Unknown

Dataset Information

0

A sequential EMT-MET mechanism drives the differentiation of human embryonic stem cells towards hepatocytes.

ABSTRACT: Reprogramming has been shown to involve EMT-MET; however, its role in cell differentiation is unclear. We report here that in vitro differentiation of hESCs to hepatic lineage undergoes a sequential EMT-MET with an obligatory intermediate mesenchymal phase. Gene expression analysis reveals that Activin A-induced formation of definitive endoderm (DE) accompanies a synchronous EMT mediated by autocrine TGF? signalling followed by a MET process. Pharmacological inhibition of TGF? signalling blocks the EMT as well as DE formation. We then identify SNAI1 as the key EMT transcriptional factor required for the specification of DE. Genetic ablation of SNAI1 in hESCs does not affect the maintenance of pluripotency or neural differentiation, but completely disrupts the formation of DE. These results reveal a critical mesenchymal phase during the acquisition of DE, highlighting a role for sequential EMT-METs in both differentiation and reprogramming.

SUBMITTER: Li Q 

PROVIDER: S-EPMC5418622 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

A sequential EMT-MET mechanism drives the differentiation of human embryonic stem cells towards hepatocytes.

Li Qiuhong Q   Hutchins Andrew P AP   Chen Yong Y   Li Shengbiao S   Shan Yongli Y   Liao Baojian B   Zheng Dejin D   Shi Xi X   Li Yinxiong Y   Chan Wai-Yee WY   Pan Guangjin G   Wei Shicheng S   Shu Xiaodong X   Pei Duanqing D  

Nature communications 20170503

Reprogramming has been shown to involve EMT-MET; however, its role in cell differentiation is unclear. We report here that in vitro differentiation of hESCs to hepatic lineage undergoes a sequential EMT-MET with an obligatory intermediate mesenchymal phase. Gene expression analysis reveals that Activin A-induced formation of definitive endoderm (DE) accompanies a synchronous EMT mediated by autocrine TGFβ signalling followed by a MET process. Pharmacological inhibition of TGFβ signalling blocks  ...[more]

Similar Datasets

Transcriptomics Differentiation of human embryonic stem cells towards hepatocytes
2017-04-28 | E-GEOD-70741 | biostudies-arrayexpress
Transcriptomics Differentiation of human embryonic stem cells towards hepatocytes
2017-04-28 | GSE70741 | GEO
Unknown Sequential EMT-MET induces neuronal conversion through Sox2.
| S-EPMC5450022 | biostudies-literature
Unknown Differentiation and transplantation of human embryonic stem cell-derived hepatocytes.
| S-EPMC2732349 | biostudies-literature
Unknown ZFP451-mediated SUMOylation of SATB2 drives embryonic stem cell differentiation.
| S-EPMC8336893 | biostudies-literature
Unknown Sequential Differentiation of Embryonic Stem Cells into Neural Epithelial-Like Stem Cells and Oligodendrocyte Progenitor Cells.
| S-EPMC4871441 | biostudies-literature
Unknown DNMT3A-coordinated splicing governs the stem state switch towards differentiation in embryonic and haematopoietic stem cells.
| S-EPMC10337578 | biostudies-literature
Unknown Collagen Type I Improves the Differentiation of Human Embryonic Stem Cells towards Definitive Endoderm.
| S-EPMC4694921 | biostudies-literature
Unknown Differentiation of embryonic stem cells into hepatocytes that coexpress coagulation factors VIII and IX.
| S-EPMC4003324 | biostudies-other
Unknown Changes in glycosaminoglycan structure on differentiation of human embryonic stem cells towards mesoderm and endoderm lineages.
| S-EPMC4004645 | biostudies-literature