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　　成體組織中存在著能夠自我更新、有多種分化潛能的細(xì)胞稱成體干細(xì)胞。成體干細(xì)胞對(duì)器官的發(fā)育、自穩(wěn)態(tài)維持有至關(guān)重要的作用，還有可能是癌癥發(fā)生的細(xì)胞靶點(diǎn)。成體干細(xì)胞領(lǐng)域的挑戰(zhàn)是：1)許多器官成體干細(xì)胞的身份屬性并不清楚;2)成體干細(xì)胞一旦離開了體內(nèi)的微環(huán)境信號(hào)，在體外不能維持干細(xì)胞的特性(干性)，并且干細(xì)胞的數(shù)量難以在體外擴(kuò)增，使得相關(guān)的分子機(jī)制研究難以進(jìn)行。針對(duì)這些挑戰(zhàn)和機(jī)遇，實(shí)驗(yàn)室的近期目標(biāo)一是發(fā)現(xiàn)成體干細(xì)胞的身份屬性，尤其是干細(xì)胞表面的特異標(biāo)記分子，能夠富集并分離得到活體的干細(xì)胞;目標(biāo)二是發(fā)現(xiàn)成體干細(xì)胞的微環(huán)境因子，使得成體干細(xì)胞在體外能夠長(zhǎng)期培養(yǎng)和擴(kuò)增，并保持干性。

　　實(shí)驗(yàn)室主要以小鼠乳腺為組織模型，運(yùn)用原代干細(xì)胞培養(yǎng)、基因操縱等體外實(shí)驗(yàn)，結(jié)合干細(xì)胞移植、構(gòu)建轉(zhuǎn)基因及基因敲除小鼠、損傷修復(fù)、譜系示蹤等體內(nèi)實(shí)驗(yàn)手段，研究成體干細(xì)胞的屬性及調(diào)控機(jī)制。實(shí)驗(yàn)室近期的研究方向包括：

　　1) 發(fā)現(xiàn)各器官中成體干細(xì)胞的身份屬性，包括乳腺、卵巢、血管、胰腺等;

　　2) 通過(guò)對(duì)比各成體干細(xì)胞，闡明干細(xì)胞“干性”的分子組成;

　　3) 發(fā)現(xiàn)成體干細(xì)胞新的微環(huán)境因子，闡明其調(diào)控干細(xì)胞的分子機(jī)理;

　　4) 研究干細(xì)胞關(guān)鍵調(diào)控分子在再生醫(yī)學(xué)、癌癥治療中的調(diào)控變化。

　　實(shí)驗(yàn)室的長(zhǎng)遠(yuǎn)目標(biāo)是闡明干細(xì)胞的分子調(diào)控機(jī)理，為癌癥治療和再生醫(yī)學(xué)提供新的策略。

1. Yu QC, Verheyen EM,Zeng YA*. Mammary Development and Breast Cancer: A Wnt Perspective. Cancers. Jul 13;8(7).pii: E65. doi: 10.3390/cancers8070065. (2016)
2. Yu QC, Song W, Wang D, Zeng YA*. Identification of blood vascular endothelial stem cells by the expression of protein C receptor. Cell Research. Jul 1. doi: 10.1038/cr.2016.85. (2016)
3. Zeng L+, Cai C+, Li S, Yu QC, Wang W, Li Y, Chen J, Zhu X*, Zeng YA*. Essential roles of Cyclin Y-like 1 and Cyclin Y in dividing Wnt-responsive mammary stem/progenitor cells. PLOS Genetics. May 20;12(5):e1006055 (2016)
4. WANGD+, Zeng YA*. Identification of Multipotent Mammary Stem Cells by Protein C Receptor Expression. Nature. Jan 1;517(7532):81-4 (2015)
5. Cai C, Yu QC, Jiang W, Liu W, Song W, Yu H, Zhang L, Yang Y, Zeng YA*. R-spondin1 is a novel hormone mediator for mammary stem cell self-renewal. Genes Dev. Sep 26;28: 2205–2218 (2014)
6. Harburg G, Compton J, Liu W, Iwai N, Zada S, Marlow R, Strickland P, Zeng YA, Hinck L. SLIT/ROBO2 Signaling Promotes Mammary Stem Cell Senescence by Inhibiting Wnt Signaling. Stem Cell Reports. Sep 9;3(3):385-93 (2014)
7. Jan TA, Chai R, Sayyid ZN, van Amerongen R, Xia A, Wang T, Sinkkonen ST, Zeng YA, Levin JR, Heller S, Nusse R, Cheng AG. Tympanic border cells are Wnt-responsive and can act as progenitors for postnatal mouse cochlear cells. Development. Mar;140(6):1196-206 (2013)
8. Zeng YA*. Beyond nutrients and bonding: p63-positive progenitors in breast milk. Cell Cycle. Feb 15;10(4):579-8 (2011)
9. Zeng YA and Nusse R*. Wnt proteins serve as self-renewal factors for mammary stem cells and promote their long-term expansion in culture. Cell Stem Cell. Jun 4;6(6):568-77 (2010)
10. Minear S, Leucht P, Jiang J, Liu B, Zeng A, Fuerer C, Nusse R, and Helms JA. Wnt proteins promote bone regeneration. Science Translational Medicine. Apr; 28;2(29):29ra30 (2010)
11. Nusse R, Fuerer C, Ching W, Harnish K, Logan C, Zeng A, Ten Berge D, Kalani Y. Wnt Signaling and Stem Cell Control. Cold Spring HarbSymp Quant Biol. ;73:59-66 (2008)
12. Zeng YA+, Rahnama M+, Wang S, Lee W, Verheyen EM*. Inhibition of Drosophila Wg signaling involves competition between Mad and Armadillo/beta-catenin for dTcf binding. PLoS ONE. Dec; 3(12):e3893 (2008)
13. Zeng YA+, Rahnama M+, Wang, Sosu-Sedzorme W, Verheyen EM*. Drosophila Nemo antagonizes BMP signaling by phosphorylation of Mad and inhibition of its nuclear accumulation.” Development. Jun; 134(11):2061-71 (2007)
14. Zeng YA and Verheyen EM*. Nemo is an inducible antagonist of Wingless signaling during Drosophila wing development.Development. Jun; 131(12):2911-20 (2004)