Genomics

Dataset Information

236

A network including TGFβ/Smad4, Gata2 and p57 regulates proliferation of mouse hematopoietic stem/progenitor cells [ChIP-seq]


ABSTRACT: Transforming growth factor-β (TGFβ) is a potent inhibitor of hematopoietic stem cell (HSC) proliferation. However, the precise mechanism for this effect is unknown. Here, we have identified the transcription factor Gata2, previously described as an important regulator of HSC function, as an early and direct target gene for TGFβ-induced Smad signaling in hematopoietic stem and progenitor cells (HSPCs). Interestingly, TGFβ-induced Gata2 upregulation is critical for subsequent transcriptional activation of the TGFβ signaling effector molecule p57 and resulting growth arrest of HSPCs. Importantly, both Gata2 and p57 are abundantly expressed in freshly isolated highly purified HSCs, demonstrating the relevance of this circuit in HSC regulation within the HSC niche. Our results connect key molecules involved in HSC self-renewal and reveal a functionally relevant network regulating proliferation of primitive hematopoietic cells. To identify TGFβ targets downstream of Gata2, we carried out a ChIP-Seq experiment on TGFβ-induced Lhx2 cells. Interestingly, there was a large overlap between the GATA2-bound genes and genes differentially expressed after 2h TGFβ induction. One sample of 1x10^8 cells (treated with 10 ng/ml TGFβ for 2h) was sequenced.

ORGANISM(S): Mus musculus  

SUBMITTER: Shamit Soneji   John Brown  Marjo Salminen  Stefan Karlsson  Alex J Tipping  Emma Rorby  Tariq Enver  Matilda Billing  Goran Karlsson 

PROVIDER: E-GEOD-73641 | ArrayExpress | 2016-09-01

SECONDARY ACCESSION(S): SRP064401GSE73641PRJNA297493

REPOSITORIES: GEO, ArrayExpress, ENA

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