Deletion of the Imprinted Gene Grb10 Promotes Hematopoietic Stem Cell Self-Renewal and Regeneration.
Deletion of the Imprinted Gene Grb10 Promotes Hematopoietic Stem Cell Self-Renewal and Regeneration.
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DOI：
10.1016/j.celrep.2016.10.025
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发表时间：
2016-11-01
期刊：
影响因子：
8.8
通讯作者：
Chute JP
中科院分区：
文献类型：
--
作者：
Yan X;Himburg HA;Pohl K;Quarmyne M;Tran E;Zhang Y;Fang T;Kan J;Chao NJ;Zhao L;Doan PL;Chute JP
印迹基因是成体干细胞差异表达的基因，但其调控成体干细胞命运的功能尚不完全清楚。在这里，我们展示了生长因子受体结合蛋白10(Grb10)，一个印迹基因，调节造血干细胞(HSC)的自我更新和再生。与Grb10+/+小鼠相比，Grb10母体等位基因在小鼠(Grb10m/+小鼠)中的缺失显著增加了HSC的长期再繁殖能力。全身照射后，与Grb10+/+小鼠相比，Grb10 m/+小鼠表现出更快的HSC再生和造血重建。在竞争性移植或脑损伤后，Grb10缺陷的HSC表现出与CDK4和Cyclin E上调相称的增殖。此外，在Grb10缺陷的小鼠中观察到的增强的HSC再生依赖于Akt/mTORC1通路的激活。本研究揭示了印迹基因Grb10在调节HSC自我更新和再生中的作用，并提示抑制Grb10可以促进体内的造血再生。
Imprinted genes are differentially expressed by adult stem cells, but their functions in regulating adult stem cell fate are incompletely understood. Here, we show that growth factor receptor bound protein 10 (Grb10), an imprinted gene, regulates hematopoietic stem cell (HSC) self-renewal and regeneration. Deletion of the maternal allele of Grb10 in mice (Grb10 m/+ mice) substantially increased HSC long-term repopulating capacity compared to Grb10 +/+ mice. Following total body irradiation (TBI), Grb10 m/+ mice demonstrated accelerated HSC regeneration and hematopoietic reconstitution compared to Grb10 +/+ mice. Grb10-deficient HSCs displayed increased proliferation following competitive transplantation or TBI, commensurate with upregulation of CDK4 and Cyclin E. Furthermore, the enhanced HSC regeneration observed in Grb10 – deficient mice was dependent on activation of the Akt/mTORC1 pathway. This study reveals a function for the imprinted gene, Grb10, in regulating HSC self-renewal and regeneration and suggests that inhibition of Grb10 can promote hematopoietic regeneration in vivo.
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影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1073/pnas.1532175100
发表时间：
2003-07-08
影响因子：
11.1
作者：
Charalambous, M;Smith, FM;Ward, A
通讯作者：
Ward, A
影响因子：
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影响因子：
23.9
作者：
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通讯作者：
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影响因子：
7.7
作者：
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