Epiblast stem cell subpopulations represent mouse embryos of distinct pregastrulation stages.
Embryonic stem cells (ESCs) comprise at least two populations of cells with divergent states of pluripotency. Here, we show that epiblast stem cells (EpiSCs) also comprise two distinct cell populations that can be distinguished by the expression of a specific Oct4-GFP marker. These two subpopulations, Oct4-GFP positive and negative EpiSCs, are capable of converting into each other in vitro. Oct4-GFP positive and negative EpiSCs are distinct from ESCs with respect to global gene expression pattern, epigenetic profile, and Oct4 enhancer utilization. Oct4-GFP negative cells share features with cells of the late mouse epiblast and cannot form chimeras. However, Oct4-GFP positive EpiSCs, which only represent a minor EpiSC fraction, resemble cells of the early epiblast and can readily contribute to chimeras. Our findings suggest that the rare ability of EpiSCs to contribute to chimeras is due to the presence of the minor EpiSC fraction representing the early epiblast.
Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany.
Dong Wook
DW
Han
Natalia
N
Tapia
Jin Young
JY
Joo
Boris
B
Greber
Marcos J
MJ
Araúzo-Bravo
Christof
C
Bernemann
Kinarm
K
Ko
Guangming
G
Wu
Martin
M
Stehling
Jeong Tae
JT
Do
Hans R
HR
Schöler
D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D005855:Germ Layers / Q000166:cytology*; D008297:Male; D051379:Mice / Q000196:embryology*; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D050814:Octamer Transcription Factor-3 / Q000032:analysis / Q000235:genetics; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*
D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse