title: Mitochondrial DNA sequence heterogeneity of single CD34+ cells after nonmyeloablative allogeneic stem cell transplantation.
abstract: We applied a single-cell method to detect mitochondrial DNA (mtDNA) mutations to evaluate the reconstitution of hematopoietic stem cells (HSCs) and committed progenitor cells after nonmyeloablative allogeneic stem cell transplantation in humans. In a total of 1,958 single CD34(+) cells from six human leukocyte antigen-matched sibling donor and recipient pairs, individual CD34(+) clones were recognized based on the observed donor- or recipient-specific mtDNA sequence somatic alteration. There was no overall reduction of mtDNA heterogeneity among CD34(+) cells from the recipient after transplantation. Samples collected from two donors over time showed the persistence of certain CD34(+) clones marked by specific mutations. Our results demonstrate the feasibility of distinguishing donor and recipient individual CD34(+) clones based on mtDNA mutations during engraftment. HSCs were not limited in number, and similar mtDNA heterogeneity levels suggested representation of the total stem cell compartment during rapid hematopoietic reconstitution in the recipient. Disclosure of potential conflicts of interest is found at the end of this article.
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, NIH, Building 10 CRC, Room 3E-5140, 10 Center Drive, Bethesda, Maryland 20892-1202, USA. yaoy3@nhlbi.nih.gov
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Yao
authors.forename: Richard W
authors.initials: RW
authors.lastname: Childs
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kajigaya
authors.forename: J Philip
authors.initials: JP
authors.lastname: McCoy
authors.forename: Neal S
authors.initials: NS
authors.lastname: Young
mesh_terms: D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D019070:Cell Lineage; D002469:Cell Separation / Q000379:methods; D002999:Clone Cells / Q000737:chemistry / Q000166:cytology; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000737:chemistry* / Q000166:cytology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000601:surgery; D035781:Siblings; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous
chemical_list: D018952:Antigens, CD34; D004272:DNA, Mitochondrial