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.
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.
Mantel
Charlie
C
Department of Microbiology and Immunology, Indiana University School of Medicine; Indianapolis, IN, USA. cmantel@iupui.edu
Messina-Graham
Steve
S
Broxmeyer
Hal E
HE
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D018384:Oxidative Stress / Q000502:physiology; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism
D018952:Antigens, CD34; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4