Sustained PU.1 levels balance cell-cycle regulators to prevent exhaustion of adult hematopoietic stem cells.
Sustained PU.1 levels balance cell-cycle regulators to prevent exhaustion of adult hematopoietic stem cells.
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DOI：
10.1016/j.molcel.2013.01.007
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发表时间：
2013-03-07
期刊：
影响因子：
16
通讯作者：
Tenen, Daniel G.
中科院分区：
文献类型：
--
作者：
Staber, Philipp B.;Zhang, Pu;Ye, Min;Welner, Robert S.;Nombela-Arrieta, Cesar;Bach, Christian;Kerenyi, Marc;Bartholdy, Boris A.;Zhang, Hong;Alberich-Jorda, Meritxell;Lee, Sanghoon;Yang, Henry;Ng, Felicia;Zhang, Junyan;Leddin, Mathias;Silberstein, Leslie E.;Hoefler, Gerald;Orkin, Stuart H.;Goettgens, Berthold;Rosenbauer, Frank;Huang, Gang;Tenen, Daniel G.
To provide a lifelong supply of blood cells, hematopoietic stem cells (HSCs) need to carefully balance both self-renewing cell divisions and quiescence. Although several regulators that control this mechanism have been identified, we demonstrate that the transcription factor PU.1 acts upstream of these regulators. So far, attempts to uncover PU.1’s role in HSC biology have failed because of the technical limitations of complete loss-of-function models. With the use of hypomorphic mice with decreased PU.1 levels specifically in phenotypic HSCs, we found reduced HSC long-term repopulation potential that could be rescued completely by restoring PU.1 levels. PU.1 prevented excessive HSC division and exhaustion by controlling the transcription of multiple cell-cycle regulators. Levels of PU.1 were sustained through autoregulatory PU.1 binding to an upstream enhancer that formed an active looped chromosome architecture in HSCs. These results establish that PU.1 mediates chromosome looping and functions as a master regulator of HSC proliferation.
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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
DOI：
10.1084/jem.20050075
发表时间：
2005-05-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dakic A;Metcalf D;Di Rago L;Mifsud S;Wu L;Nutt SL
通讯作者：
Nutt SL
影响因子：
64.5
作者：
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
Morrison, SJ
影响因子：
64.8
作者：
Hock, H;Hamblen, MJ;Orkin, SH
通讯作者：
Orkin, SH
影响因子：
11.4
作者：
Levantini, Elena;Lee, Sanghoon;Tenen, Daniel G.
通讯作者：
Tenen, Daniel G.