In vitro self-renewal division of hematopoietic stem cells.
In vitro self-renewal division of hematopoietic stem cells.
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DOI：
10.1084/jem.192.9.1281
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发表时间：
2000-11-06
影响因子：
15.3
通讯作者：
Nakauchi, H
中科院分区：
文献类型：
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作者：
Ema, H;Takano, H;Sudo, K;Nakauchi, H
我们对造血干细胞（hsc）如何自我更新知之甚少。我们研究了造血干细胞在培养中的再生。在无血清的单细胞培养中，研究了不同细胞因子对CD34−/低c-Kit+Sca-1+谱系标记阴性（CD34−KSL）小鼠骨髓细胞分裂的影响。然后，我们对分裂的细胞进行了竞争性再生实验，以了解这种细胞分裂是否涉及造血干细胞的自我更新。在干细胞因子（SCF）存在的情况下，血小板生成素（TPO）比白细胞介素(IL)-3或IL-6更有效地诱导CD34−KSL细胞的首次细胞分裂。在TPO和SCF培养的单细胞中，有很大比例的细胞被检测到多系再生细胞，尽管这种培养条件导致HSC数量大幅减少。这些再生的细胞可以进一步移植到继发受体中。当成对的子细胞被单独研究时，一对中的一个产生了具有自我更新潜力的再生细胞，这表明不对称的自我更新分裂。本研究提供了一个HSC在培养中至少再生一个HSC的证据。
Little is known about how hematopoietic stem cells (HSCs) self-renew. We studied the regeneration of HSCs in culture. Effects of various cytokines on cell division of CD34−/low c-Kit+Sca-1+ lineage marker–negative (CD34−KSL) bone marrow cells of the mouse were first evaluated in serum-free single cell culture. We then performed a competitive repopulation assay on divided cells to ask if such cell division involved self-renewal of HSCs. In the presence of stem cell factor (SCF), thrombopoietin (TPO) induced a first cell division of CD34−KSL cells more efficiently than did interleukin (IL)-3 or IL-6. Multilineage repopulating cells were detected in a significant proportion of cells derived from single cells in culture with TPO and SCF, although this culture condition led to a substantial decrease in HSC number. These regenerated repopulating cells could be further transplanted into secondary recipients. When paired daughter cells were separately studied, one of a pair gave rise to repopulating cells with self-renewal potential, suggesting asymmetric self-renewal division. This study provides evidence that one HSC regenerates at least one HSC in culture.