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Analysis of mouse central bone marrow versus endosteal transcriptome to define the hematopoietic stem cell niche at the endosteum

ABSTRACT: Stem cell function is regulated by specialized microenvironments called stem cell niches. These niches maintain stem cells in a dormant state and promote self-renewal. The most potent hematopoietic stem cells (HSC) with high self-renewal potential are reportedly enriched in the endosteal compared to the central region of the bone marrow. Therefore we analyzed the global transcriptome of the endosteal region and directly compared it to that of the central bone marrow (BM). This comparative, differential analysis revealed that in addition to genes specific to the osteoblastic and osteoclastic lineage and classic regulators of HSC (CXCL12, KIT ligand, angiopoietin-1, Jagged-1, N-cadherin), the endosteum abundantly expresses prostaglandin I2 (PGI2) synthase (Ptgis), which produces PGI2. PGI2 is a highly labile, lipid metabolite with no known roles in regulating HSCs. We show in this study that PGI2 is a potent regulator of HSC function. Therefore comparing endosteal versus central BM transcriptome is a viable approach for uncovering candidate genes that may regulate the function of HSC and the HSC niche.

ORGANISM(S): Mus musculus

PROVIDER: GSE25078 | GEO | 2021/08/01

REPOSITORIES: GEO

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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.

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Analysis of mouse central bone marrow versus endosteal transcriptome to define the hematopoietic stem cell niche at the endosteum

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