Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

SUBMITTER: dan liu

PROVIDER: E-GEOD-66381 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

Zhao Yunze Y Zhou Jie J Liu Dan D Dong Fang F Cheng Hui H Wang Weili W Pang Yakun Y Wang Yajie Y Mu Xiaohuan X Ni Yanli Y Li Zhuan Z Xu Huiyu H Hao Sha S Wang Xiaochen X Ma Shihui S Wang Qian-fei QF Xiao Guozhi G Yuan Weiping W Liu Bing B Cheng Tao T

Blood 20150917 21

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 m ...[more]

PMID: 26384355

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Project description:Hematopoietic stem cells (HSCs) are at the basis of the hematopoietic hierarchy. Their ability to self-renew and differentiate is strictly controlled by molecular signals produced by their surrounding micorenvironments composed of stromal cells. HSCs first emerge in the AGM (Aorta Gonads Mesonephros) region, amplify in the fetal liver (FL) and are maintained in the adult bone marrow (BM). To further characterize the molecular program of the HSC niches, we have compared the global transcriptome of HSC-supportive and non-supportive stromal clones established from the AGM, FL and BM. Hematopoietic stem cells (HSCs) are at the basis of the hematopoietic hierarchy. Their ability to self-renew and differentiate is strictly controlled by molecular signals produced by their surrounding micorenvironments composed of stromal cells. HSCs first emerge in the AGM (Aorta Gonads Mesonephros) region, amplify in the fetal liver (FL) and are maintained in the adult bone marrow (BM). To further characterize the molecular program of the HSC niches, we have compared the global transcriptome of HSC-supportive line from Fetal Calvaria (OP9) and non-supportive stromal clones from fetal liver (BFC). Hematopoietic stem cells (HSCs) are at the basis of the hematopoietic hierarchy. Their ability to self-renew and differentiate is strictly controlled by molecular signals produced by their surrounding micorenvironments composed of stromal cells. HSCs first emerge in the AGM (Aorta Gonads Mesonephros) region, amplify in the fetal liver (FL) and are maintained in the adult bone marrow (BM). To further characterize the molecular program of the HSC niches, we have compared the global transcriptome of HSC-supportive and non-supportive stromal clones established from fetal liver. We took advantage of stromal clones established from the AGM, FL and BM and tested for their ability to support or not HSCs ex vivo. RNA were extracted from confluent stromal cultures or sorted cells and used for hybridization of Affymetrix (mouse gene 1.0 ST) microarrays.

Dataset Information

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

Publications

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

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