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Divisional History Identifies Differential Precursor Contributions in Native and Perturbed Hematopoiesis and Reveals Functionally Distinct Stem Cell Subsets

ABSTRACT: To uphold appropriate homeostasis of short-lived blood cells, immature blood cells need to proliferate vigorously. Here, using a conditional H2B-mCherry labeling mouse-model, we characterize hematopoietic stem cell (HSC) and progenitor proliferation dynamics in steady state, upon physiological aging and following several types of induced stress. Following transplantation, HSCs shifted towards higher degrees of proliferation that was sustained long-term. HSCs were, by contrast, poorly recruited into proliferation following cytokine-induced mobilization and after acute depletions of selected blood cell lineages. Using indexed single cell sorting coupled to multiplex gene expression analyses, proliferation history separated candidate HSCs into units with distinct molecular and functional attributes. Our data thereby highlight that HSC proliferation following transplantation is fundamentally different not only from native hematopoiesis but also from other stress contexts, and demonstrate the power of divisional history as a functional criterion to resolve HSC heterogeneity.

ORGANISM(S): Mus musculus

PROVIDER: GSE77477 | GEO | 2016/03/18

SECONDARY ACCESSION(S): PRJNA310606

REPOSITORIES: GEO

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