A network including TGFβ/Smad4, Gata2 and p57 regulates proliferation of mouse hematopoietic stem/progenitor cells
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ABSTRACT:
PROVIDER: PRJNA297471 | ENA |
REPOSITORIES: ENA
Dataset's files
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| SRR2542345.fastq.gz | Fastqsanger.gz |
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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 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.
2016-09-01 | GSE73641 | GEO
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.
2016-09-01 | GSE73567 | GEO
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 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.
2016-09-01 | E-GEOD-73641 | biostudies-arrayexpress
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. Three independent RNA harvests were separately analyzed. Untreated cells were used as controls to the 10ng/ml TGFb-treated cells.
2016-09-01 | E-GEOD-73567 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-09-01 | GSE73642 | GEO
Project description:A network including TGFβ/Smad4, Gata2 and p57 regulates proliferation of mouse hematopoietic stem/progenitor cells [expression]
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Project description:To analyze p57 function in mouse fetal liver, we surgically isolated mesothelial and submesothelial cells from E17 p57-/- and p57+/+ livers.
2014-10-01 | GSE61010 | GEO
Project description:A network including TGFβ/Smad4, Gata2 and p57 regulates proliferation of mouse hematopoietic stem/progenitor cells [ChIP-seq]
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Project description:TGFβ is known to be a potent inducer of EMT, a process involved in tumor invasion. TIF1γ has been reported to participate to TGFβ signaling. In order to understand the role of TIF1γ in TGFβ signaling and its requirement for EMT, we analyzed the TGFβ1 response of human mammary epithelial cell lines. A strong EMT increase was observed in TIF1γ-silenced cells after TGFβ1 treatment, whereas Smad4 inactivation completely blocked this process. In support of these observations, microarray data show that the functions of several TIF1γ target genes can be linked to EMT. As a negative regulator of Smad4, TIF1γ could be critical for the regulation of TGFβ signaling. This work highlights the molecular relationship between TIF1γ and Smad4 in TGFβ1 signaling and EMT. Total mRNA extractions were performed for 11 samples from transfected HMEC-TR. Replicates are rimo1, 6; rimo3, 9; rimo2, 7; rimo 4, 10 and rimo 5, 11. Rimo 8 is a single experiment. All RNA extractions were obtained from two independent cell cultures excepted for rimo8. Rimo 1, 6 are replicate for ctrl-; Rimo 3, 9 are replicate for ctrl+; Rimo 2, 7 are replicate for SiTIF-; Rimo 4, 10 are replicate for SiTIF+; Rimo8 is SiSmad4-; and Rimo5, 11 are replicate for SiSmad4+. ctrl means that HMEC-TR were transfected with an SiRNA scramble. "siSmad4" means that HMEC-TR were transfected with an SiRNA anti Smad4. "siTIF" means that HMEC-TR were transfected with an SiRNA anti TIF1γ. "-" means that cells were grown without TGFβ. "+" means that cells were treated with 5 ng/ml TGFβ1 for 24h.
2011-05-26 | E-GEOD-28448 | biostudies-arrayexpress
Project description:RNA-sequencing of TGFβ treated empty vector (EV) or Smad4-expressing AKPS lines followed by GSEA revealed a number of gene sets overlapping with those obtained from analyses in reactive cholangiocytes. Hallmark gene sets MYC, E2F, G2M checkpoint, and oxidative phosphorylation were enriched with loss of Smad4, while TGFβ signaling, EMT, and TNFα were enriched with intact Smad4 signaling, suggesting conserved growth suppressive functions of Smad4 in primary cholangiocytes and advanced cancer.
2023-12-07 | GSE237679 | GEO