Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ATF4 governs functional expansion of hematopoietic stem cells partially via Angptl3 in the fetal liver microenvironment

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE66382 | GEO | 2015/11/20

SECONDARY ACCESSION(S): PRJNA276678

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

ATF4 governs functional expansion of hematopoietic stem cells partially via Angptl3 in the fetal liver microenvironment

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-11-20 | E-GEOD-66382 | biostudies-arrayexpress

ATF4 governs functional expansion of hematopoietic stem cells partially via Angptl3 in the fetal liver microenvironment (array)

Project description:In this study, we demonstrated that deletion of the activating transcription factor 4 (ATF4) resulted in severely impaired HSC expansion in the fetal liver at E12.5 and E15.5. In contrast, generation of the first HSC population in the aorta-gonad-mesonephros region at E11.5 was not significantly affected. Furthermore, the HSC-supporting ability of both endothelial and stromal cells in fetal liver was significantly compromised in the absence of ATF4. Gene profiling using RNA-seq revealed down-regulated expression of a panel of cytokines in ATF4-/- stromal cells, including angiopoietin-like protein 3 (Angptl3) and vascular endothelial growth factor-A (VEGFA). To investigate the molecular pathways of ATF4 in the stromal cells and LSK cells in the fetal liver.

2015-11-20 | E-GEOD-66381 | biostudies-arrayexpress

ATF4 governs functional expansion of hematopoietic stem cells partially via Angptl3 in the fetal liver microenvironment (RNA-Seq)

2015-11-20 | E-GEOD-66380 | biostudies-arrayexpress

ATF4 governs functional expansion of hematopoietic stem cells partially via Angptl3 in the fetal liver microenvironment (array)

2015-11-20 | GSE66381 | GEO

ATF4 governs functional expansion of hematopoietic stem cells partially via Angptl3 in the fetal liver microenvironment (RNA-Seq)

2015-11-20 | GSE66380 | GEO

ATF4 plays a pivotal role in the development of functional hematopoietic stem cells in mouse fetal liver.

Project description:The fetal liver (FL) serves as a predominant site for expansion of functional hematopoietic stem cells (HSCs) during mouse embryogenesis. However, the mechanisms for HSC development in FL remain poorly understood. In this study, we demonstrate that deletion of activating transcription factor 4 (ATF4) significantly impaired hematopoietic development and reduced HSC self-renewal in FL. In contrast, generation of the first HSC population in the aorta-gonad-mesonephros region was not affected. The migration activity of ATF4(-/-) HSCs was moderately reduced. Interestingly, the HSC-supporting ability of both endothelial and stromal cells in FL was significantly compromised in the absence of ATF4. Gene profiling using RNA-seq revealed downregulated expression of a panel of cytokines in ATF4(-/-) stromal cells, including angiopoietin-like protein 3 (Angptl3) and vascular endothelial growth factor A (VEGFA). Addition of Angptl3, but not VEGFA, partially rescued the repopulating defect of ATF4(-/-) HSCs in the culture. Furthermore, chromatin immunoprecipitation assay in conjunction with silencing RNA-mediated silencing and complementary DNA overexpression showed transcriptional control of Angptl3 by ATF4. To summarize, ATF4 plays a pivotal role in functional expansion and repopulating efficiency of HSCs in developing FL, and it acts through upregulating transcription of cytokines such as Angptl3 in the microenvironment.

| S-EPMC4653766 | biostudies-literature

In vitro expansion of fetal liver hematopoietic stem cells.

Project description:Fetal liver hematopoietic stem and progenitor cells (HSPCs) have been considered appropriate for the management of aplastic anemia owing to their proliferative potential. Bone marrow recovery was possible in some cases; the engraftment potential of these cells, however was unsatisfactory, possibly due to the availability of a smaller number of these cells from a single fetus. The present study explores how we can expand fetal liver hematopoietic stem cells under in vitro conditions. We isolated mononuclear cells from fetal liver and hematopoietic stem cells were identified and analyzed by cell surface marker CD34. CD34+ fetal liver HSPCs cells were separated by magnetic cell sorting positive selection method. HSPCs (CD34+) were cultured by using 5 cytokines, stem cell factor (SCF), granulocyte macrophages-colony stimulating factor (GM-CSF), interleukin-6 (IL-6), Fms-related tyrosine kinase 3 (FLT-3) and erythropoietin (EPO), in 4 different combinations along with supplements, in serum-free culture media for 21 days. Cell viability continued to be greater than 90% throughout 21 days of culture. The cells expanded best in a combination of media, supplements and 5 cytokines, namely SCF, FLT-3, IL6, EPO and GM-CSF to yield a large number of total (CD34+ & CD34-) cells. Even though the total number of nucleated cells increased in culture significantly, levels of CD34 antigen expression declined steadily over this period.

| S-EPMC8178329 | biostudies-literature

FLT3L governs the development of partially overlapping hematopoietic lineages in humans and mice (Single cell)

Project description: Not available

| S-BSST1333 | biostudies-other

Fetal hepatic progenitors support long-term expansion of hematopoietic stem cells.

Project description:We have developed a coculture system that establishes DLK(+) fetal hepatic progenitors as the authentic supportive cells for expansion of hematopoietic stem (HSCs) and progenitor cells. In 1-week cultures supplemented with serum and supportive cytokines, both cocultured DLK(+) fetal hepatic progenitors and their conditioned medium supported rapid expansion of hematopoietic progenitors and a small increase in HSC numbers. In 2- and 3-week cultures DLK(+) cells, but not their conditioned medium, continuously and significantly (>20-fold) expanded both hematopoietic stem and progenitor cells. Physical contact between HSCs and DLK(+) cells was crucial to maintaining this long-term expansion. Similar HSC expansion (approximately sevenfold) was achieved in cocultures using a serum-free, low cytokine- containing medium. In contrast, DLK(-) cells are incapable of expanding hematopoietic cells, demonstrating that hepatic progenitors are the principle supportive cells for HSC expansion in the fetal liver.

| S-EPMC3701434 | biostudies-literature

Loss of ATF4 leads to functional aging-like attrition of adult hematopoietic stem cells.

Project description:[Figure: see text].

| S-EPMC8694622 | biostudies-literature