma...

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Autores principales:	Jared Brown, Christopher Barry, Matthew T Schmitz, Cara Argus, Jennifer M Bolin, Michael P Schwartz, Amy Van Aartsen, John Steill, Scott Swanson, Ron Stewart, James A Thomson, Christina Kendziorski
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c8c89b8e35e94610b7bc51983a0d7e5e
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spelling	oai:doaj.org-article:c8c89b8e35e94610b7bc51983a0d7e5e2021-12-02T19:57:35ZInterspecies chimeric conditions affect the developmental rate of human pluripotent stem cells.1553-734X1553-735810.1371/journal.pcbi.1008778https://doaj.org/article/c8c89b8e35e94610b7bc51983a0d7e5e2021-03-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1008778https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Human pluripotent stem cells hold significant promise for regenerative medicine. However, long differentiation protocols and immature characteristics of stem cell-derived cell types remain challenges to the development of many therapeutic applications. In contrast to the slow differentiation of human stem cells in vitro that mirrors a nine-month gestation period, mouse stem cells develop according to a much faster three-week gestation timeline. Here, we tested if co-differentiation with mouse pluripotent stem cells could accelerate the differentiation speed of human embryonic stem cells. Following a six-week RNA-sequencing time course of neural differentiation, we identified 929 human genes that were upregulated earlier and 535 genes that exhibited earlier peaked expression profiles in chimeric cell cultures than in human cell cultures alone. Genes with accelerated upregulation were significantly enriched in Gene Ontology terms associated with neurogenesis, neuron differentiation and maturation, and synapse signaling. Moreover, chimeric mixed samples correlated with in utero human embryonic samples earlier than human cells alone, and acceleration was dose-dependent on human-mouse co-culture ratios. The altered gene expression patterns and developmental rates described in this report have implications for accelerating human stem cell differentiation and the use of interspecies chimeric embryos in developing human organs for transplantation.Jared BrownChristopher BarryMatthew T SchmitzCara ArgusJennifer M BolinMichael P SchwartzAmy Van AartsenJohn SteillScott SwansonRon StewartJames A ThomsonChristina KendziorskiPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 3, p e1008778 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Jared Brown Christopher Barry Matthew T Schmitz Cara Argus Jennifer M Bolin Michael P Schwartz Amy Van Aartsen John Steill Scott Swanson Ron Stewart James A Thomson Christina Kendziorski Interspecies chimeric conditions affect the developmental rate of human pluripotent stem cells.
description	Human pluripotent stem cells hold significant promise for regenerative medicine. However, long differentiation protocols and immature characteristics of stem cell-derived cell types remain challenges to the development of many therapeutic applications. In contrast to the slow differentiation of human stem cells in vitro that mirrors a nine-month gestation period, mouse stem cells develop according to a much faster three-week gestation timeline. Here, we tested if co-differentiation with mouse pluripotent stem cells could accelerate the differentiation speed of human embryonic stem cells. Following a six-week RNA-sequencing time course of neural differentiation, we identified 929 human genes that were upregulated earlier and 535 genes that exhibited earlier peaked expression profiles in chimeric cell cultures than in human cell cultures alone. Genes with accelerated upregulation were significantly enriched in Gene Ontology terms associated with neurogenesis, neuron differentiation and maturation, and synapse signaling. Moreover, chimeric mixed samples correlated with in utero human embryonic samples earlier than human cells alone, and acceleration was dose-dependent on human-mouse co-culture ratios. The altered gene expression patterns and developmental rates described in this report have implications for accelerating human stem cell differentiation and the use of interspecies chimeric embryos in developing human organs for transplantation.
format	article
author	Jared Brown Christopher Barry Matthew T Schmitz Cara Argus Jennifer M Bolin Michael P Schwartz Amy Van Aartsen John Steill Scott Swanson Ron Stewart James A Thomson Christina Kendziorski
author_facet	Jared Brown Christopher Barry Matthew T Schmitz Cara Argus Jennifer M Bolin Michael P Schwartz Amy Van Aartsen John Steill Scott Swanson Ron Stewart James A Thomson Christina Kendziorski
author_sort	Jared Brown
title	Interspecies chimeric conditions affect the developmental rate of human pluripotent stem cells.
title_short	Interspecies chimeric conditions affect the developmental rate of human pluripotent stem cells.
title_full	Interspecies chimeric conditions affect the developmental rate of human pluripotent stem cells.
title_fullStr	Interspecies chimeric conditions affect the developmental rate of human pluripotent stem cells.
title_full_unstemmed	Interspecies chimeric conditions affect the developmental rate of human pluripotent stem cells.
title_sort	interspecies chimeric conditions affect the developmental rate of human pluripotent stem cells.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/c8c89b8e35e94610b7bc51983a0d7e5e
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Interspecies chimeric conditions affect the developmental rate of human pluripotent stem cells.

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