Murine HSCs contribute actively to native hematopoiesis but with reduced differentiation capacity upon aging

Petter Säwen, Mohamed Eldeeb, Eva Erlandsson, Trine A. Kristiansen, Cecilia Laterza, Zaal Kokaia, Göran Karlsson, Joan Yuan, Shamit Soneji, Pankaj K. Mandal, Derrick J. Rossi, David Bryder

Research output: Contribution to journalArticlepeer-review

27 Citations (SciVal)

Abstract

A hallmark of adult hematopoiesis is the continuous replacement of blood cells with limited lifespans. While active hematopoietic stem cell (HSC) contribution to multilineage hematopoiesis is the foundation of clinical HSC transplantation, recent reports have questioned the physiological contribution of HSCs to normal/steady-state adult hematopoiesis. Here, we use inducible lineage tracing from genetically marked adult HSCs and reveal robust HSC-derived multilineage hematopoiesis. This commences via defined progenitor cells, but varies substantially in between different hematopoietic lineages. By contrast, adult HSC contribution to hematopoietic cells with proposed fetal origins is neglible. Finally, we establish that the HSC contribution to multilineage hematopoiesis declines with increasing age. Therefore, while HSCs are active contributors to native adult hematopoiesis, it appears that the numerical increase of HSCs is a physiologically relevant compensatory mechanism to account for their reduced differentiation capacity with age.

Original languageEnglish
Article numbere41258
JournaleLife
Volume7
DOIs
Publication statusPublished - 2018 Dec 18

Subject classification (UKÄ)

  • Cell and Molecular Biology
  • Hematology

Keywords

  • aging
  • hematopoiesis
  • lineage tracing
  • mouse
  • regenerative medicine
  • steady state
  • stem cells

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