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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| Veröffentlicht in: | PLoS computational biology 2021-03, Vol.17 (3), p.e1008778-e1008778 |
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| creator | Brown, Jared Barry, Christopher Schmitz, Matthew T Argus, Cara Bolin, Jennifer M Schwartz, Michael P Van Aartsen, Amy Steill, John Swanson, Scott Stewart, Ron Thomson, James A Kendziorski, Christina |
| 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. |
| doi_str_mv | 10.1371/journal.pcbi.1008778 |
| format | Article |
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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.</description><identifier>ISSN: 1553-7358</identifier><identifier>ISSN: 1553-734X</identifier><identifier>EISSN: 1553-7358</identifier><identifier>DOI: 10.1371/journal.pcbi.1008778</identifier><identifier>PMID: 33647016</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Biology and Life Sciences ; Cell culture ; Cell cycle ; Cell differentiation ; Comparative analysis ; Correlation analysis ; Data analysis ; Differentiation ; Gene expression ; Genetic aspects ; Identification and classification ; Methods ; Microscopy ; Neurogenesis ; Neurons ; Pluripotency ; Quality control ; Regenerative medicine ; Regression analysis ; Research and Analysis Methods ; Ribonucleic acid ; RNA ; Segmentation ; Stem cell research ; Stem cell transplantation ; Stem cells ; Transcriptomes ; Trends</subject><ispartof>PLoS computational biology, 2021-03, Vol.17 (3), p.e1008778-e1008778</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Brown et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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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.</description><subject>Biology and Life Sciences</subject><subject>Cell culture</subject><subject>Cell cycle</subject><subject>Cell differentiation</subject><subject>Comparative analysis</subject><subject>Correlation analysis</subject><subject>Data analysis</subject><subject>Differentiation</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Identification and classification</subject><subject>Methods</subject><subject>Microscopy</subject><subject>Neurogenesis</subject><subject>Neurons</subject><subject>Pluripotency</subject><subject>Quality control</subject><subject>Regenerative medicine</subject><subject>Regression analysis</subject><subject>Research and Analysis Methods</subject><subject>Ribonucleic 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cells</atitle><jtitle>PLoS computational biology</jtitle><addtitle>PLoS Comput Biol</addtitle><date>2021-03</date><risdate>2021</risdate><volume>17</volume><issue>3</issue><spage>e1008778</spage><epage>e1008778</epage><pages>e1008778-e1008778</pages><issn>1553-7358</issn><issn>1553-734X</issn><eissn>1553-7358</eissn><abstract>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. 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| subjects | Biology and Life Sciences Cell culture Cell cycle Cell differentiation Comparative analysis Correlation analysis Data analysis Differentiation Gene expression Genetic aspects Identification and classification Methods Microscopy Neurogenesis Neurons Pluripotency Quality control Regenerative medicine Regression analysis Research and Analysis Methods Ribonucleic acid RNA Segmentation Stem cell research Stem cell transplantation Stem cells Transcriptomes Trends |
| title | Interspecies chimeric conditions affect the developmental rate of human pluripotent stem cells |
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