Kit^lo hematopoietic stem cells exhibit distinct lymphoid-primed chromatin landscapes that enhance thymic reconstitution.

ABSTRACT: Hematopoietic stem cells (HSC) with multilineage potential are critical for T cell reconstitution after allogeneic hematopoietic cell transplantation (allo-HCT). The Kit^lo HSC subset is enriched for multipotential precursors, but their T cell potential remains poorly characterized. Using a preclinical allo-HCT mouse model, we demonstrate that Kit^lo HSCs provide superior thymic recovery and T cell reconstitution, resulting in improved immune responses to post-transplant infection. Kit^lo HSCs with augmented bone marrow (BM) lymphopoiesis mitigate age-associated thymic alterations and enhance T cell recovery in middle-aged mice. Mechanistically, chromatin profiling reveals Kit^lo HSCs exhibiting higher activity of lymphoid-specifying transcription fa

SUBMITTER: Elias HK 

PROVIDER: S-EPMC12227609 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature