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Cord blood-derived CD34+ hematopoietic cells with low levels of mitochondrial mass are enriched in hematopoietic repopulating stem cell function.
MedLine Citation:
PMID:  23349299     Owner:  NLM     Status:  Publisher    
BACKGROUND. The homeostasis of the hematopoietic stem/progenitor cell pool relies on a fine-tuned balance between self-renewal, differentiation and proliferation. Recent studies have proposed that mitochondria regulate these processes. Although recent work has contributed to understand the role of mitochondria during stem cell differentiation, it remains elusive whether the mitochondrial content/function impacts human hematopoietic stem versus progenitor function. DESIGN AND METHODS. We report that mitochondrial mass highly correlates with mitochondrial membrane potential in CD34+ hematopoietic stem/progenitor cells. Therefore, cord blood CD34+ cells were sorted based on their mitochondrial mass, and the in vitro homeostasis and clonogenic potential as well as the in vivo repopulating potential of CD34+ cells with high (CD34+ MitoHigh) versus low (CD34+ MitoLow) mitochondrial mass was analyzed. RESULTS. CD34+ MitoLow fraction contains 6-fold higher numbers of CD34+CD38- primitive cells, and is enriched in hematopoietic stem cell function as demonstrated by its significantly higher hematopoietic reconstitution potential in immunedeficient mice. In contrast, the CD34+ MitoHigh fraction is more enriched in hematopoietic progenitor function with higher in vitro clonogenic capacity. In vitro differentiation of CD34+ MitoLow cells is significantly delayed as compared to CD34+ MitoHigh cells. The eventual complete differentiation of CD34+ MitoLow cells, which coincides with a robust expansion of the CD34- differentiated progeny, is accompanied by a mitochondrial adaptation as shown by a significant increase in ATP production and expression of the mitochondrial genes ND1 and COX2. CONCLUSIONS. Cord blood CD34+ cells with low levels of mitochondrial mass are enriched in hematopoietic repopulating stem cell function whereas high levels of mitochondrial mass identify hematopoietic progenitors. A mitochondrial response underlies hematopoietic stem/progenitor cell differentiation and proliferation of lineage-committed CD34- cells.
Damia Romero-Moya; Clara Bueno; Rosa Montes; Oscar Navarro-Montero; Francisco J Iborra; Luis Carlos López; Miguel Martin; Pablo Menendez
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-24
Journal Detail:
Title:  Haematologica     Volume:  -     ISSN:  1592-8721     ISO Abbreviation:  Haematologica     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0417435     Medline TA:  Haematologica     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Granada, Spain;
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