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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Harvard University
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cell- och molekylärbiologi
Originalspråkengelska
Sidor (från-till)2809-2818
Antal sidor10
TidskriftCell Reports
Volym14
Utgivningsnummer12
StatusPublished - 2016
PublikationskategoriForskning
Peer review utfördJa

Relaterad forskningsoutput

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

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

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