c-Kit-mediated functional positioning of stem cells to their niches is essential for maintenance and regeneration of adult hematopoiesis.
c-Kit-mediated functional positioning of stem cells to their niches is essential for maintenance and regeneration of adult hematopoiesis.
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DOI：
10.1371/journal.pone.0026918
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Rafii S
中科院分区：
文献类型：
--
作者：
Kimura Y;Ding B;Imai N;Nolan DJ;Butler JM;Rafii S
造血干细胞和祖细胞（HSPCs）通过与其小生境相互作用维持和重建成体造血细胞的机制尚不清楚。为了在功能上和遗传上跟踪HSPCs及其小生境的定位，我们采用了新的突变loxPs，lox 66和lox 71以及Cre重组酶技术来有条件地删除成年小鼠中的c-Kit，同时使GFP在c-Kit缺陷细胞中表达。条件性删除c-Kit导致稳态和骨髓消融后的造血功能衰竭和脾萎缩，导致治疗的成年小鼠死亡。在骨髓内，将表达c-Kit的GFP+细胞定位于表达Kit配体（KL）的小生境细胞。这种c-Kit介导的细胞粘附对于HSPCs的长期维持和扩增至关重要。这些结果为在特定生态位内递送KL以维持和恢复造血奠定了基础。
The mechanism by which hematopoietic stem and progenitor cells (HSPCs) through interaction with their niches maintain and reconstitute adult hematopoietic cells is unknown. To functionally and genetically track localization of HSPCs with their niches, we employed novel mutant loxPs, lox66 and lox71 and Cre-recombinase technology to conditionally delete c-Kit in adult mice, while simultaneously enabling GFP expression in the c-Kit-deficient cells. Conditional deletion of c-Kit resulted in hematopoietic failure and splenic atrophy both at steady state and after marrow ablation leading to the demise of the treated adult mice. Within the marrow, the c-Kit-expressing GFP+ cells were positioned to Kit ligand (KL)-expressing niche cells. This c-Kit-mediated cellular adhesion was essential for long-term maintenance and expansion of HSPCs. These results lay the foundation for delivering KL within specific niches to maintain and restore hematopoiesis.
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影响因子：
23.9
作者：
Butler JM;Nolan DJ;Vertes EL;Varnum-Finney B;Kobayashi H;Hooper AT;Seandel M;Shido K;White IA;Kobayashi M;Witte L;May C;Shawber C;Kimura Y;Kitajewski J;Rosenwaks Z;Bernstein ID;Rafii S
通讯作者：
Rafii S
影响因子：
64.5
作者：
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
Morrison, SJ
影响因子：
14.9
作者：
Oberdoerffer, P;Otipoby, KL;Rajewsky, K
通讯作者：
Rajewsky, K
影响因子：
64.8
作者：
Mikkola, HKA;Klintman, J;Orkin, SH
通讯作者：
Orkin, SH
DOI：
10.1196/annals.1392.021
发表时间：
2007-01-01
期刊：
HEMATOPOIETIC STEM CELLS VI
影响因子：
--
作者：
Wilson, Anne;Oser, Gabriela M.;Trumpp, Andreas
通讯作者：
Trumpp, Andreas