Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

RNA-seq of mouse fetal liver endothelial cells, hepatoblasts and mesenchymal stromal cells at embryonic time points E13.5 and E17.5

ABSTRACT: The fetal liver (FL) plays a fundamental role in the ontogeny of the hematopoietic system, by transiently providing a fertile microenvironment for the maturation, proliferation and expansion of fetal hematopoietic progenitors, as well as definitive hematopoietic stem cells (HSCs). Nonetheless, the cellular make up and identity of hematopoietic stem and progenitor cell niches in the FL remain underexplored. Here we employed bulk mRNA-seq to investigate the spatiotemporal dynamics and functional relevance of putative niche cells and HSCs in the FL microenvironment. We find that at peak stages of FL hematopoiesis, pro-hematopoietic cytokines are promiscuously expressed by endothelial, mesenchymal cells and hepatoblasts, which form multicellular consortia that collectively provide unrestricted access to supportive factors throughout the entire tissue. Nevertheless, during peak hematopoietic stages, hepatoblasts are most abundant, express highest levels of growth factors and regulate fetal erythropoiesis and HSC expansion through production of Kit ligand. This highly conducive FL microenvironment is transient and gets rapidly remodeled through hepatoblast differentiation, leading to the downregulation of hematopoietic factors and the contraction of supportive niches, which temporarily coincide with the exit of HSCs towards emergent BM tissues.

INSTRUMENT(S): Illumina HiSeq 4000

ORGANISM(S): Mus musculus

SUBMITTER: Karolina Zielinska

PROVIDER: E-MTAB-15617 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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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

RNA-seq of mouse fetal liver endothelial cells, hepatoblasts and mesenchymal stromal cells at embryonic time points E13.5 and E17.5

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