Lu Min, Kawamoto Hiroshi, Katsube Yoshihiro, Ikawa Tomokatsu, Katsura Yoshimoto
Department of Immunology, Institute for Frontier Medical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
J Immunol. 2002 Oct 1;169(7):3519-25. doi: 10.4049/jimmunol.169.7.3519.
We have previously shown that the common progenitors for myeloid, T, and B cell lineages are enriched in the earliest population of murine fetal liver. However, it remained unclear whether such multipotent progenitors represent the pluripotent progenitors capable of generating all hemopoietic cells or they also comprise progenitors restricted to myeloid, T, and B cell lineages. To address this issue, we have developed a new clonal assay covering myeloid, erythroid, T, and B cell lineages, and using this assay the developmental potential of individual cells in subpopulations of lineage marker-negative (Lin(-)) c-kit(+) murine fetal liver cells was investigated. We identified the progenitor generating myeloid, T, and B cells, but not erythroid cells in the Sca-1(high) subpopulation of Lin(-)c-kit(+) cells that can thus be designated as the common myelolymphoid progenitor (CMLP). Common myeloerythroid progenitors were also detected. These findings strongly suggest that the first branching point in fetal hemopoiesis is between the CMLP and common myeloerythroid progenitors. T and B cell progenitors may be derived from the CMLP through the previously identified myeloid/T and myeloid/B bipotent stages, respectively.
我们之前已经表明,髓系、T细胞和B细胞谱系的共同祖细胞在小鼠胎肝的最早期细胞群中富集。然而,尚不清楚这种多能祖细胞是否代表能够产生所有造血细胞的多能祖细胞,或者它们是否还包含限于髓系、T细胞和B细胞谱系的祖细胞。为了解决这个问题,我们开发了一种涵盖髓系、红系、T细胞和B细胞谱系的新克隆分析方法,并使用该方法研究了谱系标记阴性(Lin(-))c-kit(+)小鼠胎肝细胞亚群中单个细胞的发育潜能。我们在Lin(-)c-kit(+)细胞的Sca-1(高)亚群中鉴定出了产生髓系、T细胞和B细胞,但不产生红系细胞的祖细胞,因此可将其指定为常见髓淋巴祖细胞(CMLP)。还检测到了常见的髓红系祖细胞。这些发现强烈表明,胎儿造血的第一个分支点位于CMLP和常见髓红系祖细胞之间。T细胞和B细胞祖细胞可能分别通过先前确定的髓系/T细胞和髓系/B细胞双能阶段从CMLP衍生而来。