期刊
LEUKEMIA
卷 28, 期 6, 页码 1308-1315出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/leu.2013.326
关键词
CD133; hematopoietic stem cell; CD34 negative; SCID-repopulating cell; IBMI; cord blood
资金
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan [21591251, 24591432]
- Science Frontier Program of the MEXT
- Strategic Research Base Development Program for Private Universities from the MEXT
- MEXT-Supported Program for the Strategic Research Foundation at Private Universities
- Promotion and Mutual Aid Corporation for Private Schools of Japan
- Japan Leukemia Research Foundation
- Mitsubishi Pharma Research Foundation
- Takeda Science Foundation
- Terumo Life Science Foundation
- SENSHIN Medical Research Foundation
- Grants-in-Aid for Scientific Research [22610013, 24591432, 21591251] Funding Source: KAKEN
The identification of human CD34(-) negative (CD34(-)) hematopoietic stem cells (HSCs) provides a new concept for the hierarchy in the human HSC compartment. Previous studies demonstrated that CD34(-) severe combined immunodeficiency (SCID)-repopulating cells (SRCs) are a distinct class of primitive HSCs in comparison to the well-characterized CD34(-) CD38(-) SRCs. However, the purification level of rare CD34(-) SRCs in 18 lineage marker-negative (Lin(-)) CD34(-) cells (1/1000) is still very low compared with that of CD34(+) CD38(-) SRCs (1/40). As in the mouse, it will be necessary to identify useful positive markers for a high degree of purification of rare human CD34(-)SRCs. Using 18Lin(-) CD34(-) cells, we analyzed the expression of candidate positive markers by flow cytometric analysis. We finally identified CD133 as a reliable positive marker of human CB-derived CD34(-) SRCs and succeeded in highly purifying primitive human CD34(-) HSCs. The limiting dilution analysis demonstrated that the incidence of CD34(-) SRCs in 18Lin(-) CD34(-) CD133(+) cells was 1/142, which is the highest level of purification of these unique CD34(-) SCs to date. Furthermore, CD133 expression clearly segregated the SRC activities of 18Lin(-) CD34(-) cells, as well as 18Lin(-) CD34(+) cells, in their positive fractions, indicating its functional significance as a common cell surface maker to isolate effectively both CD34(+) and CD34(-) SRCs.
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