1.干细胞维持基因组稳定性的特征和分子调控研究
干细胞是机体发育和组织稳态维持的基础,其遗传物质的稳定性维持对于正常发育及组织器官的稳态维持至关重要。由于功能特殊,干细胞在遗传物质稳定性调控上有其独特的特征和机制。我们以胚胎干细胞和神经干细胞为对象,研究干细胞调控DNA损伤反应(DNA damage response)和DNA复制压力反应(replication stress response)的特殊分子机制。这些研究将有助于推动干细胞的安全应用,并有助于理解相关发育异常和疾病的致病机理。
2.生殖干细胞的基础和应用研究
雌性生殖细胞的再生研究:哺乳动物雌性配子的发生是否存在再生机制一直是生殖生物学领域长期争议的话题,目前尚没有确凿的证据支持生理状况下存在卵巢生殖干细胞及其再生功能。我们以小鼠为模型,通过遗传手段着重研究生理状态下是否存在卵巢生殖干细胞及其再生活动,并在此基础上研究卵巢生殖干细胞的生物学特性和再生活动调控。
雄性生殖干细胞研究:树鼩(类灵长类动物)和猕猴(非人灵长类)与人的亲缘关系接近。我们重点研究树鼩和猕猴的精原干细胞的分子特征和体外长期扩增培养体系,并利用精原干细胞系进行基因修饰,创建疾病动物模型,模拟和研究人类疾病。
3.灵长类早期胚胎发育
由于伦理原因,人类自身的发育过程一直都非常不清楚,特别是早期胚胎的发育调控。利用云南的灵长类资源,我们开展了猕猴从卵细胞到着床前胚胎发育的系统研究,重点探讨最早期的细胞命运分化及发育多能性调控。
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4.Li CH, Yan LZ, Ban WZ, Tu Q, Wu Y, Wang L, Bi R, Ji S, Ma YH, Nie WH,Lv LB, Yao YG*, Zhao XD*,Zheng P*. Long-term propagation of tree shrew spermatogonial stem cells in culture and successful generation of transgenic offspring.Cell Research, 2017, 27(2):241-252.
5.Guo K#, Li CH#, Wang XY, He DJ,Zheng P*. Germ stem cells are active in postnatal mouse ovary under physiological conditions.Molecular Human Reproduction, 2016, 22(5): 316-328 (该工作受到杂志同期特邀评论,Mol Hum Reprod, 2016, 22:313-315).
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7.Zheng P*, Baibakov B, Wang XH, Dean J*. PtdIns(3,4,5)P3 is constitutively synthesized and required for spindle translocation during meiosis in mouse oocytes.Journal of Cell Science, 2013, 126(Pt 3):715-21.
8.Zheng P, Dean J*. Role of Filia, a maternal effect gene, in maintaining euploidy during cleavage stage mouse embryogenesis.Proc Natl Acad Sci USA, 2009, 106(18):7473-8.
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