Clonal-level Lineage Commitment Pathways of Hematopoietic Stem Cells in Vivo

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2019 Jan 10

PMID 30622181

Citations 51

Authors

Rong Lu

Agnieszka Czechowicz

Jun Seita

Du Jiang

Irving L Weissman

Affiliations

Soon will be listed here.

Abstract

While the aggregate differentiation of the hematopoietic stem cell (HSC) population has been extensively studied, little is known about the lineage commitment process of individual HSC clones. Here, we provide lineage commitment maps of HSC clones under homeostasis and after perturbations of the endogenous hematopoietic system. Under homeostasis, all donor-derived HSC clones regenerate blood homogeneously throughout all measured stages and lineages of hematopoiesis. In contrast, after the hematopoietic system has been perturbed by irradiation or by an antagonistic anti-ckit antibody, only a small fraction of donor-derived HSC clones differentiate. Some of these clones dominantly expand and exhibit lineage bias. We identified the cellular origins of clonal dominance and lineage bias and uncovered the lineage commitment pathways that lead HSC clones to different levels of self-renewal and blood production under various transplantation conditions. This study reveals surprising alterations in HSC fate decisions directed by conditioning and identifies the key hematopoiesis stages that may be manipulated to control blood production and balance.

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