中央研究所細胞與個體生物學
Stem Cell Research Lab
Research
研究方向
我們實驗室主要是利用果蠅卵巢的生殖幹細胞來研究幹細胞在受到外在環境的刺激時如何受到調控以維持組織的恆定。成體幹細胞對於組織恆定的維持十分重要。這是因為成體幹細胞以不對稱分裂的方式產生二個子細胞, 其中一個子細胞會取代原有的幹細胞,而另一個子細胞則會分裂及分化以補充組織所耗損的細胞。幹細胞的活性減低會造成組織衰退,而幹細胞的活性被不正常的活化時則會轉變成癌幹細胞進而導致腫瘤的生成。因此幹細胞的活性必須受到嚴格的調控。成體幹細胞位在一個特異化的微小環境,稱之為幹細胞 niche。Niche 細胞會釋放不同的蛋白訊息來調控幹細胞,例如BMP 訊息對於許多幹細胞的維持都十分重要。除此之外,在外界環境的刺激之下生物體也能自行協調幹細胞的活動以維持體內各個組織的恆定。然而截至目前為止對於外界刺激如何影響幹細胞的分子機制仍舊不清楚。
Research Interest 
My laboratory studies regulation of stem cells in response to diet and aging. Adult stem cells perform asymmetrical division to self-renew and to produce differentiating cells to replenish lost cells in tissues. Stem cells reside in a specialized environment, or niche, which provides tissue-intrinsic signals that regulate stem cell function. Stem cell behavior is also modulated by tissue-extrinsic factors that mediate the effects of changes of environmental and physiological status, for instance nutritional inputs and aging, respectively. We are interested in how stem cells adjust their division rates and lifespan to maintain tissue homeostasis in response to external environments and physiological status, and intend to investigate the mechanisms underlying this process using the fruit fly, Drosophila melanogster.
Drosophila Ovary is an excellent model system to study stem cell behavior
Drosophila ovarian GSCs are well characterized. One Drosophila female has a pair of ovaries, which are composed of strings of ovarioles, functional units of ovaries containing progressively developing egg chambers. The anterior-most structure of ovarioles, named germarium, has at its anterior tip terminal filament cells and cap cells that form the GSC niche, which houses two or three GSCs. Each GSC contains a membranous-like structure, fusome, which is juxtaposed to the interface between cap cells and GSCs and its morphology changes periodically during GSC cell cycle progression. One GSC division produces two daughter cells, one daughter cell self-renews and the other one differentiates into the cystoblast, which undergoes four rounds of incomplete divisions interconnected by branched fusomes to form a germline cyst containing one oocyte, and fifteen nurse cells. Each germline cyst acquires a monolayer of follicle cells to form an egg chamber, which then buds off from the germarium and passes through fourteen developmental stages to become a mature egg. Despite its well-studied cell biology and powerful genetic tools, Drosophila is also a low-cost experimental animal, and easily cultured and manipulated under different environmental conditions. These advantages make Drosophila an ideal model system to study how stem cells react with their environments. Our research currently focuses on three aspects: Control of stem cell aging. Stem cell function/number is decline with age; however, mechanisms underlying this process are largely unknown. We, there, examine the features of aged stem cells at cellular levels. Establishment of GSC niche. The stem cell niche recruits and houses stem cells, including cancer stem cells; nevertheless, how stem cell niche established is largely unknown. We are currently characterizing 49 candidates obtained from a RNAi screening for niche establishment Impact of diet on GSCs. Diet influences Stem cells; however, not much known about the mechanisms involved. We are now analyze activities of several nutrient-sensing pathways, like insulin and mTOR signaling, that may directly or remotely control stem cells.
 
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