A critical role for Apc in hematopoietic stem and progenitor cell survival.
A critical role for Apc in hematopoietic stem and progenitor cell survival.
复制标题
DOI：
10.1084/jem.20080578
复制
发表时间：
2008-09-01
期刊：
影响因子：
--
通讯作者：
Le Beau MM
中科院分区：
文献类型：
--
作者：
Qian Z;Chen L;Fernald AA;Williams BO;Le Beau MM
大肠腺瘤性息肉病（APC）肿瘤抑制因子通过调节Wnt信号级联反应参与结直肠癌的发生和发展。此外，Apc在多种细胞功能中发挥重要作用，包括细胞迁移和粘附、纺锤体组装和染色体分离。然而，它在成人造血过程中的作用尚不清楚。我们发现，Apc在体内的条件失活显着增加细胞凋亡和增强造血干细胞（HSC）/造血祖细胞（HPC）的细胞周期进入，导致其快速消失和骨髓衰竭。Apc消融引起的HSC/HPC缺陷是细胞自主的。此外，我们发现Apc的缺失导致髓系祖细胞池（普通髓系祖细胞、粒细胞-单核细胞祖细胞和巨核细胞-红系祖细胞）以及淋巴启动的多能祖细胞池的耗尽。编码Cdkn 1a、Cdkn 1b和Mcl 1的基因在候选HSC群体中急性Apc切除后发生下调。总之，我们的数据表明，Apc对于HSC和HPC的维持和存活至关重要。
The adenomatous polyposis coli (Apc) tumor suppressor is involved in the initiation and progression of colorectal cancer via regulation of the Wnt signaling cascade. In addition, Apc plays an important role in multiple cellular functions, including cell migration and adhesion, spindle assembly, and chromosome segregation. However, its role during adult hematopoiesis is unknown. We show that conditional inactivation of Apc in vivo dramatically increases apoptosis and enhances cell cycle entry of hematopoietic stem cells (HSCs)/ hematopoietic progenitor cells (HPCs), leading to their rapid disappearance and bone marrow failure. The defect in HSCs/HPCs caused by Apc ablation is cell autonomous. In addition, we found that loss of Apc leads to exhaustion of the myeloid progenitor pool (common myeloid progenitor, granulocyte-monocyte progenitor, and megakaryocyte-erythroid progenitor), as well as the lymphoid-primed multipotent progenitor pool. Down-regulation of the genes encoding Cdkn1a, Cdkn1b, and Mcl1 occurs after acute Apc excision in candidate HSC populations. Together, our data demonstrate that Apc is essential for HSC and HPC maintenance and survival.
登录
查看更多内容
影响因子：
11.4
作者：
BAEG, GH;MATSUMINE, A;AKIYAMA, T
通讯作者：
AKIYAMA, T
影响因子：
64.8
作者：
Hock, H;Hamblen, MJ;Orkin, SH
通讯作者：
Orkin, SH
影响因子：
64.5
作者：
Adolfsson, J;Månsson, R;Jacobsen, SEW
通讯作者：
Jacobsen, SEW
DOI：
10.1084/jem.20062395
发表时间：
2007-07-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Leung CG;Xu Y;Mularski B;Liu H;Gurbuxani S;Crispino JD
通讯作者：
Crispino JD
影响因子：
56.9
作者：
Cheng, T;Rodrigues, N;Scadden, DT
通讯作者：
Scadden, DT