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| Status |
Public on Apr 06, 2020 |
| Title |
TGF-beta couples pluripotency and epithelial character via ZNF398 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Human pluripotent stem cells (hPSCs) have the capacity to give rise to all differentiated cells of the adult. TGF-beta is used routinely for expansion of conventional hPSCs as flat epithelial colonies expressing the transcription factors POU5F1/OCT4, NANOG, SOX2. Here we report a global analysis of the transcriptional program controlled by TGF-beta followed by an unbiased gain-of-function screening in multiple hPSC lines to identify factors mediating TGF-beta activity. We identify a quartet of transcriptional regulators promoting hPSC self-renewal including ZNF398, a human-specific mediator of pluripotency and epithelial character in hPSCs. Mechanistically, ZNF398 binds active promoters and enhancers together with SMAD3 and the histone acetyltransferase EP300, enabling transcription of TGF-beta targets. In the context of somatic cell reprogramming, inhibition of ZNF398 abolishes activation of pluripotency and epithelial genes and iPSC colony formation. Our findings have clear implications for the generation of bona fide hPSCs for regenerative medicine.
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| Overall design |
Stable transgenic hPSCs expressing candidates and SB43 treatment
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| Contributor(s) |
Zorzan I, Pellegrini M, Arboit M, Incarnato D, Maldotti M, Forcato M, Tagliazucchi GM, Carbognin E, Montagner M, Oliviero S, Martello G |
| Citation(s) |
32398665 |
| Submission date |
Jul 01, 2019 |
| Last update date |
Jul 06, 2020 |
| Contact name |
Danny Incarnato |
| E-mail(s) |
d.incarnato@rug.nl
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| Organization name |
University of Groningen
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| Department |
Molecular Genetics
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| Street address |
Nijenborgh 7
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| City |
Groningen |
| State/province |
Netherlands |
| ZIP/Postal code |
9747 AG |
| Country |
Netherlands |
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| Platforms (2) |
| GPL17303 |
Ion Torrent Proton (Homo sapiens) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (30)
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| Relations |
| BioProject |
PRJNA552066 |
| SRA |
SRP212709 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE133630_RAW.tar |
2.2 Gb |
(http)(custom) |
TAR (of BEDGRAPH) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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