کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9954140 1539359 2018 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The influence of retinoic acid-induced differentiation on the radiation response of male germline stem cells
ترجمه فارسی عنوان
تأثیر تمایز ناشی از اسید رتینوئیک بر پاسخ واکنش سلول های بنیادی جنینی مردانه
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
چکیده انگلیسی
Lifelong mammalian male fertility is maintained through an intricate balance between spermatogonial proliferation and differentiation. DNA damage in spermatogonia, for instance caused by chemo- or radiotherapy, can induce cell cycle arrest or germ cell apoptosis, possibly resulting in male infertility. Spermatogonia are generally more radiosensitive and prone to undergo apoptosis than somatic cells. Among spermatogonial subtypes the response to DNA damage is differentially modulated; undifferentiated spermatogonia, including the spermatogonial stem cells (SSCs), are relatively radio-resistant, whereas differentiating spermatogonia are very radiosensitive. To investigate the molecular mechanisms underlying this difference, we used an in vitro system consisting of mouse male germline stem (GS) cells that can be induced to differentiate. Using RNA-sequencing analysis, we analyzed the response of undifferentiated and differentiating GS cells to ionizing radiation (IR). At the RNA expression level, both undifferentiated and differentiating GS cells showed a very similar response to IR. Protein localization of several genes found to be involved in either spermatogonial differentiation or radiation response was investigated using mouse testis sections. For instance, we found that the transcription factor PDX1 was specifically expressed in undifferentiated spermatogonia and thus may be a novel marker for these cells. Interestingly, also at the protein level, undifferentiated GS cells showed a more pronounced upregulation of p53 in response to IR than differentiating GS cells. The higher p53 protein level in undifferentiated spermatogonia may preferentially induce cell cycle arrest, thereby giving these cells more time to repair inflicted DNA damage and increase their radio-resistance.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: DNA Repair - Volume 70, October 2018, Pages 55-66
نویسندگان
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