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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.

ORGANISM(S): Mus musculus

PROVIDER: GSE73641 | GEO | 2016/09/01

SECONDARY ACCESSION(S): PRJNA297493

REPOSITORIES: GEO

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A network including TGFÎ²/Smad4, Gata2 and p57 regulates proliferation of mouse hematopoietic stem/progenitor cells [ChIP-seq]

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2016-09-01 | E-GEOD-73641 | biostudies-arrayexpress

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

Project description: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 early gene targets of TGFβ signaling in hematopoietic progenitor cells, we performed high-throughput gene expression profiling of a primitive murine hematopoietic cell line. One of the revealed target genes was the transcription factor Gata2, which became the base for the rest of the study.

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A network including TGFÎ²/Smad4, Gata2 and p57 regulates proliferation of mouse hematopoietic stem/progenitor cells [expression]

Project description:Transforming growth factor-Î² (TGFÎ²) 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 TGFÎ²-induced Smad signaling in hematopoietic stem and progenitor cells (HSPCs). Interestingly, TGFÎ²-induced Gata2 upregulation is critical for subsequent transcriptional activation of the TGFÎ² 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 early gene targets of TGFÎ² signaling in hematopoietic progenitor cells, we performed high-throughput gene expression profiling of a primitive murine hematopoietic cell line. One of the revealed target genes was the transcription factor Gata2, which became the base for the rest of the study. Three independent RNA harvests were separately analyzed. Untreated cells were used as controls to the 10ng/ml TGFb-treated cells.

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A network including TGFβ/Smad4, Gata2 and p57 regulates proliferation of mouse hematopoietic stem/progenitor cells

Project description:A network including TGFβ/Smad4, Gata2 and p57 regulates proliferation of mouse hematopoietic stem/progenitor cells

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MYCT1 CONTROLS ENVIRONMENTAL SENSING IN HUMAN HEMATOPOIETIC STEM CELLS

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