Molecular signatures of quiescent, mobilized and leukemia-initiating hematopoietic stem cells.
Molecular signatures of quiescent, mobilized and leukemia-initiating hematopoietic stem cells.
复制标题
DOI：
10.1371/journal.pone.0008785
复制
发表时间：
2010-01-20
期刊：
影响因子：
3.7
通讯作者：
Weissman IL
中科院分区：
文献类型：
--
作者：
Forsberg EC;Passegué E;Prohaska SS;Wagers AJ;Koeva M;Stuart JM;Weissman IL
造血干细胞（HSC）是一种罕见的多能细胞，能够产生血液系统的所有特化细胞。HSC静止的适当调节被认为是维持其终身功能的关键;然而，控制干细胞静止的分子途径仍然缺乏表征。同样，驱动白血病发生的分子事件仍然难以捉摸。在这项研究中，我们比较了稳态骨髓造血干细胞的基因表达谱的非自我更新的多能祖细胞;动员药物，扩大造血干细胞池和诱导出口的骨髓造血干细胞治疗;和白血病造血干细胞在慢性髓细胞性白血病小鼠模型。通过交叉得到的差异调节基因的列表，我们确定了一个子集的分子，下调在所有三种情况下，因此可能是特别重要的正常，静止HSC的维护和功能。这些结果确定了HSC的潜在关键调节因子，并深入了解了HSC动员用于移植和从癌症干细胞发展成白血病的临床重要过程。
Hematopoietic stem cells (HSC) are rare, multipotent cells capable of generating all specialized cells of the blood system. Appropriate regulation of HSC quiescence is thought to be crucial to maintain their lifelong function; however, the molecular pathways controlling stem cell quiescence remain poorly characterized. Likewise, the molecular events driving leukemogenesis remain elusive. In this study, we compare the gene expression profiles of steady-state bone marrow HSC to non-self-renewing multipotent progenitors; to HSC treated with mobilizing drugs that expand the HSC pool and induce egress from the marrow; and to leukemic HSC in a mouse model of chronic myelogenous leukemia. By intersecting the resulting lists of differentially regulated genes we identify a subset of molecules that are downregulated in all three circumstances, and thus may be particularly important for the maintenance and function of normal, quiescent HSC. These results identify potential key regulators of HSC and give insights into the clinically important processes of HSC mobilization for transplantation and leukemic development from cancer stem cells.
登录
查看更多内容
影响因子：
64.5
作者：
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
Morrison, SJ
影响因子：
2.6
作者：
Antonchuk, J;Sauvageau, G;Humphries, RK
通讯作者：
Humphries, RK
影响因子：
158.5
作者：
Jamieson, CHM;Ailles, LE;Weissman, IL
通讯作者：
Weissman, IL
影响因子：
2.1
作者：
Dick, JE;Lapidot, T
通讯作者：
Lapidot, T
DOI：
10.1073/pnas.2637010100
发表时间：
2004-01-06
影响因子：
11.1
作者：
Cao, YA;Wagers, AJ;Contag, CH
通讯作者：
Contag, CH