Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Virchowstraße 179, 45147 Essen, Germany; German Cancer Consortium (DKTK).
Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Virchowstraße 179, 45147 Essen, Germany.
Stem Cell Reports. 2014 Dec 9;3(6):1058-72. doi: 10.1016/j.stemcr.2014.09.016. Epub 2014 Oct 23.
Hematopoietic stem and progenitor cells (HSPCs) can self-renew and create committed progenitors, a process supposed to involve asymmetric cell divisions (ACDs). Previously, we had linked the kinetics of CD133 expression with ACDs but failed to detect asymmetric segregation of classical CD133 epitopes on fixed, mitotic HSPCs. Now, by using a novel anti-CD133 antibody (HC7), we confirmed the occurrence of asymmetric CD133 segregation on paraformaldehyde-fixed and living HSPCs. After showing that HC7 binding does not recognizably affect biological features of human HSPCs, we studied ACDs in different HSPC subtypes and determined the developmental potential of arising daughter cells at the single-cell level. Approximately 70% of the HSPCs of the multipotent progenitor (MPP) fraction studied performed ACDs, and about 25% generated lymphoid-primed multipotent progenitor (LMPP) as wells as erythromyeloid progenitor (EMP) daughter cells. Since MPPs hardly created daughter cells maintaining MPP characteristics, our data suggest that under conventional culture conditions, ACDs are lineage instructive rather than self-renewing.
造血干细胞和祖细胞（HSPCs）可以自我更新并产生定向祖细胞，这个过程应该涉及不对称细胞分裂（ACDs）。之前，我们已经将 CD133 表达的动力学与 ACDs 联系起来，但未能在固定的有丝分裂 HSPCs 上检测到经典 CD133 表位的不对称分离。现在，通过使用一种新型抗 CD133 抗体（HC7），我们证实了在多聚甲醛固定和活 HSPCs 上发生不对称 CD133 分离。在表明 HC7 结合不会明显影响人 HSPCs 的生物学特征之后，我们研究了不同 HSPC 亚型中的 ACDs，并在单细胞水平上确定了出现的子细胞的发育潜力。在所研究的多能祖细胞（MPP）部分中，大约 70%的 HSPCs 进行了 ACDs，大约 25%产生了淋巴样前多能祖细胞（LMPP）和红系-髓系祖细胞（EMP）子细胞。由于 MPPs 几乎不会产生维持 MPP 特征的子细胞，我们的数据表明，在常规培养条件下，ACD 是谱系指导而不是自我更新的。
