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Murine fetal bone marrow does not support functional hematopoietic stem and progenitor cells until birth

ABSTRACT: Fetal hematopoietic stem and progenitor cells (HSPCs) migrate from fetal liver (FL) to bone marrow (BM) around birth. While adult BM HSPCs and their extrinsic regulation is well studied, little is known about the composition, function, and extrinsic regulation of the first HSPCs to enter the BM. Here, we show that HSPCs colonize multiple fetal bones by E15.5, shift from an MPP2 to an MPP3/4-dominant phenotype by birth, and display little function until E18.5, relative to their FL counterparts. We establish a transcriptional atlas of single perinatal HSPCs, and their putative BM niches, from E15.5 through P0 and show that early fetal BM (FBM) lacks HSPCs with intrinsic stem cell programs and niche cells supportive of HSPCs. In contrast, stem cell programs are preserved in neonatal BM HSPCs, which engage with a niche expressing HSC supportive factors distinct from those seen in adult BM (i.e., IGF).

ORGANISM(S): Mus musculus

PROVIDER: GSE178951 | GEO | 2021/06/26

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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Murine fetal bone marrow does not support functional hematopoietic stem and progenitor cells until birth

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