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LIM domain binding protein 1 regulates a transcriptional program essential for hematopoietic stem cell maintenance

ABSTRACT: We used ChIP-Seq to map Ldb1, Scl and Gata2 binding sites in mouse hematopoietic progenitor cells (HPCs). Together with functional studies using conventional and conditional Ldb1 deficient mouse models and bioinformatics analysis, we systematically determined a transcriptional program controlled by Ldb1 complexes in HSC maintenance.

ORGANISM(S): Mus musculus

PROVIDER: GSE26031 | GEO | 2011/01/04

SECONDARY ACCESSION(S): PRJNA135497

REPOSITORIES: GEO

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LIM domain binding protein 1 regulates a transcriptional program essential for hematopoietic stem cell maintenance

Project description:We used ChIP-Seq to map Ldb1, Scl and Gata2 binding sites in mouse hematopoietic progenitor cells (HPCs). Together with functional studies using conventional and conditional Ldb1 deficient mouse models and bioinformatics analysis, we systematically determined a transcriptional program controlled by Ldb1 complexes in HSC maintenance. To evaluate the role of Ldb1 in hematopoietic stem cell maintenance.

2011-01-04 | E-GEOD-26031 | biostudies-arrayexpress

Functional and molecular characterization of mouse Gata2-independent hematopoietic progenitors

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

Functional and molecular characterization of mouse Gata2-independent hematopoietic progenitors

2015-12-22 | GSE76254 | GEO

Ldb1-nucleated transcription complexes function as primary mediators of erythroid gene activation

Project description:We used ChIP-Seq to map Ldb1, Scl and Gata1 binding sites in mouse total bone marrow cells. Together with functional studies comparing gene expression in Murine Erythroleukemia (MEL) cells expressing Ldb1 shRNA or control shRNA and bioinformatics analysis, we systematically determined the transcriptional program controlled by Ldb1 complexes in erythropoiesis. This represents the ChIP-Seq component of the study only

2013-04-29 | GSE42843 | GEO

LIM-Domain-Binding 1 maintains the terminally-differentiated state of pancreatic β-cells

Project description:Utilize high-throughput transcriptomic and cistromic analysis to determine the functional requirement for LDB1 and ISL1 in mature murine pancreatic β-cells while simultaneously assessing their functional interdependence at the chromatin level.

2016-12-31 | GSE84759 | GEO

Ldb1-nucleated transcription complexes function as primary mediators of erythroid gene activation

2013-04-29 | E-GEOD-42843 | biostudies-arrayexpress

Overexpression of GATA2 enhances development and maintenance of human embryonic stem cell-derived hematopoietic stem cell-like progenitors

Project description:GATA2 is essential for the endothelial-to-hematopoietic transition (EHT) and generation of hematopoietic stem cells (HSCs). It is poorly understood how GATA2 controls the development of human pluripotent stem cell (hPSC)-derived HSC-like cells. Here, using human embryonic stem cells (hESCs) in which GATA2 overexpression was induced by doxycycline (Dox), we elucidated the dual functions of GATA2 in definitive hematopoiesis before and after the emergence of CD34+CD45+CD90+CD38- HSC-like cells. Specifically, GATA2 promoted expansion of hemogenic precursors via the EHT and then helped to maintain HSC-like cells in a quiescent state by arresting the cell cycle at G0/G1 phase. RNA-sequencing showed that hPSC-derived-HSC-like cells were very similar to human fetal liver-derived HSCs. Our findings will help to elucidate the mechanism that controls the early stages of human definitive hematopoiesis and may help to generate hPSC-derived HSCs.

2019-12-04 | GSE122207 | GEO

GATA2 knockout study to investigated the role of GATA2 in human hematopoiesis

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

Combinatorial Transcriptional Control in Blood Stem/Progenitor Cells: Genome-wide Analysis of 10 major Transcriptional Regulators

Project description:Combinatorial transcription factor (TF) interactions control cellular phenotypes and therefore underpin stem cell formation, maintenance and differentiation. Here we report the genome-wide binding patterns and combinatorial interactions for 10 key regulators of blood stem/progenitor cells (Scl/Tal1, Lyl1, Lmo2, Gata2, Runx1, Meis1, Pu.1, Erg, Fli-1, Gfi1b) thus providing the most comprehensive TF dataset for any adult stem/progenitor cell type to date. Genome-wide computational analysis of complex binding patterns followed by functional validation revealed the following: First, a previously unrecognized combinatorial interaction between a heptad of TFs (Scl, Lyl1, Lmo2, Gata2, Runx1, Erg, Fli-1). Second, we implicate direct protein-protein interactions between four key regulators (Runx1, Gata2, Scl, Erg) in stabilising complex binding to DNA. Third, Runx1+/-::Gata2+/- compound heterozygous mice are not viable with severe haematopoietic defects at midgestation. Taken together, this study demonstrates the power of genome-wide analysis in generating novel functional insights into the transcriptional control of stem and progenitor cells.

2010-10-07 | GSE22178 | GEO

Expression changes in MEL cells upon differentiation and Ldb1 knockdown

Project description:Carbonic anhydrase 1 (Car1), an early specific marker of the erythroid differentiation, has been used to distinguish fetal and adult erythroid cells since its production closely follows the γ- to β-globin transition, but the molecular mechanism underlying transcriptional regulation of Car1 is unclear. Here, we show that Car1 mRNA decreases significantly when erythroid differentiation is induced in MEL cells. The Ldb1 protein complex including GATA1/SCL/LMO2 binds to the Car1 promoter in uninduced cells and reduced enrichment of the complex during differentiation correlates with loss of Car1 expression. Knockdown of Ldb1 results in a reduction of Ser2 phosphorylated RNA Pol II and Cdk9 at the Car1 promoter region, suggesting that Ldb1 is required for recruitment of Pol II as well as the transcription regulator P-TEFb to enhance elongation of Car1 transcripts. Taken together, these data show that Ldb1 forms a regulatory complex to maintain Car1 expression in erythroid cells. Expression analysis of induced and uninduced MEL cells after control or Ldb1 shRNA knockdown.

2012-12-11 | E-GEOD-42839 | biostudies-arrayexpress

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