研究领域

本课题组主要研究领域为胚胎植入的生理病理机制。利用多种转基因、组织特异性基因敲除小鼠模型，结合体外子宫细胞培养、类器官和多种生化分子手段，致力于1）揭示子宫接受态的建立、囊胚激活及二者协同对话的分子机制。2）雌、孕激素受体在围植入期子宫内膜分化中的作用网络。近期在Nature Communications、PNAS、eLife、Journal of Clinical Investigation等国际学术期刊上发表系列研究论文，从囊胚获得植入能力和子宫内膜分化进入容受态等角度，阐释了多个调控胚胎植入的关键分子。

学习经历

2004-2008西北大学生命科学学院 生物科学专业 理学学士

2008-2014中国科学院大学 发育生物学 博士

工作经历

2022.11-至今 yl23411永利官网登录 教授

2021.08-2022.10 yl23411永利官网登录 副教授

2016.06-2021.07 yl23411永利官网登录 助理教授

2014.07-2016.05 中国科学院动物研究所 博士后

代表性成果

1. Tang Y, Qiu J, Tang Z, Li G, Gu M, Wang Y, Bao H, Deng W, Lu Z, Otsu K, Wang Z*, Wang H*, Kong S*. P38α MAPK is a gatekeeper of uterine progesterone responsiveness at peri-implantation via Ube3c-mediated PGR degradation. Proc Natl Acad Sci U S A. 2022 Aug 9;119(32):e2206000119.

2. Liu MY, Deng W, Tang L, Liu M, Bao H, Guo C, Zhang C, Lu J, Wang H*, Lu Z*, Kong S*. Menin directs regionalized decidual transformation through epigenetically setting PTX3 to balance FGF and BMP signaling. Nat Commun. 2022. 13:1006.

3. Huang P, Deng W, Bao H, Lin Z, Liu M, Wu J, Zhou X, Qiao M, Yang Y, Cai H, Rao F, Chen J, Chen D, Lu J, Wang H*, Qin A*, Kong S*. SOX4 facilitates PGR protein stability and FOXO1 expression conducive for human endometrial decidualization. Elife. 2022 Mar 4;11:e72073.

4. Zhou C, Lv M, Wang P, Guo C, Ni Z, Bao H, Tang Y, Cai H, Lu J, Deng W, Yang X, Xia G, Wang H*, Wang C*, Kong S*. Sequential activation of uterine epithelial IGF1R by stromal IGF1 and embryonic IGF2 directs normal uterine preparation for embryo implantation. J Mol Cell Biol. 2021 Jun 7;mjab034.

5. Cheng J, Liang J, Li Y, Gao X, Ji M, Liu M, Tian Y, Feng G, Deng W, Wang H*, Kong S*, Lu Z*. Shp2 in uterine stromal cells critically regulates on time embryo implantation and stromal decidualization by multiple pathways during early pregnancy. PLoS Genet. 2022 Jan 13;18(1):e1010018.

6. Bao H, Sun Y, Yang N, Deng N, Ni Z, Tang Y, Li G, Du L, Wang Y, Chen D*, Wang H*, Kong S*. Uterine Notch2 facilitates pregnancy recognition and corpus luteum maintenance via upregulating decidual Prl8a2. PLoS Genet. 2021. 17(8): e1009786.

7. Jiang Y, Li J, Li G, Liu S, Lin X, He Y, Lu J, Zhang Y, Wu J, Yang Z, Jiang Y, Wang H*, Kong S*, Shi G*. Osteoprotegerin interacts with syndecan-1 to promote human endometrial stromal decidualization by decreasing Akt phosphorylation. Hum Reprod. 2020 Nov 1;35(11):2439-2453.

8. He B#, Zhang H#, Wang J, Liu M, Sun Y, Guo C, Lu J, Wang H*, Kong S*. Blastocyst activation engenders transcriptome reprogram affecting X-chromosome reactivation and inflammatory trigger of implantation. Proc Natl Acad Sci U S A. 2019. 116(33): 16621-16630.

9. Zhang Y, Meng N, Bao H, Jiang Y, Yang N, Wu K, Wu 3, Wang H, Kong S*, Zhang Y*. Circadian gene PER1 senses progesterone signal during human endometrial decidualization. J Endocrinol. 2019. 243, 229–242.

10. Kong S, Zhou C, Bao H, Ni Z, Liu M, He B, Huang L, Sun Y, Wang H*, Lu J*. Epigenetic control of embryo-uterine crosstalk at peri-implantation. Cell Mol Life Sci. 2019. Jul 27. doi: 10.1007/s00018-019-03245-8.

11. Xin Q#, Kong S#, Yan J#, Qiu J, He B, Zhou C, Ni Z, Bao H, Huang L, Lu J, Xia G, Liu X*, Chen Z*, Wang C*, Wang H*. Polycomb subunit BMI1 determines uterine progesterone responsiveness essential for normal embryo implantation. J Clin Invest. 2018 Jan 2;128(1):175-189. doi: 10.1172/JCI92862.

12. Kong S#, Liang G#, Tu Z, Chen D, Wang H*, Lu J*. Generation of Elf5-Cre knockin mouse strain for trophoblast-specific gene manipulation. Genesis. 2018 Apr;56(4):e23101. doi: 10.1002/dvg.23101.

在研的重要课题

1. 国家自然基金优秀青年基金，01/2023-12/2025，，200万，主持。

2. 国家自然基金面上项目，01/2023-12/2026，54万，主持。

3. 国家自然基金面上项目，01/2020-12/2023，55万，主持。

4. 国家重点研发计划“生育健康及妇女儿童健康保障”重点专项12/2022-11/2025，65万，项目骨干。

所有论文列表

1. Liu, M., et al., Menin directs regionalized decidual transformation through epigenetically setting PTX3 to balance FGF and BMP signaling. Nat Commun, 2022. 13(1): p. 1006.

2. Tang, Y., et al., P38alpha MAPK is a gatekeeper of uterine progesterone responsiveness at peri-implantation via Ube3c-mediated PGR degradation. Proc Natl Acad Sci U S A, 2022. 119(32): p. e2206000119.

3. Huang, P., et al., SOX4 facilitates PGR protein stability and FOXO1 expression conducive for human endometrial decidualization. Elife, 2022. 11.

4. Jiang, R., et al., CDC42 governs normal oviduct multiciliogenesis through activating AKT to ensure timely embryo transport. Cell Death Dis, 2022. 13(9): p. 757.

5. Wu, J., et al., Maternal anxiety affects embryo implantation via impairing adrenergic receptor signaling in decidual cells. Commun Biol, 2022. 5(1): p. 840.

6. Cheng, J., et al., Shp2 in uterine stromal cells critically regulates on time embryo implantation and stromal decidualization by multiple pathways during early pregnancy. PLoS Genet, 2022. 18(1): p. e1010018.

7. Yu, Y., et al., Adgrg1 is a new transcriptional target of Hand1 during trophoblast giant cell differentiation. J Reprod Immunol, 2022. 154: p. 103753.

8. Wang, Z., et al., Ablation of the miR-465 Cluster Causes a Skewed Sex Ratio in Mice. Front Endocrinol (Lausanne), 2022. 13: p. 893854.

9. Ma, W., et al., MAX deficiency impairs human endometrial decidualization through down-regulating OSR2 in women with recurrent spontaneous abortion. Cell Tissue Res, 2022. 388(2): p. 453-469.

10. Lou, L., et al., Human Endometrial Organoids: Recent Research Progress and Potential Applications. Front Cell Dev Biol, 2022. 10: p. 844623.

11. Zhou, C., et al., Sequential activation of uterine epithelial IGF1R by stromal IGF1 and embryonic IGF2 directs normal uterine preparation for embryo implantation. J Mol Cell Biol, 2021. 13(9): p. 646-661.

12. Bao, H., et al., Uterine Notch2 facilitates pregnancy recognition and corpus luteum maintenance via upregulating decidual Prl8a2. PLoS Genet, 2021. 17(8): p. e1009786.

13. Zhou, X., et al., Single-cell RNA-seq revealed diverse cell types in the mouse placenta at mid-gestation. Exp Cell Res, 2021. 405(2): p. 112715.

14. Wu, J.X., S. Lin, and S.B. Kong, Psychological Stress and Functional Endometrial Disorders: Update of Mechanism Insights. Front Endocrinol (Lausanne), 2021. 12: p. 690255.

15. Xu, Y., et al., HOXA10 co-factor MEIS1 is required for the decidualization in human endometrial stromal cell. J Mol Endocrinol, 2020. 64(4): p. 249-258.

16. Jiang, Y., et al., Osteoprotegerin interacts with syndecan-1 to promote human endometrial stromal decidualization by decreasing Akt phosphorylation. Hum Reprod, 2020. 35(11): p. 2439-2453.

17. Bao, H., et al., Hyperactivated Wnt-beta-catenin signaling in the absence of sFRP1 and sFRP5 disrupts trophoblast differentiation through repression of Ascl2. BMC Biol, 2020. 18(1): p. 151.

18. Zhou, Q., et al., EHD1 impairs decidualization by regulating the Wnt4/beta-catenin signaling pathway in recurrent implantation failure. EBioMedicine, 2019.

19. Zhang, Y., et al., Circadian gene PER1 senses progesterone signal during human endometrial decidualization. J Endocrinol, 2019.

20. Zhang, S., et al., Implantation initiation of self-assembled embryo-like structures generated using three types of mouse blastocyst-derived stem cells. Nat Commun, 2019. 10(1): p. 496.

21. Wu, J., et al., An exaggerated epinephrine-adrenergic receptor signaling impairs uterine decidualization in mice. Reprod Toxicol, 2019. 90: p. 109-117.

22. Sha, Y., et al., Biallelic mutations in Sperm flagellum 2 cause human multiple morphological abnormalities of the sperm flagella (MMAF) phenotype. Clin Genet, 2019. 96(5): p. 385-393.

23. Lu, J., et al., Spatiotemporal coordination of trophoblast and allantoic Rbpj signaling directs normal placental morphogenesis. Cell Death Dis, 2019. 10(6): p. 438.

24. Li, Y., et al., DNAH2 is a novel candidate gene associated with multiple morphological abnormalities of the sperm flagella. Clin Genet, 2019. 95(5): p. 590-600.

25. Li, Y., et al., The role of tyrosine phosphatase Shp2 in spermatogonial differentiation and spermatocyte meiosis. Asian J Androl, 2019.

26. Kong, S., et al., Epigenetic control of embryo-uterine crosstalk at peri-implantation. Cell Mol Life Sci, 2019.

27. Huang, L., et al., Traditional Chinese medicine Dingkun Pill facilitates uterine receptivity for implantation in micedagger. Biol Reprod, 2019. 101(4): p. 695-703.

28. He, B., et al., Blastocyst activation engenders transcriptome reprogram affecting X-chromosome reactivation and inflammatory trigger of implantation. Proc Natl Acad Sci U S A, 2019. 116(33): p. 16621-16630.

29. Gao, Y., et al., Ubiquitin-specific protease 7 (USP7) is essential for endometrial stromal cell decidualization in mice. Dev Growth Differ, 2019. 61(2): p. 176-185.

30. Xin, Q., et al., Polycomb subunit BMI1 determines uterine progesterone responsiveness essential for normal embryo implantation. J Clin Invest, 2018. 128(1): p. 175-189.

31. Kong, S., et al., Generation of Elf5-Cre knockin mouse strain for trophoblast-specific gene manipulation. Genesis, 2018. 56(4): p. e23101.

32. Xin, Q., et al., Transcript analysis identifies differential uterine gene expression profile beyond the normal implantation window in mice. Theriogenology, 2017. 104: p. 55-61.

33. Ran, H., et al., Nuclear Shp2 directs normal embryo implantation via facilitating the ERalpha tyrosine phosphorylation by the Src kinase. Proc Natl Acad Sci U S A, 2017. 114(18): p. 4816-4821.

34. Cui, T., et al., PR-Set7 deficiency limits uterine epithelial population growth hampering postnatal gland formation in mice. Cell Death Differ, 2017. 24(12): p. 2013-2021.

35. Wu, W., et al., Spatiotemporal expression of endogenous opioid processing enzymes in mouse uterus at peri-implantation. Cell Tissue Res, 2016. 363(2): p. 555-65.

36. Tu, Z., et al., Uterine RAC1 via Pak1-ERM signaling directs normal luminal epithelial integrity conducive to on-time embryo implantation in mice. Cell Death Differ, 2016. 23(1): p. 169-81.

37. Kong, S., et al., MCM2 mediates progesterone-induced endometrial stromal cell proliferation and differentiation in mice. Endocrine, 2016. 53(2): p. 595-606.

38. Jiang, Y., et al., Uterine Prx2 restrains decidual differentiation through inhibiting lipolysis in mice. Cell Tissue Res, 2016. 365(2): p. 403-14.

39. Tang, X., et al., Systemic morphine treatment derails normal uterine receptivity, leading to embryo implantation failure in mice. Biol Reprod, 2015. 92(5): p. 118.

40. Jiang, Y., et al., FoxM1 Directs STAT3 Expression Essential for Human Endometrial Stromal Decidualization. Sci Rep, 2015. 5: p. 13735.

41. He, H., et al., Rbbp7 Is Required for Uterine Stromal Decidualization in Mice. Biol Reprod, 2015. 93(1): p. 13.

42. Zhang, S., et al., Uterine Rbpj is required for embryonic-uterine orientation and decidual remodeling via Notch pathway-independent and -dependent mechanisms. Cell Res, 2014. 24(8): p. 925-42.

43. Fu, Z., et al., Integral proteomic analysis of blastocysts reveals key molecular machinery governing embryonic diapause and reactivation for implantation in mice. Biol Reprod, 2014. 90(3): p. 52.

44. Chen, Y., et al., Preimplantation mouse embryo is a target for opioid ligand-receptor signaling. Biol Reprod, 2014. 91(1): p. 4.

45. Zhang, S., et al., Physiological and molecular determinants of embryo implantation. Mol Aspects Med, 2013. 34(5): p. 939-80.

46. Zhang, S., et al., Deciphering the molecular basis of uterine receptivity. Mol Reprod Dev, 2013. 80(1): p. 8-21. Lu, J., et al., A positive feedback loop involving Gcm1 and Fzd5 directs chorionic branching morphogenesis in the placenta. PLoS Biol, 2013. 11(4): p. e1001536.

47. Kong, S., et al., Determinants of uterine aging: lessons from rodent models. Sci China Life Sci, 2012. 55(8): p. 687-93.