Human cord blood-derived primitive progenitors are enriched in CD34+c-kit- cells: correlation between long-term culture-initiating cells and telomerase expression.
We studied the functional characteristics of subpopulations of cord blood-derived CD34+ cells expressing different levels of CD38 and c-kit antigens, using clonal cell culture and long-term culture with allogeneic bone marrow stromal cells or the MS-5 murine stromal cell line to assay long-term culture-initiating cells (LTC-IC) in each subpopulation. To investigate the capacity for replication, proliferation, and differentiation of each subpopulation of CD34+ cells, we also studied the correlation between LTC-IC and telomerase activity. After 5 weeks of coculture, LTC-IC accounted for one out of 32 CD34+CD38- cells and one out of 33 CD34+c-kit- cells. In contrast, the frequency of LTC-IC was low in their antigen-positive counterparts (one per 84 CD34+CD38+ cells, one per 90 CD34+c-kit(low) cells, and very low among CD34+c-kit(high) cells). It was noteworthy that some LTC-IC derived from CD34+CD38- as well as CD34+c-kit- cells generated colony-forming cells (CFCs) after up to 9 weeks of coculture. Telomerase activity was consistently low in CD34+CD38- and CD34+c-kit- cells compared to CD38+ or c-kit(high or low) cells, suggesting that CD34+CD38- or c-kit- cells are likely to be more quiescent. These results suggest that the CD34+CD38- and CD34+c-kit- cell populations are primitive stem/progenitor cells, and that the telomerase activity of these cells correlates with their proliferative capacity as well as their stage of differentiation.
Sakabe
H
H
Department of Hygiene, Kyoto Prefectural University of Medicine, Japan.
Yahata
N
N
Kimura
T
T
Zeng
Z Z
ZZ
Minamiguchi
H
H
Kaneko
H
H
Mori
K J
KJ
Ohyashiki
K
K
Ohyashiki
J H
JH
Toyama
K
K
Abe
T
T
Sonoda
Y
Y
D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis / Q000097:blood*; D000943:Antigens, Differentiation / Q000096:biosynthesis; D016466:CHO Cells / Q000378:metabolism; D002478:Cells, Cultured; D006224:Cricetinae; D005312:Fetal Blood / Q000166:cytology / Q000201:enzymology*; D005784:Gene Amplification; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000201:enzymology*; D006801:Humans; D016133:Polymerase Chain Reaction; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000097:blood*; D012680:Sensitivity and Specificity; D019098:Telomerase / Q000096:biosynthesis*; D016615:Telomere; D013997:Time Factors
D018952:Antigens, CD34; D000943:Antigens, Differentiation; D019009:Proto-Oncogene Proteins c-kit; D019098:Telomerase