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Sci Rep. 2017 Nov 29;7(1):16543. doi: 10.1038/s41598-017-15187-x.

Reprogramming to pluripotency does not require transition through a primitive streak-like state.

Author information

1
Institute of Neuroanatomy & Developmental Biology (INDB), Eberhard Karls University Tuebingen, Oesterbergstr. 3, 72074, Tuebingen, Germany.
2
Department of Internal Medicine I, University Medical Center Ulm, Albert-Einstein-Allee 23, 89081, Ulm, Germany.
3
Institute of Experimental and Clinical Pharmacology and Toxicology II, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
4
Spemann Graduate School of Biology and Medicine (SGBM), Albert-Ludwigs-University Freiburg, Freiburg, Germany.
5
Faculty of Biology, Schänzlestraße 1, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
6
Institute of Experimental and Clinical Pharmacology and Toxicology II, Faculty of Medicine, University of Freiburg, Freiburg, Germany. sebastian.arnold@pharmakol.uni-freiburg.de.
7
BIOSS Centre of Biological Signalling Studies, Albert-Ludwigs-University, Freiburg, Germany. sebastian.arnold@pharmakol.uni-freiburg.de.
8
Department of Internal Medicine I, University Medical Center Ulm, Albert-Einstein-Allee 23, 89081, Ulm, Germany. alexander.kleger@uni-ulm.de.
9
Institute of Neuroanatomy & Developmental Biology (INDB), Eberhard Karls University Tuebingen, Oesterbergstr. 3, 72074, Tuebingen, Germany. stefan.liebau@uni-tuebingen.de.

Abstract

Pluripotency can be induced in vitro from adult somatic mammalian cells by enforced expression of defined transcription factors regulating and initiating the pluripotency network. Despite the substantial advances over the last decade to improve the efficiency of direct reprogramming, exact mechanisms underlying the conversion into the pluripotent stem cell state are still vaguely understood. Several studies suggested that induced pluripotency follows reversed embryonic development. For somatic cells of mesodermal and endodermal origin that would require the transition through a Primitive streak-like state, which would necessarily require an Eomesodermin (Eomes) expressing intermediate. We analyzed reprogramming in human and mouse cells of mesodermal as well as ectodermal origin by thorough marker gene analyses in combination with genetic reporters, conditional loss of function and stable fate-labeling for the broad primitive streak marker Eomes. We unambiguously demonstrate that induced pluripotency is not dependent on a transient primitive streak-like stage and thus does not represent reversal of mesendodermal development in vivo.

PMID:
29185460
PMCID:
PMC5707390
DOI:
10.1038/s41598-017-15187-x
[Indexed for MEDLINE]
Free PMC Article

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