Primitive human hematopoietic cells give rise to differentially specified daughter cells upon their initial cell division
Primitive human hematopoietic cells give rise to differentially specified daughter cells upon their initial cell division
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DOI：
10.1182/blood-2005-08-3139
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发表时间：
2006-03-01
期刊：
影响因子：
20.3
通讯作者：
Punzel, M
中科院分区：
文献类型：
--
作者：
Giebel, B;Zhang, T;Punzel, M
通常预测干细胞不对称分裂，产生维持干细胞能力的子细胞，和1个子细胞致力于分化。虽然不对称干细胞分裂已被证明发生在模式生物（如果蝇），它仍然是一个谜，原始造血细胞在哺乳动物中是否真的可以不对称分裂。在我们的实验中，我们挑战了这个问题，并在单细胞水平上分析了原始人类造血细胞分离后代的发育能力。我们首次发现，绝大多数最原始的、体外可检测的人类造血细胞产生了采用不同细胞命运的子细胞; 1继承了母细胞的发育能力，1变得更加特异。相比之下，研究中大约一半的定向祖细胞产生了子细胞，两者都采用了母亲的细胞命运。虽然我们的数据是兼容的不对称细胞分裂的模型，细胞命运规范的其他机制进行了讨论。此外，我们描述了一种新的人造血祖细胞，具有形成自然杀伤（NK）细胞以及巨噬细胞的能力，但不能形成其他髓系细胞。
It is often predicted that stem cells divide asymmetrically, creating a daughter cell that maintains the stem-cell capacity, and 1 daughter cell committed to differentiation. While asymmetric stem-cell divisions have been proven to occur in model organisms (eg, in Drosophila), it remains illusive whether primitive hematopoietic cells in mammals actually can divide asymmetrically. In our experiments we have challenged this question and analyzed the developmental capacity of separated offspring of primitive human hematopoietic cells at a single-cell level. We show for the first time that the vast majority of the most primitive, in vitro-detectable human hematopoietic cells give rise to daughter cells adopting different cell fates; 1 inheriting the developmental capacity of the mother cell, and 1 becoming more specified. In contrast, approximately half of the committed progenitor cells studied gave rise to daughter cells, both of which adopted the cell fate of their mother. Although our data are compatible with the model of asymmetric cell division, other mechanisms of cell fate specification are discussed. In addition, we describe a novel human hematopoietic progenitor cell that has the capacity to form natural killer (NK) cells as well as macrophages, but not cells of other myeloid lineages.