Polycomb group gene rae28 is required for sustaining activity of hematopoietic stem cells.
Polycomb group gene rae28 is required for sustaining activity of hematopoietic stem cells.
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polycomb基因rae28是维持造血干细胞活性所必需的。
DOI：
10.1084/jem.20011911
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发表时间：
2002-03-18
期刊：
影响因子：
--
通讯作者：
Takihara Y
中科院分区：
文献类型：
--
作者：
Ohta H;Sawada A;Kim JY;Tokimasa S;Nishiguchi S;Humphries RK;Hara J;Takihara Y
rae 28基因（rae 28），也称为mph 1，是果蝇多同源基因（Polycomb group genes，PcG）的一个成员。rae 28构成PcG复合物1，用于维持曾经启动的转录状态，推测是通过调节染色质结构。rae 28缺陷动物（rae 28 −/−）的胎肝造血活性受损，表现为胚胎发育期间多系造血祖细胞的进行性减少和脾中集落形成单位（CFU-S12）的扩增不良。体外长期培养起始细胞测定表明造血干细胞（HSC）减少，这在体内通过致死性辐照同种受体小鼠的重建实验得到证实。竞争性再生单位（CRU）反映了支持多系血细胞生产的HSC。生成了CRU，而rae 28 − / −胎肝中的CRU数量减少了20倍。我们还进行了系列移植实验，以半定量地测量体内CRU的自我更新活性。在rae 28 − / −中，CRU的自我更新活性降低了15倍。因此，受损的HSC被认为会降低rae 28 − / −胎肝中的造血活性。这是第一份报告表明rae 28在维持HSC的活性以维持造血方面具有关键作用。
The rae28 gene (rae28), also designated as mph1, is a mammalian ortholog of the Drosophila polyhomeotic gene, a member of Polycomb group genes (PcG). rae28 constitutes PcG complex 1 for maintaining transcriptional states which have been once initiated, presumably through modulation of the chromatin structure. Hematopoietic activity was impaired in the fetal liver of rae28-deficient animals (rae28 −/−), as demonstrated by progressive reduction of hematopoietic progenitors of multilineages and poor expansion of colony forming units in spleen (CFU-S12) during embryonic development. An in vitro long-term culture-initiating cell assay suggested a reduction in hematopoietic stem cells (HSCs), which was confirmed in vivo by reconstitution experiments in lethally irradiated congenic recipient mice. The competitive repopulating units (CRUs) reflect HSCs supporting multilineage blood-cell production. CRUs were generated, whereas the number of CRUs was reduced by a factor of 20 in the rae28 − / − fetal liver. We also performed serial transplantation experiments to semiquantitatively measure self-renewal activity of CRUs in vivo. Self-renewal activity of CRUs was 15-fold decreased in rae28 − / −. Thus the compromised HSCs were presumed to reduce hematopoietic activity in the rae28 − / − fetal liver. This is the first report to suggest that rae28 has a crucial role in sustaining the activity of HSCs to maintain hematopoiesis.
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作者：
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DOI：
10.1073/pnas.95.3.1195
发表时间：
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影响因子：
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