Hematopoietic stem cells proliferate until after birth and show a reversible phase-specific engraftment defect
Hematopoietic stem cells proliferate until after birth and show a reversible phase-specific engraftment defect
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DOI：
10.1172/jci28310
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发表时间：
2006-10-01
影响因子：
15.9
通讯作者：
Eaves, Connie J.
中科院分区：
文献类型：
--
作者：
Bowie, Michelle B.;McKnight, Kristen D.;Eaves, Connie J.
造血干细胞增殖和骨髓植入的调控是一个重要但知之甚少的过程，特别是在个体发育过程中。在这里，我们发现在小鼠中，所有的HSC都在循环，直到出生后3周。然后，在一周内，大多数人变得安静。在4周龄之前，具有长期多谱系再生活性的增殖HSC在S/G（2）/M时显示植入缺陷。在这些细胞周期阶段，它们的CXC趋化因子配体12（CXCL 12;也称为基质细胞衍生因子1 [SDF-1]）表达短暂增加。当细胞在注射前进入G（1）或当宿主（而不是细胞）用CXCL 12拮抗剂预处理时，S/G2/M中HSC的移植活性缺陷被逆转。有趣的是，CXCL 12拮抗剂预处理的增强作用仅限于S/G2/M中长期多谱系再生HSC的移植。这些结果表明，我们认为这是一个新的HSC调控检查点在发展过程中。它们还表明HSC以随着细胞周期进展而改变的方式表达CXCL 12的能力，并且与可以通过体内施用CXCL 12拮抗剂克服的缺陷性植入相关。
The regulation of HSC proliferation and engraftment of the BM is an important but poorly understood process, particularly during ontogeny. Here we show that in mice, all HSCs are cycling until 3 weeks after birth. Then, within 1 week, most became quiescent. Prior to 4 weeks of age, the proliferating HSCs with long-term multilineage repopulating activity displayed an engraftment defect when transiting S/G(2)/M. During these cell cycle phases, their expression of CXC chemokine ligand 12 (CXCL12; also referred to as stromal cell-derived factor 1 [SDF-1]) transiently increased. The defective engrafting activity of HSCs in S/G2/M was reversed when cells were allowed to progress into G(1) prior to injection or when the hosts (but not the cells) were pretreated with a CXCL12 antagonist. Interestingly, the enhancing effect of CXCL12 antagonist pretreatment was exclusive to transplants of long-term multilineage repopulating HSCs in S/G2/M. These results demonstrate what we believe to be a new HSC regulatory checkpoint during development. They also suggest an ability of HSCs to express CXCL12 in a fashion that changes with cell cycle progression and is associated with a defective engraftment that can be overcome by in vivo administration of a CXCL12 antagonist.