Upregulation of nascent mitochondrial biogenesis in mouse hematopoietic stem cells parallels upregulation of CD34 and loss of pluripotency: A potential strategy for reducing oxidative risk in stem cells

Charlie Mantel, Steve Messina-Graham, Hal E. Broxmeyer

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Oxidative damage by reactive oxygen species generated in mitochondria is a potential cause of stem-cell dysregulation. Little is known about how hematopoietic stem cells mitigate/lessen this risk in the face of upregulated mitochondrial biogenesis/function necessary for the energy needs of differentiation and progenitor expansion. Here we report that upregulation of mitochondrial mass in mouse hematopoietic stem cells is closely linked to the appearance of CD34 on their surface, a marker indicating loss of long-term repopulating ability. These mitochondria have low membrane potential initially, but become active before exiting the primitive LSK compartment. Steady-state hematopoiesis perturbed by global expression of SDF-1/CXCL12 transgene causes a shift in ratios of these mitochondrialy-distinct LSK populations. Based on known effects of SDF-1 and signaling by it's receptor, CXCR4, along with finding primitive progenitors with high mitochondrial mass but low activity, we suggest a model of asymmetric self-renewing stem cell division that could lessen stem cell exposure to oxidative damage.

Original languageEnglish (US)
Pages (from-to)2008-2017
Number of pages10
JournalCell Cycle
Volume9
Issue number10
DOIs
StatePublished - May 15 2010

Keywords

  • Asymmetric cell division
  • Asymmetric mitochondrial distribution
  • CD34
  • Hematopoiesis
  • LSK bone marrow cells
  • Mitochondria
  • Mitochondrial mass
  • Mitochondrial membrane potential
  • Oxidative stress
  • Stem cells

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

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