Induction of pluripotency in human somatic cells via a transient state resembling primitive streak-like mesendoderm

During mammalian embryonic development, the primitive streak initiates the differentiation of pluripotent epiblast cells into germ layers. Pluripotency can be reacquired in committed somatic cells using a combination of a handful of transcription factors, such as OCT3/4, SOX2, KLF4 and c-MYC (hereaf...

Full description

Saved in:
Bibliographic Details
Published in:Nature communications 2014-04, Vol.5 (1), p.3678-3678, Article 3678
Main Authors: Takahashi, Kazutoshi, Tanabe, Koji, Ohnuki, Mari, Narita, Megumi, Sasaki, Aki, Yamamoto, Masamichi, Nakamura, Michiko, Sutou, Kenta, Osafune, Kenji, Yamanaka, Shinya
Format: Article
Language:English
Subjects:
13/100
631/136/2086
631/136/2444
Cell Differentiation - physiology
Cells, Cultured
Endoderm - cytology
Humanities and Social Sciences
Humans
Mesoderm - cytology
multidisciplinary
Pluripotent Stem Cells - cytology
Science
Science (multidisciplinary)
Transcription Factors - physiology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:During mammalian embryonic development, the primitive streak initiates the differentiation of pluripotent epiblast cells into germ layers. Pluripotency can be reacquired in committed somatic cells using a combination of a handful of transcription factors, such as OCT3/4, SOX2, KLF4 and c-MYC (hereafter referred to as OSKM), albeit with low efficiency. Here we show that during OSKM-induced reprogramming towards pluripotency in human cells, intermediate cells transiently show gene expression profiles resembling mesendoderm, which is a major component of the primitive streak. Based on these findings, we discover that forkhead box H1 (FOXH1), a transcription factor required for anterior primitive streak specification during early development, significantly enhances the reprogramming efficiency of human fibroblasts by promoting their maturation, including mesenchymal to epithelial transition and the activation of late pluripotency markers. These results demonstrate that during the reprogramming process, human somatic cells go through a transient state that resembles mesendoderm. The mesendoderm is located in the embryonic primitive streak's anterior region, which is specified by the transcription factor FOXH1. Here, the authors show that human fibroblasts transit through a mesendoderm-like state during reprogramming into pluripotent cells, and that expression of FOXH1 enhances reprogramming efficiency.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms4678