本研究组的终极目标是希望通过对人类的生殖干细胞进行更加深入地了解，从而以此为基础进行雄性不育的诊断与治疗。近些年来，我们利用最新的单细胞高通量测序，在生殖细胞和睾丸发育的领域上做出了很多突出贡献。例如，我们发现了一类人类特有的生殖干细胞并命名为State 0。我们还系统性地阐述了成年人体内的State 0干细胞是如何从胚胎里面分化出来的，又是如何继续向后分化源源不断地产生精子的。同时，我们还发现了睾丸内体细胞的发育成熟伴随且引导着生殖细胞的发育而成熟的分子过程。迄今为止，我们已经在各类高影响力的国际期刊上发表了超过20篇文章，其中包括 Cell Stem Cell, Nature Genetics, Cell Research, American Journal of Human Genetics 等。

Goals and approaches of our research.

A transcriptional single-cell atlas of the fetal and postnatal human testes. We uncovered how adult SSCs originate from the fetal PGCs, and how somatic differentiation accompanies and guides human fetal germ cell development.

研究内容和目标:
本研究组主要有三个研究重点。第一，我们利用最新的测序和分子生物学技术来研究人类生殖细胞和睾丸发育的正常过程。第二，我们希望建立起全新的分子生物学和计算方法，来对雄性不育进行更好、更精确地诊断与治疗。第三，我们希望利用所获得的的知识，发展出新的体内和体外的模型来更好地模拟研究人类精原干细胞。

代表性发表论文:

1. Lu X^#, Luo Y^#, Nie X, Zhang B, Wang X, Li R, Liu G, Zhou Q, Liu Z, Fan L, Hotaling JM, Zhang Z*, Bo H*, Guo J*. Single-cell multi-omics analysis of human testicular germ cell tumor reveals its molecular features and microenvironment. Nat Commun. (2023)14(1):8462.
2. Wamaitha SE^#, Nie X^#, Pandolfi EC, Wang X, Yang Y, Stukenborg JB, Cairns BR, Guo J*, Clark AT*. Single-cell analysis of the developing human ovary defines distinct insights into ovarian somatic and germline progenitors. Dev Cell. (2023)58(20):2097-2111.e3.
3. Nie X, Munyoki SK, Sukhwani M, Schmid N, Missel A, Emery BR, DonorConnect, Stukenborg JB, Mayerhofer A, Orwig KE, Aston KI, Hotaling JM, Cairns BR^*, Guo J*. Single-cell analysis of human testis aging and correlation with elevated body mass index. Dev Cell (2022)57(9): 1160-1176.
4. Mahyari E^#, Guo J ^#,*, Lima AC, Vigh-Conrad KA,  Nie X, Nagirnaja L, Rockweiler N, Carrell DT, Hotaling JM, Aston KI, Conrad DF*. Comparative Single-Cell Analysis of Biopsies Clarifies Pathogenic Mechanisms in Klinefelter Syndrome. American Journal of Human Genetics. (2021) 108(10):1924-1945.
5. Guo J ^*, Sosa E, Chitiashvili T, Nie X, Rojas EJ, Oliver E, DonorConnect, Hotaling JM, Stukenborg J, Clark AT*, Cairns BR*. Single-Cell Analysis of the Developing Human Testis Reveals Somatic Niche Cell Specification and Fetal Germline Stem Cell Establishment. Cell Stem Cell. (2021) 28(4):764-778.
6. Murphy PJ^#, Guo J ^#, Jenkins TG, James ER, Hoidal JR, Huecksteadt J, Hotaling JM, Carrell DT, Cairns BR, Aston KI. NRF2 Loss Recapitulates Heritable Impacts of Paternal Cigarette Smoke Exposure. PLOS Genetics (2020) 16(6):e1008756.
7. Pan F^#, Xiao X^#, Guo J ^#, Song Y^#, Li H^#, Patel DP, Spivak AM, Alukal JP, Zhang X, Xiong C, Li PS, Hotaling JM. No Evidence of SARS-CoV-2 in Semen of Males Recovering from COVID-19. Fertility and Sterility (2020) 113(6):1135-1139.
8. Guo J , Nie X, Giebler M, Mlcochova H, Wang Y, Grow EJ, DonorConnect, Kim R, Tharmaligham M, Matilionyte G, Mitchell RT, Lindskog L, Carrell DT, Goriely A, Hotaling JM, Cairns BR. The Dynamic Transcriptional Cell Atlas of Testis Development During Human Puberty. Cell Stem Cell (2020) 26(2): 262-276.
9. Guo J , Grow EJ, Mlcochova H, Maher GJ, Lindskog C, Nie X, Guo Y, Takei Y, Yun J, Cai L, Kim R, Carrell DT, Goriely A, Hotaling JM, Cairns BR. The Adult Human Testis Transcriptional Cell Atlas. Cell Research (2018) 28: 1141-1157.
10. Guo J , Grow EJ, Yi C, Mlcochova H, Maher GJ, Lindskog C, Murphy PJ, Wike CL, Carrell DT, Goriely A, Hotaling JM, Cairns BR. Chromatin and Single-Cell RNA-seq Profiling Reveal Dynamic Signaling and Metabolic Transitions during Human Spermatogonial Stem Cell Development. Cell Stem Cell (2017) 21(4): 533-546.

(# Co-first, * Corresponding)