Asymmetric cell division within the human hernatopoietic stem and progenitor cell compartment: identification of asymmetrically segregating proteins
Asymmetric cell division within the human hernatopoietic stem and progenitor cell compartment: identification of asymmetrically segregating proteins
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DOI：
10.1182/blood-2006-11-055921
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发表时间：
2007-06-15
期刊：
影响因子：
20.3
通讯作者：
Giebel, Bernd
中科院分区：
文献类型：
--
作者：
Beckmann, Julia;Scheitza, Sebastian;Giebel, Bernd
许多原始人类造血细胞产生具有不同细胞命运和/或表现出不同增殖动力学的子细胞的研究结果表明，混血干细胞（HSC）和混血祖细胞（HPC）可以不对称分裂。然而，由于目前原始造血细胞室内不存在不对称分离的标记分子，因此缺乏明确的实验证明。因此，HSC/HPC 是否具有不对称分裂的能力，或者观察到的差异是否是由作用于有丝分裂后祖细胞的外在机制建立的，仍然是一个悬而未决的问题。在这里，我们鉴定了 4 种蛋白质（CD53、CD62L/L-选择素、CD63/lamp-3 和 CD71/转铁蛋白受体），它们在无基质培养物中分裂的约 20% 原始人类造血细胞中存在差异分离。因此，这首次表明HSC/HPC具有不对称分裂的能力。值得注意的是，这些蛋白质与替代干细胞标记 CD1 33 结合，有助于区分更原始的人类培养的 HSC/HPC。由于这些蛋白质中的 3 种，即转铁蛋白受体以及四跨膜蛋白 CD53 和 CD63，是内体相关蛋白，因此它们可能提供内体区室与 HSC/HPC 区室内不对称细胞分裂过程之间的联系。
The findings that many primitive human hematopoietic cells give rise to daughter cells that adopt different cell fates and/or show different proliferation kinetics suggest that hernatopoletic stem cells (HSCs) and hernatopoletic progenitor cells (HPCs) can divide asymmetrically. However, definitive experimental demonstration is lacking due to the current absence of asymmetrically segregating marker molecules within the primitive hematopoietic cell compartment. Thus, it remains an open question as to whether HSCs/HPCs have the capability to divide asymmetrically, or whether the differences that have been observed are established by extrinsic mechanisms that act on postmitotic progenitors. Here, we have identified 4 proteins (CD53, CD62L/L-selectin, CD63/ lamp-3, and CD71/transferrin receptor) that segregate differentially in about 20% of primitive human hernatopoietic cells that divide in stroma-free cultures. Therefore, this indicates for the first time that HSCs/HPCs have the capability to divide asymmetrically. Remarkably, these pro- teins, in combination with the surrogate stem-cell marker CD1 33, help to discriminate the more primitive human cultivated HSCs/HPCs. Since 3 of these proteins, the transferrin receptor and the tetraspanins CD53 and CD63, are endosomalassociated proteins, they may provide a link between the endosomal compartment and the process of asymmetric cell division within the HSC/HPC compartment.