HNF4A Regulates the Formation of Hepatic Progenitor Cells from Human iPSC-Derived Endoderm by Facilitating Efficient Recruitment of RNA Pol II

Elucidating the molecular basis of cell differentiation will advance our understanding of organ development and disease. We have previously established a protocol that efficiently produces cells with hepatocyte characteristics from human induced pluripotent stem cells. We previously used this cell d...

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Bibliographic Details
Published in:Genes 2018-12, Vol.10 (1), p.21
Main Authors: DeLaForest, Ann, Di Furio, Francesca, Jing, Ran, Ludwig-Kubinski, Amy, Twaroski, Kirk, Urick, Amanda, Pulakanti, Kirthi, Rao, Sridhar, Duncan, Stephen A
Format: Article
Language:English
Subjects:
Cell differentiation
Chromatin
DNA sequencing
DNA-directed RNA polymerase
Endoderm
Enzymes
Gene expression
Hepatocyte nuclear factor 4
Immunoprecipitation
Liver
Molecular modelling
Pluripotency
Progenitor cells
Proteins
Recruitment
RNA polymerase
Stem cells
Transcription factors
Transcriptomes
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Summary:Elucidating the molecular basis of cell differentiation will advance our understanding of organ development and disease. We have previously established a protocol that efficiently produces cells with hepatocyte characteristics from human induced pluripotent stem cells. We previously used this cell differentiation model to identify the transcription factor hepatocyte nuclear factor 4 α (HNF4A) as being essential during the transition of the endoderm to a hepatic fate. Here, we sought to define the molecular mechanisms through which HNF4A controls this process. By combining HNF4A chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) analyses at the onset of hepatic progenitor cell formation with transcriptome data collected during early stages of differentiation, we identified genes whose expression is directly dependent upon HNF4A. By examining the dynamic changes that occur at the promoters of these HNF4A targets we reveal that HNF4A is essential for recruitment of RNA polymerase (RNA pol) II to genes that are characteristically expressed as the hepatic progenitors differentiate from the endoderm.
ISSN:2073-4425
2073-4425
DOI:10.3390/genes10010021