A mutant allele of the Swi/Snf member BAF250a determines the pool size of fetal liver hemopoietic stem cell populations
A mutant allele of the Swi/Snf member BAF250a determines the pool size of fetal liver hemopoietic stem cell populations
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DOI：
10.1182/blood-2010-03-273862
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发表时间：
2010-09-09
期刊：
影响因子：
20.3
通讯作者：
Sauvageau, Guy
中科院分区：
文献类型：
--
作者：
Krosl, Jana;Mamo, Aline;Sauvageau, Guy
据信，造血干细胞（HSC）迅速定殖于胎肝（FL），扩增以建立足以维持整个生命的造血的HSC供应。因此，FL HSC与其主要静止的骨髓对应物相反，正在积极地循环，这表明FL微环境提供了支持HSC增殖和自我更新的独特信号。我们现在报告的产生和表征的突变等位基因Baf 250 a缺乏外显子2和3的小鼠。Baf 250 a（E2 E3/E2 E3）小鼠可存活至E19.5，但不能存活至出生后。最有趣的是，FL HSC数量在这些小鼠中明显高于对照同窝出生的小鼠，因此提高了Baf 250 a决定体内HSC池大小的可能性。有限稀释实验表明Baf 250 a（E2 E3/E2 E3）HSC的活性与野生型相当。相反，Baf 250 a（E2 E3/E2 E3）FL衍生的基质表现出上级发育匹配对照的造血支持潜力。据我们所知，这是第一次证明以细胞非自主方式运作的机制可以扩大胎儿HSC群体的池大小。（血。2010; 116（10）：1678-1684）
It is believed that hemopoietic stem cells (HSC), which colonize the fetal liver (FL) rapidly, expand to establish a supply of HSCs adequate for maintenance of hemopoiesis throughout life. Accordingly, FL HSCs are actively cycling as opposed to their predominantly quiescent bone marrow counterparts, suggesting that the FL microenvironment provides unique signals that support HSC proliferation and self-renewal. We now report the generation and characterization of mice with a mutant allele of Baf250a lacking exons 2 and 3. Baf250a(E2E3/E2E3) mice are viable until E19.5, but do not survive beyond birth. Most interestingly, FL HSC numbers are markedly higher in these mice than in control littermates, thus raising the possibility that Baf250a determines the HSC pool size in vivo. Limit dilution experiments indicate that the activity of Baf250a(E2E3/E2E3) HSC is equivalent to that of the wild-type counterparts. The Baf250a(E2E3/E2E3) FL-derived stroma, in contrast, exhibits a hemopoiesis-supporting potential superior to the developmentally matched controls. To our knowledge, this demonstration is the first that a mechanism operating in a cell nonautonomous manner canexpand the pool size of the fetal HSC populations. (Blood. 2010; 116(10):1678-1684)