Format

Send to

Choose Destination
Cell Stem Cell. 2013 Dec 5;13(6):663-75. doi: 10.1016/j.stem.2013.11.015.

Induction of a human pluripotent state with distinct regulatory circuitry that resembles preimplantation epiblast.

Author information

1
Gene Regulation Laboratory, Genome Institute of Singapore, Singapore 138672, Singapore. Electronic address: chanysw@gis.a-star.edu.sg.

Abstract

Human embryonic stem cells (hESCs) are derived from the inner cell mass of the blastocyst. Despite sharing the common property of pluripotency, hESCs are notably distinct from epiblast cells of the preimplantation blastocyst. Here we use a combination of three small-molecule inhibitors to sustain hESCs in a LIF signaling-dependent hESC state (3iL hESCs) with elevated expression of NANOG and epiblast-enriched genes such as KLF4, DPPA3, and TBX3. Genome-wide transcriptome analysis confirms that the expression signature of 3iL hESCs shares similarities with native preimplantation epiblast cells. We also show that 3iL hESCs have a distinct epigenetic landscape, characterized by derepression of preimplantation epiblast genes. Using genome-wide binding profiles of NANOG and OCT4, we identify enhancers that contribute to rewiring of the regulatory circuitry. In summary, our study identifies a distinct hESC state with defined regulatory circuitry that will facilitate future analysis of human preimplantation embryogenesis and pluripotency.

PMID:
24315441
DOI:
10.1016/j.stem.2013.11.015
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center