Early hematopoietic fate decisions are independent of bone marrow niche

Abstract

Hematopoietic stem cells (HSCs) reside in specialized bone marrow microenvironments, termed niches, which regulate self-renewal and differentiation through local support programs. Although multiple anatomically distinct niches with unique cellular compositions have been described, it remains unclear to what degree these niches differentially shape HSC fate. In parallel, hematopoietic output is modulated with age, yet it remains unclear if this shift in HSC fate is driven by niche-specific modifications. To address these questions, we applied Multiplexed Error Robust Fluorescence in situ Hybridization to jointly define the cellular and spatial organization of the femoral marrow in young and aged mice. We find that while HSC niches are anatomically and compositionally distinct, stem cell lineage priming is not strongly associated with niche identity consistent with our demonstration that fate-shaping signals are provided redundantly across niches. Moreover, we find that while aging remodels the cellular composition of the marrow, reshapes cellular expression, and alters hematopoietic differentiation, HSC niches are preserved, and HSC fate remains niche agnostic. Together these findings separate anatomical niche identity from early HSC fate decisions and are consistent with a model in which hematopoietic support is distributed across different niche locations rather than partitioned among discrete sites.