Abstract:
:The hematopoietic system is sustained by a rare population of hematopoietic stem cells (HSCs), which emerge during early embryonic development and then reside in the hypoxic niche of the adult bone marrow microenvironment. Although leptin receptor (Lepr)-expressing stromal cells are well-studied as critical regulators of murine hematopoiesis, the biological implications of Lepr expression on HSCs remain largely unexplored. We hypothesized that Lepr+HSCs are functionally different from other HSCs. Using in vitro and in vivo experimental approaches, we demonstrated that Lepr further differentiates SLAM HSCs into two distinct populations; Lepr+HSCs engrafted better than Lepr-HSCs in primary transplant. Compared to Lepr-LSK cells, Lepr+LSK cells were highly enriched for extensively repopulating and self-renewing HSCs. Molecularly, Lepr+HSCs were characterized by a pro-inflammatory transcriptomic profile enriched for Type-I Interferon and Interferon-gamma (IFN-γ) response pathways, which are known to be critical for the emergence of HSCs in the embryo. We conclude that although Lepr+HSCs represent a minor subset of HSCs, they are highly engrafting cells that possess embryonic-like transcriptomic characteristics, and that Lepr can serve as a reliable marker for functional long-term HSCs, which may have potential clinical applicability.
journal_name
Leukemiajournal_title
Leukemiaauthors
Trinh T,Ropa J,Aljoufi A,Cooper S,Sinn A,Srour EF,Broxmeyer HEdoi
10.1038/s41375-020-01079-zsubject
Has Abstractpub_date
2020-11-07 00:00:00eissn
0887-6924issn
1476-5551pii
10.1038/s41375-020-01079-zpub_type
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