Bmi1 Regulates Wnt Signaling in Hematopoietic Stem and Progenitor Cells.
Bmi1 Regulates Wnt Signaling in Hematopoietic Stem and Progenitor Cells.
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DOI：
10.1007/s12015-021-10253-4
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发表时间：
2021-12
影响因子：
4.8
通讯作者：
Liu, Yan
中科院分区：
文献类型：
--
作者：
Yu, Hao;Gao, Rui;Chen, Sisi;Liu, Xicheng;Wang, Qiang;Cai, Wenjie;Vemula, Sasidhar;Fahey, Aidan C.;Henley, Danielle;Kobayashi, Michihiro;Liu, Stephen Z.;Qian, Zhijian;Kapur, Reuben;Broxmeyer, Hal E.;Gao, Zhonghua;Xi, Rongwen;Liu, Yan
多梳蛋白Bmi1是造血干细胞(HSC)自我更新和终末分化所必需的。然而，它在造血干和祖细胞中的靶基因在很大程度上是未知的。我们进行了基因表达谱分析，发现Wnt信号通路的基因在Bmi1缺失的造血干细胞和祖细胞(HSPC)中显著升高。在造血细胞中，BMI1与Wnt信号通路的几个基因相关。此外，我们还发现Bmi1抑制了HSPC中Wnt基因的表达。重要的是，β-连环蛋白的丢失，减少了Wnt的激活，部分挽救了在Bmi1基因缺失小鼠中看到的造血干细胞自我更新和分化缺陷。因此，我们确定Bmi1是HSPC中Wnt信号通路的一个新的调节因子。鉴于Wnt信号通路在造血中起重要作用，我们的研究提示，调节Wnt信号通路可能具有促进HSC自我更新的潜力，从而改善HSC移植的结果。
Polycomb group protein Bmi1 is essential for hematopoietic stem cell (HSC) self-renewal and terminal differentiation. However, its target genes in hematopoietic stem and progenitor cells are largely unknown. We performed gene expression profiling assays and found that genes of the Wnt signaling pathway are significantly elevated in Bmi1 null hematopoietic stem and progenitor cells (HSPCs). Bmi1 is associated with several genes of the Wnt signaling pathway in hematopoietic cells. Further, we found that Bmi1 represses Wnt gene expression in HSPCs. Importantly, loss of β-catenin, which reduces Wnt activation, partially rescues the HSC self-renewal and differentiation defects seen in the Bmi1 null mice. Thus, we have identified Bmi1 as a novel regulator of Wnt signaling pathway in HSPCs. Given that Wnt signaling pathway plays an important role in hematopoiesis, our studies suggest that modulating Wnt signaling may hold potential for enhancing HSC self-renewal, thereby improving the outcomes of HSC transplantation.
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影响因子：
7.3
作者：
Liu Y;Liu F;Yu H;Zhao X;Sashida G;Deblasio A;Harr M;She QB;Chen Z;Lin HK;Di Giandomenico S;Elf SE;Yang Y;Miyata Y;Huang G;Menendez S;Mellinghoff IK;Rosen N;Pandolfi PP;Hedvat CV;Nimer SD
通讯作者：
Nimer SD
影响因子：
23.9
作者：
Liu Y;Elf SE;Miyata Y;Sashida G;Liu Y;Huang G;Di Giandomenico S;Lee JM;Deblasio A;Menendez S;Antipin J;Reva B;Koff A;Nimer SD
通讯作者：
Nimer SD
影响因子：
64.8
作者：
Reya, T;Duncan, AW;Weissman, IL
通讯作者：
Weissman, IL
DOI：
10.1084/jem.20080578
发表时间：
2008-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Qian Z;Chen L;Fernald AA;Williams BO;Le Beau MM
通讯作者：
Le Beau MM
影响因子：
4.8
作者：
Cho, Joon-Ho;Dimri, Manjari;Dimri, Goberdhan P.
通讯作者：
Dimri, Goberdhan P.