Direct Induction of the Three Pre-implantation Blastocyst Cell Types from Fibroblasts.
Animals
Blastocyst
/ physiology
Cell Differentiation
Cell Lineage
Cells, Cultured
Cellular Reprogramming
Embryo Implantation
Endoderm
/ physiology
Fibroblasts
/ physiology
Induced Pluripotent Stem Cells
/ physiology
Mice
Receptors, Estrogen
/ genetics
T-Box Domain Proteins
/ genetics
Transcription Factors
/ metabolism
Trophoblasts
/ physiology
Eomes
Esrrb
early embryonic development
induced extraembryonic endoderm stem cells
induced pluripotent stem cells
induced trophoblast stem cells
inner cell mass
primitive endoderm
reprogramming
trophectoderm
Journal
Cell stem cell
ISSN: 1875-9777
Titre abrégé: Cell Stem Cell
Pays: United States
ID NLM: 101311472
Informations de publication
Date de publication:
06 06 2019
06 06 2019
Historique:
received:
25
04
2018
revised:
03
01
2019
accepted:
22
03
2019
pubmed:
30
4
2019
medline:
22
7
2020
entrez:
30
4
2019
Statut:
ppublish
Résumé
Following fertilization, totipotent cells undergo asymmetric cell divisions, resulting in three distinct cell types in the late pre-implantation blastocyst: epiblast (Epi), primitive endoderm (PrE), and trophectoderm (TE). Here, we aim to understand whether these three cell types can be induced from fibroblasts by one combination of transcription factors. By utilizing a sophisticated fluorescent knockin reporter system, we identified a combination of five transcription factors, Gata3, Eomes, Tfap2c, Myc, and Esrrb, that can reprogram fibroblasts into induced pluripotent stem cells (iPSCs), induced trophoblast stem cells (iTSCs), and induced extraembryonic endoderm stem cells (iXENs), concomitantly. In-depth transcriptomic, chromatin, and epigenetic analyses provide insights into the molecular mechanisms that underlie the reprogramming process toward the three cell types. Mechanistically, we show that the interplay between Esrrb and Eomes during the reprogramming process determines cell fate, where high levels of Esrrb induce a XEN-like state that drives pluripotency and high levels of Eomes drive trophectodermal fate.
Identifiants
pubmed: 31031139
pii: S1934-5909(19)30117-1
doi: 10.1016/j.stem.2019.03.018
pmc: PMC6561721
pii:
doi:
Substances chimiques
EOMES protein, human
0
ESRRB protein, human
0
Receptors, Estrogen
0
T-Box Domain Proteins
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
983-994.e7Subventions
Organisme : Howard Hughes Medical Institute
ID : 55008727
Pays : United States
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
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