کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10904185 | 1086564 | 2013 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Transgenic expression of BRCA1 disturbs hematopoietic stem and progenitor cells quiescence and function
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کلمات کلیدی
HSCFACSMEPGMPHSCsCLPsCommon lymphoid progenitorsCMPscommon myeloid progenitorsmultipotent progenitorsbreast cancer type 1 susceptibility protein - سرطان پستان نوع 1 حساسیت پروتئینfluorescence activated cell sorter - فلورسانس سلول فعال شده سلولbone marrow - مغز استخوانCell cycle - چرخه سلولیBRCA1 - ژن BRCA1
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The balance between quiescence and proliferation of HSCs is an important regulator of hematopoiesis. Loss of quiescence frequently results in HSCs exhaustion, which underscores the importance of tight regulation of proliferation in these cells. Studies have indicated that cyclin-dependent kinases are involved in the regulation of quiescence in HSCs. BRCA1 plays an important role in the repair of DNA double-stranded breaks, cell cycle, apoptosis and transcription. BRCA1 is expressed in the bone marrow. However, the function of BRCA1 in HSCs is unknown. In our study, we generated BRCA1 transgenic mice to investigate the effects of BRCA1 on the mechanisms of quiescence and differentiation in HSCs. The results demonstrate that over-expression of BRCA1 in the bone marrow impairs the development of B lymphocytes. Furthermore, BRCA1 induced an increase in the number of LSKs, LT-HSCs, ST-HSCs and MPPs. A competitive transplantation assay found that BRCA1 transgenic mice failed to reconstitute hematopoiesis. Moreover, BRCA1 regulates the expression of p21waf1/cip1 and p57kip2, which results in a loss of quiescence in LSKs. Together, over-expression of BRCA1 in bone marrow disrupted the quiescent of LSKs, induced excessive accumulation of LSKs, and disrupted differentiation of the HSCs, which acts through the down-regulated of p21waf1/cip1 and p57kip2.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 319, Issue 17, 15 October 2013, Pages 2739-2746
Journal: Experimental Cell Research - Volume 319, Issue 17, 15 October 2013, Pages 2739-2746
نویسندگان
Lin Bai, Guiying Shi, Xu Zhang, Wei Dong, Lianfeng Zhang,