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

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). Examination of the hematopoietic progenitor and stromal compartments of E16.5, E18.5, P0, and adult bone marrow.