Lin-4、miR-125a调控涡虫chromatoid body对干细胞增殖与分化的影响及机制研究
结题报告
批准号:
U1504307
项目类别:
联合基金项目
资助金额:
27.0 万元
负责人:
张一折
依托单位:
学科分类:
C0602.基因表达及非编码序列调控
结题年份:
2018
批准年份:
2015
项目状态:
已结题
项目参与者:
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中文摘要
涡虫因有强大再生能力和大量成体干细胞,成为理想的再生和干细胞研究模式生物,chromatoid-body是其干细胞显著特征,在增殖和分化中起重要作用,但机制不清。我们研究发现Lin-4、miR-125a调控chromatoid-body关键蛋白LSM14、DjCBC-1;文献报道miR-125能调控干细胞增殖和分化。我们推测Lin-4、miR-125a通过调控chromatoid-body而调控涡虫干细胞特性、影响再生。本研究拟通过原位杂交等研究Lin-4、miR-125a及靶在再生各时期、部位表达特征,验证调控关系;通过miRNA-mimics、miRNA-inhibitor等研究Lin-4、miR-125a对chromatoid-body的调控机制;初步阐明chromatoid-body在涡虫干细胞增殖及分化中的作用及机制,为以涡虫为模式生物的再生生物学及干细胞在体研究进行有益的探索。
英文摘要
Stem cells hold great potential for regenerative medicine, but there is still a lot of problems about culture difficulties and high risks. In order to overcome these problems, it is pivotal to obtain a clearer understanding of the molecular mechanisms that underlie every aspect of stem cell biology in vivo. Because these studies are relatively limited in mammalian, planarians represent a suitable model or dissecting relevant molecular details. Planarian, an ideal regeneration and stem cell research model organism, has strong regeneration ability and a large number of adult stem cells. It possesses extraordinary ability to regenerate lost body parts after amputation, pluripotent adult somatic stem cells, called neoblasts, assure this regenerative ability. Chromatoid body is its remarkable characteristics, and plays an important role in the self-renewal and differentiation, but the specific molecular mechanism is not clear. Our initial study found that Lin-4 and its homologous miR-125 chromatoid body control key protein LSM-14 and DjCBC-1; in the literatures miR-125 was reported to regulate the proliferation and differentiation of stem cells. We hypothesized that Lin-4, miR-125 can regulation planaria stem cell characteristics and differentiation to influence regeneration by the regulation of chromatoid body. This study proposed to investigate Lin-4, miR-125 and target in the regeneration each period, site expression features, verification regulation relationship, confirmed regulation function by in situ hybridization; using the miRNA mimics, miRNA inhibitor and RNAi to investigate control mechanism of chromatoid body by Lin-4 and miR-125; Preliminary clarify function and mechanism in the self-renewal and differentiation process of chromatoid body in planaria stem cell. We explore gene expression regulation mechanism of planaria chromatoid body stem cells self-renewal and differentiation process through miRNA-mRNA regulation relationship. Through the effect of Lin-4 and miR-125a on the regulation of stem cell proliferation and differentiation by chromatoid body of planarian and mechanism study, It will be a beneficial exploration for biological regenerative biology and research of stem cells in vivo using planarian as model. Meanwhile, It provides new ideas and useful information to the field of regenerative medicine and wound healing base on stem cells.
涡虫因有强大再生能力和大量成体干细胞,成为理想的再生和干细胞研究模式生物,chromatoid-body是其干细胞显著特征,在增殖和分化中起重要作用,但机制不清。我们研究发现了Lin-4、miR-125a调控chromatoid-body关键蛋白LSM14、DjCBC-1;文献报道miR-125能调控干细胞增殖和分化。本研究通过原位杂交等研究了Lin-4、miR-125a及靶在再生各时期、部位表达特征,验证调控关系;通过miRNA-mimics、miRNA-inhibitor等研究了Lin-4、miR-125a对chromatoid-body的调控机制;初步阐明了chromatoid-body在涡虫干细胞增殖及分化中的作用及机制。. 本研究完成了再生相关microRNA的功能筛选,预测了涡虫体内microRNA的再生调控网络,并对其中Lin-4、miR-125a的调控机制进行了进一步研究,初步阐明了Lin-4对chromatoid body的调控机制,并从microRNA再生网络中选取了TGF-β信号通路下游基因TINP1,进一步探讨了TINP1在涡虫中的再生调控功能,为以涡虫为模式生物的再生生物学及干细胞在体研究进行了有益的探索。
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
DOI:10.1016/j.ijbiomac.2019.01.014
发表时间:2019
期刊:International Journal of Biological Macromolecules
影响因子:8.2
作者:Tian Qingnan;Zhao Guixia;Sun Yujia;Yuan D;an;Guo Qi;Zhang Yizhe;Liu Jiaqian;Zhang Shoutao
通讯作者:Zhang Shoutao
DOI:10.1016/j.bbrc.2017.09.032
发表时间:2017-11-25
期刊:BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
影响因子:3.1
作者:Guo, Qi;Zhao, Guixia;Zhang, Shoutao
通讯作者:Zhang, Shoutao
国内基金
海外基金