Naive Pluripotent Stem Cells Derived Directly from Isolated Cells of the Human Inner Cell Mass
Conventional generation of stem cells from human blastocysts produces a developmentally advanced, or primed, stage of pluripotency. In vitro resetting to a more naive phenotype has been reported. However, whether the reset culture conditions of selective kinase inhibition can enable capture of naive...
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doaj-dffb88be6d4f4f50b7ef44d64e28f6ae2020-11-24T22:51:08ZengElsevierStem Cell Reports2213-67112016-04-016443744610.1016/j.stemcr.2016.02.005Naive Pluripotent Stem Cells Derived Directly from Isolated Cells of the Human Inner Cell MassGe Guo0Ferdinand von Meyenn1Fatima Santos2Yaoyao Chen3Wolf Reik4Paul Bertone5Austin Smith6Jennifer Nichols7Wellcome Trust – Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UKEpigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UKEpigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UKWellcome Trust – Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UKEpigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UKWellcome Trust – Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UKWellcome Trust – Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UKWellcome Trust – Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UKConventional generation of stem cells from human blastocysts produces a developmentally advanced, or primed, stage of pluripotency. In vitro resetting to a more naive phenotype has been reported. However, whether the reset culture conditions of selective kinase inhibition can enable capture of naive epiblast cells directly from the embryo has not been determined. Here, we show that in these specific conditions individual inner cell mass cells grow into colonies that may then be expanded over multiple passages while retaining a diploid karyotype and naive properties. The cells express hallmark naive pluripotency factors and additionally display features of mitochondrial respiration, global gene expression, and genome-wide hypomethylation distinct from primed cells. They transition through primed pluripotency into somatic lineage differentiation. Collectively these attributes suggest classification as human naive embryonic stem cells. Human counterparts of canonical mouse embryonic stem cells would argue for conservation in the phased progression of pluripotency in mammals.http://www.sciencedirect.com/science/article/pii/S2213671116000564 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ge Guo Ferdinand von Meyenn Fatima Santos Yaoyao Chen Wolf Reik Paul Bertone Austin Smith Jennifer Nichols |
spellingShingle |
Ge Guo Ferdinand von Meyenn Fatima Santos Yaoyao Chen Wolf Reik Paul Bertone Austin Smith Jennifer Nichols Naive Pluripotent Stem Cells Derived Directly from Isolated Cells of the Human Inner Cell Mass Stem Cell Reports |
author_facet |
Ge Guo Ferdinand von Meyenn Fatima Santos Yaoyao Chen Wolf Reik Paul Bertone Austin Smith Jennifer Nichols |
author_sort |
Ge Guo |
title |
Naive Pluripotent Stem Cells Derived Directly from Isolated Cells of the Human Inner Cell Mass |
title_short |
Naive Pluripotent Stem Cells Derived Directly from Isolated Cells of the Human Inner Cell Mass |
title_full |
Naive Pluripotent Stem Cells Derived Directly from Isolated Cells of the Human Inner Cell Mass |
title_fullStr |
Naive Pluripotent Stem Cells Derived Directly from Isolated Cells of the Human Inner Cell Mass |
title_full_unstemmed |
Naive Pluripotent Stem Cells Derived Directly from Isolated Cells of the Human Inner Cell Mass |
title_sort |
naive pluripotent stem cells derived directly from isolated cells of the human inner cell mass |
publisher |
Elsevier |
series |
Stem Cell Reports |
issn |
2213-6711 |
publishDate |
2016-04-01 |
description |
Conventional generation of stem cells from human blastocysts produces a developmentally advanced, or primed, stage of pluripotency. In vitro resetting to a more naive phenotype has been reported. However, whether the reset culture conditions of selective kinase inhibition can enable capture of naive epiblast cells directly from the embryo has not been determined. Here, we show that in these specific conditions individual inner cell mass cells grow into colonies that may then be expanded over multiple passages while retaining a diploid karyotype and naive properties. The cells express hallmark naive pluripotency factors and additionally display features of mitochondrial respiration, global gene expression, and genome-wide hypomethylation distinct from primed cells. They transition through primed pluripotency into somatic lineage differentiation. Collectively these attributes suggest classification as human naive embryonic stem cells. Human counterparts of canonical mouse embryonic stem cells would argue for conservation in the phased progression of pluripotency in mammals. |
url |
http://www.sciencedirect.com/science/article/pii/S2213671116000564 |
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