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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Mar 10, 2018 |
| Title |
PCGF5 is required for neural differentiation of embryonic stem cells [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Polycomb-group proteins are key regulators of the transcriptional programs that maintain stem cell identity and dictate lineage specification. Polycomb repressor complex 1 (PRC1) contains the E3 ligases RING1A/B, which monoubiquitinate lysine 119 at histone H2A (H2AK119ub1) to regulate gene expression. PRC1 has been sub-classified into six major complexes based on the presence of a PCGF subunit. Here, we find that Pcgf5, one of six PCGF paralogs, is an important requirement in the differentiation of mouse embryonic stem cells (mESCs) towards a neural cell fate. Although PCGF5 is not required for mESC self-renewal, its loss blocks mESC neural differentiation by activating the SMAD2/TGF-β signaling pathway. Inhibition of SMAD2/TGF-β signaling or rescue by overexpression of Pcgf5 can restore the capability of mESCs to differentiate towards a neural cell fate. PCGF5 works by stimulating RING1B-dependent H2AK119ub1 both in vitro and in vivo, leading to the suppression of TGF-β signaling genes. PCGF5 loss-of-function prevents the reduction of H2AK119ub1 and H3K27me3 around neural specific genes and keeps them repressed. Our results showed that PCGF5 might function as both a repressor for SMAD2/TGF-β signaling pathway and a facilitator for neural differentiation. Together, our findings reveal a critical context-specific function for PCGF5 in directing PRC1 to control cell fate.
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| Overall design |
Both wild type and Pcgf5-/- mESCs were induced to differentiate in N2B27 medium for 6 days. Then the cells were harvested at day 0 and day 6 after neural differentiation with 2 biological replicates. Total RNAs were collected for either RT-qPCR or RNA sequencing.
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| Contributor(s) |
Yao M, Zhou X, Zhou J, Gong S, Hu G, Li J, Huang K, Lai P, Shi G, Hutchins AP, Sun H, Wang H, Yao H |
| Citation(s) |
29765032 |
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| Submission date |
Feb 21, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Jiajian Zhou |
| E-mail(s) |
zhoujj2013@gmail.com
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| Organization name |
Southern Medical University
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| Department |
Dermatology Hospital
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| Street address |
No. 2 Lujing Road, Yuexiu District,
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| City |
Guangzhou |
| State/province |
Guangdong |
| ZIP/Postal code |
NA |
| Country |
China |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA376147 |
| SRA |
SRP100439 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE95127_RAW.tar |
5.5 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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