Similar Datasets
Project description:Innate immune signaling protects against pathogens, controls hematopoietic development and functions in oncogenesis, yet the relationship between these mechanisms is incompletely defined. Downregulating the GATA2 transcription factor in fetal hematopoietic progenitor cells upregulates genes encoding innate immune regulators, increases Interferon-g (IFNg) signaling and disrupts differentiation. Here, we demonstrate that deletion of an enhancer that confers GATA2 expression in fetal progenitor cells elevated Toll-Like Receptor (TLR) TLR1/2 and TLR2/6 expression and signaling. Genetic rescue by expressing GATA2 downregulated the elevated TLR signaling. IFNg amplified TLR1/2 and TLR2/6 signaling in GATA2-deficient progenitor cells, synergistically activating cytokine/chemokine genes and elevating cytokine/chemokine production in their myeloid cell progeny. Genome-wide analysis of how IFNg and TLR signaling remodels the progenitor cell transcriptome in GATA2-deficient cells revealed exaggerated responses at innate immune genes harboring motifs for signal-dependent transcription factors. Thus, GATA2 establishes a transcriptome that constrains innate immune signaling, and insufficient GATA2 renders fetal progenitor cells hypersensitive to innate immune signaling.
2023-04-15 | GSE218445 | GEO
Project description:We generated homozygous GATA2 knockout human embryonic stem cells (GATA2-/- hESCs) and analyzed their blood differentiation potential. Paritcularly at the hemogenic endothelium (HE) stage and hematopoietic progenitor cell (HPC) stage. Our result revealed that GATA2-/- hESCs displayed attenuated generation of CD34+CD43+ HPCs, due to the impairment of endothelial to hematopoietic transition (EHT). However, GATA2-/- hESCs retained the potential to generate erythroblasts, macrophages, but never granulocytes. Through RNA-Seq and further rescue experiment, we further identified that SPI1 was responsible for the defect of GATA2-/- hESCs in generation of CD34+CD43+ HPCs and granulocytes.
2017-02-09 | GSE69797 | GEO
Project description:The Gata2 transcription factor is a pivotal regulator of hematopoietic stem cell (HSC) development and maintenance. Gata2 functions in the embryo during endothelial cell to hematopoietic cell transition (EHT) to affect hematopoietic cluster, HPC and HSC formation. Although previous studies of cell populations phenotypically enriched in HPCs and HSCs show expression of Gata2, there has been no direct study of Gata2 expressing cells during normal hematopoiesis. In this study we generate a Gata2 Venus reporter mouse model with unperturbed Gata2 expression to examine the hematopoietic function and transcriptome of Gata2 expressing and nonexpressing cells. Gata2Venus- HPCs 1 replicate, Gata2Venus+ HPCs 1 replicate
2015-12-22 | E-GEOD-76254 | biostudies-arrayexpress
Project description:We compared single-cell transcriptomes of fetal liver myeloid progenitor pools (CMP/GMP pool) from Gata2 -77 enhancer mutant embryos and wildtype littermates. Gene expression patterns in -77-deficient mice demonstrated loss of erythroid, megakaryocyte and granulocyte progenitors and an increase in monocyte
2020-06-03 | GSE134439 | GEO
Project description:The Gata2 transcription factor is a pivotal regulator of hematopoietic stem cell (HSC) development and maintenance. Gata2 functions in the embryo during endothelial cell to hematopoietic cell transition (EHT) to affect hematopoietic cluster, HPC and HSC formation. Although previous studies of cell populations phenotypically enriched in HPCs and HSCs show expression of Gata2, there has been no direct study of Gata2 expressing cells during normal hematopoiesis. In this study we generate a Gata2 Venus reporter mouse model with unperturbed Gata2 expression to examine the hematopoietic function and transcriptome of Gata2 expressing and nonexpressing cells.
2015-12-22 | GSE76254 | GEO
Project description:In vertebrates, GATA2 is a master regulator of hematopoiesis and is expressed throughout embryo development and in adult life. Although the essential role of GATA2 in mouse hematopoiesis is well established, its involvement during early human hematopoietic development is not clear. By combining time-controlled overexpression of GATA2 with genetic knockout experiments, we found that GATA2, at the mesoderm specification stage, promotes the generation of hemogenic endothelial progenitors and their further differentiation to hematopoietic progenitor cells, and negatively regulates cardiac differentiation. Surprisingly, genome-wide transcriptional and chromatin immunoprecipitation analysis showed that GATA2 bound preferentially to regulatory regions, and repressed the expression of cardiac development-related genes. By contrast, genes important for hematopoietic differentiation were upregulated by GATA2 in a mostly indirect manner. Collectively, our data reveal a hitherto unrecognized role of GATA2 as repressor of cardiac fates, and highlight the importance of coordinating the specification and repression of alternative cell fates.
2019-07-25 | GSE118980 | GEO
Project description:In vertebrates, GATA2 is a master regulator of hematopoiesis and is expressed throughout embryo development and in adult life. Although the essential role of GATA2 for the onset of mouse hematopoiesis is well established, its involvement during early human hematopoietic development is not clear. By combining time-controlled overexpression of GATA2 with genetic knockout experiments, we found that GATA2, at the mesoderm specification stage, promotes the generation of hemogenic progenitors and their further differentiation to hematopoietic progenitor cells, while negatively regulating cardiac differentiation. Surprisingly, genome-wide transcriptional and chromatin immunoprecipitation analysis showed that GATA2 bound preferentially to regulatory regions, and repressed the expression of cardiac development-related genes. By contrast, genes important for hematopoietic differentiation were upregulated by GATA2 in a mostly indirect manner. Collectively, our data reveal a hitherto unrecognized role of GATA2 as a direct repressor of cardiac fates, and highlight the importance of coordinating the specification and repression of alternative cell fates.
2019-07-09 | GSE133996 | 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. 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:Gata2, a zinc finger TF, is essential for the generation and survival of HSCs in the embryo and has been implicated in the pathogenesis of AML, yet the requirement for Gata2 in adult HSCs and LSCs remains unclear. Using a conditional mouse model where Gata2 was deleted specifically in hematopoietic cells, we show that knockout of Gata2 leads to a rapid and complete cell-autonomous loss of adult HSCs. We then performed RNA-seq in sorted HSCs (LSK CD48- CD150+) from control and Gata2+/fl;Vav-iCre+ 8-to-10-week old mice.
2019-06-25 | GSE133248 | GEO