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Cell Rep. 2016 Mar 29;14(12):2809-18. doi: 10.1016/j.celrep.2016.02.073. Epub 2016 Mar 17.

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

Author information

1
Division of Molecular Hematology, Department of Laboratory Medicine, Medical Faculty, Lund University, Klinikgatan 26, BMC B12, 22184 Lund, Sweden.
2
Division of Molecular Hematology, Department of Laboratory Medicine, Medical Faculty, Lund University, Klinikgatan 26, BMC B12, 22184 Lund, Sweden; StemTherapy, Lund University, 22184 Lund, Sweden; Lund Stem Cell Center, Lund University, 22184 Lund, Sweden.
3
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Division of Hematology/Oncology, Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02116, USA.
4
Division of Molecular Hematology, Department of Laboratory Medicine, Medical Faculty, Lund University, Klinikgatan 26, BMC B12, 22184 Lund, Sweden; Hemato-Linné, Lund University, 22184 Lund, Sweden; StemTherapy, Lund University, 22184 Lund, Sweden; Lund Stem Cell Center, Lund University, 22184 Lund, Sweden. Electronic address: david.bryder@med.lu.se.

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.

PMID:
26997272
PMCID:
PMC4819906
DOI:
10.1016/j.celrep.2016.02.073
[Indexed for MEDLINE]
Free PMC Article

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