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

Trent D. Hall, Hyunjin Kim, Mahmoud Dabbah, Jacquelyn A. Myers, Jeremy Chase Crawford, Antonio Morales-Hernandez, Claire E. Caprio, Pramika Sriram, Emilia Kooienga, Marta Derecka, Esther A. Obeng, Paul G. Thomas and Shannon McKinney-Freeman ()
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Trent D. Hall: St. Jude Children’s Research Hospital
Hyunjin Kim: St. Jude Children’s Research Hospital
Mahmoud Dabbah: St. Jude Children’s Research Hospital
Jacquelyn A. Myers: St. Jude Children’s Research Hospital
Jeremy Chase Crawford: St. Jude Children’s Research Hospital
Antonio Morales-Hernandez: St. Jude Children’s Research Hospital
Claire E. Caprio: St. Jude Children’s Research Hospital
Pramika Sriram: St. Jude Children’s Research Hospital
Emilia Kooienga: St. Jude Children’s Research Hospital
Marta Derecka: St. Jude Children’s Research Hospital
Esther A. Obeng: St. Jude Children’s Research Hospital
Paul G. Thomas: St. Jude Children’s Research Hospital
Shannon McKinney-Freeman: St. Jude Children’s Research Hospital

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract While adult bone marrow (BM) hematopoietic stem and progenitor cells (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 during development. Here, we functionally interrogate murine BM HSPCs from E15.5 through P0. Our work reveals that fetal BM HSPCs are present by E15.5, but distinct from the HSPC pool seen in fetal liver, both phenotypically and functionally, until near birth. We also generate a transcriptional atlas of perinatal BM HSPCs and the BM niche in mice across ontogeny, revealing that fetal BM lacks HSPCs with robust intrinsic stem cell programs, as well as niche cells supportive of HSPCs. In contrast, stem cell programs are preserved in neonatal BM HSPCs, which reside in a niche expressing HSC supportive factors distinct from those seen in adults. Collectively, our results provide important insights into the factors shaping hematopoiesis during this understudied window of hematopoietic development.

Date: 2022
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DOI: 10.1038/s41467-022-33092-4

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