Transcriptomics

Dataset Information

6

Reprogramming fibroblasts into bi-potential hepatic stem cells by defined factors


ABSTRACT: Recent studies have demonstrated direct reprogramming of fibroblasts into a range of somatic cell types, but to date stem/progenitor cells have only been reprogrammed for the blood and neuronal lineages. We previously reported generation of induced hepatocyte-like (iHep) cells by transduction of Gata4, Hnf1α, and Foxa3 in p19 Arf null mouse embryonic fibroblasts (MEFs). Here, we show that Hnf1β and Foxa3, liver organogenesis transcription factors, are sufficient to reprogram MEFs into induced hepatic stem cells (iHepSCs). iHepSCs can be stably expanded in vitro and possess the potential of bi-directional differentiation into both hepatocytic and cholangiocytic lineages. In the injured liver of fumarylacetoacetate hydrolase (Fah)-deficient mice, repopulating iHepSCs become hepatocyte-like cells. They also engraft as cholangiocytes into bile ducts of mice with DDC-induced bile ductular injury. Lineage-conversion into bi-potential expandable iHepSCs provides a strategy to enable efficient derivation of both hepatocytes and cholangiocytes for use in disease modeling and tissue engineering. iHepSCs were converted form fibroblasts by transduction of Hnf1β and Foxa3. iHepSCs were induced to differentiate into hepatocyte-like cells and cholangiocytes in vitro. Totally, 9 samples including four clones of iHepSCS, one clone of LEPCs, two samples of MEFs and two samples of iHepSCs-derived cholangocytes were analyzed.

ORGANISM(S): Mus musculus  

SUBMITTER: Pu You   Wen-Lin Li  Hai-Ying Zhu  Kirk J Wangensteen  Qing-Wang Han  Dao Xiang  Li-Jian Hui  Chang-Cheng Liu  Xi-Wen Lin  Jian-Xiu Li  Xin Wang  Fei Chen  Yi-Ping Hu  Xiao-Yuan Zi  Yufang Shi  Min-Jun Wang  Uyunbilig Borjigin  Bing Yu  Zhi-Ying He  Chun-Sheng Han 

PROVIDER: E-GEOD-48486 | ArrayExpress | 2013-07-19

SECONDARY ACCESSION(S): GSE48486PRJNA210316

REPOSITORIES: GEO, ArrayExpress

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Publications


Recent studies have demonstrated direct reprogramming of fibroblasts into a range of somatic cell types, but to date stem or progenitor cells have only been reprogrammed for the blood and neuronal lineages. We previously reported generation of induced hepatocyte-like (iHep) cells by transduction of Gata4, Hnf1α, and Foxa3 in p19 Arf null mouse embryonic fibroblasts (MEFs). Here, we show that Hnf1β and Foxa3, liver organogenesis transcription factors, are sufficient to reprogram MEFs into induced  ...[more]

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