Mitotic History Reveals Distinct Stem Cell Populations and Their Contributions to Hematopoiesis

Research output: Contribution to journalArticle

Abstract

Homeostasis of short-lived blood cells is dependent on rapid proliferation of immature precursors. Using a conditional histone 2B-mCherry-labeling mouse model, we characterize hematopoietic stem cell (HSC) and progenitor proliferation dynamics in steady state and following several types of induced stress. HSC proliferation following HSC transplantation into lethally irradiated mice is fundamentally different not only from native hematopoiesis but also from other stress contexts. Whereas transplantation promoted sustained, long-term proliferation of HSCs, both cytokine-induced mobilization and acute depletion of selected blood cell lineages elicited very limited recruitment of HSCs to the proliferative pool. By coupling mCherry-based analysis of proliferation history with multiplex gene expression analyses on single cells, we have found that HSCs can be stratified into four distinct subtypes. These subtypes have distinct molecular signatures and differ significantly in their reconstitution potentials, showcasing the power of tracking proliferation history when resolving functional heterogeneity of HSCs.

Details

Authors
Organisations
External organisations
  • Harvard University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
Original languageEnglish
Pages (from-to)2809-2818
Number of pages10
JournalCell Reports
Volume14
Issue number12
Publication statusPublished - 2016
Publication categoryResearch
Peer-reviewedYes

Related research output

Petter Säwén, 2017 Oct 6, Lund: Lund University, Faculty of Medicine.

Research output: ThesisDoctoral Thesis (compilation)

View all (1)