Murine Fetal Bone Marrow Does Not Support Functional Hematopoietic Stem and Progenitor Cells Until Birth

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Sep 15

PMID 36109585

Authors

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

Shannon McKinney-Freeman

Affiliations

Soon will be listed here.

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.

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