Totipotent Embryonic Stem Cells Arise in Ground-State Culture Conditions
Embryonic stem cells (ESCs) are derived from mammalian embryos during the transition from totipotency, when individual blastomeres can make all lineages, to pluripotency, when they are competent to make only embryonic lineages. ESCs maintained with inhibitors of MEK and GSK3 (2i) are thought to rep...
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doaj-d23bff0687c54c6580d8f25dd12d3d542020-11-25T00:19:05ZengElsevierCell Reports2211-12472013-06-01361945195710.1016/j.celrep.2013.04.034Totipotent Embryonic Stem Cells Arise in Ground-State Culture ConditionsSophie M. Morgani0Maurice A. Canham1Jennifer Nichols2Alexei A. Sharov3Rosa Portero Migueles4Minoru S.H. Ko5Joshua M. Brickman6MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, EH16 4UU Edinburgh, UKMRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, EH16 4UU Edinburgh, UKWellcome Trust Centre for Stem Cell Research, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UKLaboratory of Genetics, National Institute on Aging, NIH Biomedical Research Centre, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224, USAMRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, EH16 4UU Edinburgh, UKLaboratory of Genetics, National Institute on Aging, NIH Biomedical Research Centre, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224, USAMRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, EH16 4UU Edinburgh, UK Embryonic stem cells (ESCs) are derived from mammalian embryos during the transition from totipotency, when individual blastomeres can make all lineages, to pluripotency, when they are competent to make only embryonic lineages. ESCs maintained with inhibitors of MEK and GSK3 (2i) are thought to represent an embryonically restricted ground state. However, we observed heterogeneous expression of the extraembryonic endoderm marker Hex in 2i-cultured embryos, suggesting that 2i blocked development prior to epiblast commitment. Similarly, 2i ESC cultures were heterogeneous and contained a Hex-positive fraction primed to differentiate into trophoblast and extraembryonic endoderm. Single Hex-positive ESCs coexpressed epiblast and extraembryonic genes and contributed to all lineages in chimeras. The cytokine LIF, necessary for ESC self-renewal, supported the expansion of this population but did not directly support Nanog-positive epiblast-like ESCs. Thus, 2i and LIF support a totipotent state comparable to early embryonic cells that coexpress embryonic and extraembryonic determinants. http://www.sciencedirect.com/science/article/pii/S2211124713002167 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sophie M. Morgani Maurice A. Canham Jennifer Nichols Alexei A. Sharov Rosa Portero Migueles Minoru S.H. Ko Joshua M. Brickman |
spellingShingle |
Sophie M. Morgani Maurice A. Canham Jennifer Nichols Alexei A. Sharov Rosa Portero Migueles Minoru S.H. Ko Joshua M. Brickman Totipotent Embryonic Stem Cells Arise in Ground-State Culture Conditions Cell Reports |
author_facet |
Sophie M. Morgani Maurice A. Canham Jennifer Nichols Alexei A. Sharov Rosa Portero Migueles Minoru S.H. Ko Joshua M. Brickman |
author_sort |
Sophie M. Morgani |
title |
Totipotent Embryonic Stem Cells Arise in Ground-State Culture Conditions |
title_short |
Totipotent Embryonic Stem Cells Arise in Ground-State Culture Conditions |
title_full |
Totipotent Embryonic Stem Cells Arise in Ground-State Culture Conditions |
title_fullStr |
Totipotent Embryonic Stem Cells Arise in Ground-State Culture Conditions |
title_full_unstemmed |
Totipotent Embryonic Stem Cells Arise in Ground-State Culture Conditions |
title_sort |
totipotent embryonic stem cells arise in ground-state culture conditions |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2013-06-01 |
description |
Embryonic stem cells (ESCs) are derived from mammalian embryos during the transition from totipotency, when individual blastomeres can make all lineages, to pluripotency, when they are competent to make only embryonic lineages. ESCs maintained with inhibitors of MEK and GSK3 (2i) are thought to represent an embryonically restricted ground state. However, we observed heterogeneous expression of the extraembryonic endoderm marker Hex in 2i-cultured embryos, suggesting that 2i blocked development prior to epiblast commitment. Similarly, 2i ESC cultures were heterogeneous and contained a Hex-positive fraction primed to differentiate into trophoblast and extraembryonic endoderm. Single Hex-positive ESCs coexpressed epiblast and extraembryonic genes and contributed to all lineages in chimeras. The cytokine LIF, necessary for ESC self-renewal, supported the expansion of this population but did not directly support Nanog-positive epiblast-like ESCs. Thus, 2i and LIF support a totipotent state comparable to early embryonic cells that coexpress embryonic and extraembryonic determinants.
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url |
http://www.sciencedirect.com/science/article/pii/S2211124713002167 |
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