Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

10 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Functional and molecular characterization of mouse Gata2-independent hematopoietic progenitors

ABSTRACT: 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

ORGANISM(S): Mus musculus

SUBMITTER: Elaine Dzierzak

PROVIDER: E-GEOD-76254 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

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.

2015-12-22 | GSE76254 | 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

Transcriptomic analysis of Brm-/- hematopoietic stem and progenitor cells (LSK)

Project description:Little is known of hematopoietic stem (HSC) and progenitor (HPC) cell self-renewal. The role of Brahma (BRM), a chromatin remodeler, in HSC/HPC function is unknown. Bone marrow (BM) from Brm-/- mice manifested increased numbers of long- and short-term HSCs, GMPs, and increased numbers and cycling of functional HPCs. Brm-/- HSC/HPC show demonstrated functional differences compared to wildtype HSC/HPC in vivo and ex vivo, due in part to increased intracellular valine in lineage negative BM. To determine changes in gene programs associated with loss of BRM, we performed RNA sequencing on Brm-/- LSK cells. Brm-/- LSK exhibited upregulated interferon response/cell cycle gene programs, suggesting important extrinsic effects on primitive HSC/HPC from more mature HPC due to the absence of BRM.

2021-11-08 | GSE183430 | GEO

GATA2/eGFP knockin study to trace the endothelial to hematopoietic transition and hematopoietic progenitor cells in human hematopoiesis.

Project description:We generated GATA2/eGFP knockin human embryonic stem cells (H1-GATA2W/eGFP hESCs) and analyzed eGFP expression at different hematopoietic stages, paritcularly the hemogenic endothelium (HE) and hematopoietic progenitor cell (HPC) stage. Our results revealed that, at the HE stage, eGFP expression discriminates authentic HE from non-hematopoietic endothlial cells (EC) and, at the HPC stage, eGFP expression marks the HPC. Further transcriptome comparison analysis revealed distinct characteristics of the HE and EC. Our study provided ideal model to study the EHT and HPC generation, therefore underpining further study on human ESC modeled hematopoiesis.

2017-02-08 | GSE74041 | GEO

Genes differentially expressed in long-term hematopoietic stem cells with latexin deletion [multipotent progenitor cells, MPPs]

Project description:Latexin is a hematopoietic stem cells (HSCs) and progenitor cells (HPCs) regulatory gene. Its deletion leads to the expansion of HSC and HPC population. The underlying mechanims are largely unknown. We therefore perfored microarrary analysis in HPCs with (Lxn-/-) and without (wild-type, WT) latexin deletion, and determined genes that were altered by latexin deletion. This led us to identify the molecular mechanims by which latexin regulates HSC function.

2017-02-09 | GSE94664 | GEO

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.

2016-09-01 | E-GEOD-73567 | biostudies-arrayexpress

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

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 TGFÎ² targets downstream of Gata2, we carried out a ChIP-Seq experiment on TGFÎ²-induced Lhx2 cells. Interestingly, there was a large overlap between the GATA2-bound genes and genes differentially expressed after 2h TGFÎ² induction. One sample of 1x10^8 cells (treated with 10 ng/ml TGFÎ² for 2h) was sequenced.

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

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

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.

2016-09-01 | GSE73567 | GEO

CXCL12/CXCR4 signaling enhances human PSC-derived hematopoietic progenitor function and overcomes early in vivo transplantation failure

Project description:Human pluripotent stem cells (hPSC) generate hematopoietic progenitor cells (HPC), but fail to engraft xenograft models, which is a hallmark feature of adult/somatic hematopoietic stem cells (HSC) from human donors. Progress to derive hPSC-derived HSCs has relied on cell autonomous approaches that force expression of transcription factors (TF), however the role of bone marrow (BM) niche remains poorly understood. Here, we quantified a failure of hPSC-HPCs to survive even in the first 24 h upon transplantation into the BM. Across several hPSC-HPC differentiation methodologies, we identified the lack of CXCR4 expression and network function. Ectopic CXCR4 conferred CXCL12-dependent signaling of hPSC-HPCs in biochemical assays and increased migration/chemotaxis and progenitor capacity, as well as survival and proliferation following transplantation in vivo. In addition, hPSC-HPCs forced to express CXCR4 demonstrated a transcriptional shift toward somatic HPCs, but this approach failed to produce long-term HSC engraftment. Our results reveal that independent of differentiation methods, networks involving CXCR4 should be targeted to generate HSCs with in vivo function from hPSCs.

2018-06-21 | GSE106721 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data