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郭靖涛,研究员

干细胞与性腺发育

Email:jingtao.guo@ioz.ac.cn

欢迎您加入干细胞与性腺发育研究组
-副研究员:王晓琰
-工作人员:朱倩文
-博士后:岳静伟、崔利娜
-博士研究生:章百灵、卢晓健、张文秀、苗鹤凡、郭一菲、蔡卉、李冉、庄子研
-硕士研究生:关施旗、李杨、蒋巧玲、任鹏程、刘昱雯、党晨欣

实验室主页:https://guolab.info

 

  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. Cui L#, Nie X#, Guo YX#, Ren P, Guo YF, Wang X, Li R, Hotaling JM, Cairns BR*, Guo J*. Single-cell transcriptomic atlas of human testis across the reproductive lifespan. Nature Aging. 2025 Mar 3. (On Line)
  2. Jiang Q, Cui L, Nie X, Cai H, Zhang W, Lu X, Guo Y, Hotaling JM, Cairns BR, Wang X*, Guo J*. A single-cell transcriptome atlas characterizes the immune landscape of human testes during aging. Aging Cell. 2025 Mar 6;e70032.
  3. Cui L#, Lin S#, Yang X#, Xie X#, Wang X#, He N#, Yang J, Zhang X, Lu X, Yan X, Guo Y, Zhang B, Li R, Miao H, Ji M, Zhang R, Yu L*, Xiao Z*, Wei Y*, Guo J*. Spatial transcriptomic characterization of a Carnegie stage 7 human embryo. Nat Cell Biol. 2025 Feb;27(2):360-369.
  4. Wang X#, Cheng L#, Lu X#, Jin H#, Cui L, Guo Y, Guo J*, Xu EY*. Cross-species comparative single-cell transcriptomics highlights the molecular evolution and genetic basis of male infertility. Cell Rep. 2024 Dec 30;44(1):115118.
  5. Wang X#, Wang Y#, Wang Y#, Guo Y#, Zong R, Hu S, Yue J, Yao J, Han C*, Guo J*, Zhao J*. Single-cell transcriptomic and cross species comparison analyses reveal distinct molecular changes of porcine testes during puberty. Commun Biol. 2024 Nov 9;7(1):1478.
  6. Wang X#, Liu Q#, Zhuang Z#, Cheng J, Zhang W, Jiang Q, Guo Y, Li R, Lu X, Cui L, Weng J, Tang Y, Yue J, Gao S, Hong K, Qiao J, Jiang H*, Guo J*, Zhang Z*. Decoding the pathogenesis of spermatogenic failure in cryptorchidism through single-cell transcriptomic profiling. Cell Rep Med. 2024 Sep 17;5(9):101709.
  7. Cui Y, Harteveld F, Ba Omar HAM, Yang Y, Bjarnason R, Romerius P, Sundin M, Norén Nyström U, Langenskiöld C, Vogt H, Henningsohn L, Frisk P, Vepsäläinen K, Petersen C, Mitchell RT, Guo J, Alves-Lopes JP, Jahnukainen K, Stukenborg JB. Prior exposure to alkylating agents negatively impacts testicular organoid formation in cells obtained from childhood cancer patients. Hum Reprod Open. 2024 Aug 13;2024(3):hoae049.
  8. Xiao Z#, Cui L#, Yuan Y#, He N#, Xie X, Lin S, Yang X, Zhang X, Shi P, Wei Z, Li Y, Wang H, Wang X*, Wei Y*, Guo J*, Yu L*. 3D reconstruction of a gastrulating human embryo. Cell. 2024 May 23;187(11):2855-2874.e19.
  9. 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 Dec 20;14(1):8462.
  10. 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 Oct 23;58(20):2097-2111.e3.
  11. Matilionyte G, Forsyth G, Guo J, Rimmer MP, Hermann BP, Anderson RA, Mitchell RT. Granulocyte-colony stimulating factor does not prevent in vitro cisplatin-induced germ cell reduction in immature human and mouse testis.  BMC Cancer. 2023 Mar 16 ;23(1):251.
  12. 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 May 9;57(9):1160-1176.e5.
  13. Wang X, Cairns BR*, Guo J*. When spermatogenesis meets human aging and elevated body mass. Life Med. 2022 Jul 9;1(3):267-269.
  14. Mahyari E#, Guo J#*, Lima AC, Lewinsohn DP, Stendahl AM, Vigh-Conrad KA, Nie X, Nagirnaja L, Rockweiler NB, Carrell DT, Hotaling JM, Aston KI, Conrad DF*. Comparative single-cell analysis of biopsies clarifies pathogenic mechanisms in Klinefelter syndrome. Am J Hum Genet. 2021 Oct 7;108(10):1924-1945.
  15. Patel DP, Punjani N, Guo J, Alukal JP, Li PS, Hotaling JM*. The impact of SARS-CoV-2 and COVID-19 on male reproduction and men's health. Fertil Steril. 2021 Apr;115(4):813-823.
  16. Guo J*, Sosa E, Chitiashvili T, Nie X, Rojas EJ, Oliver E; DonorConnect; Plath K, Hotaling JM, Stukenborg JB, 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 Apr 1;28(4):764-778.e4.
  17. Tharmalingam MD, Matilionyte G, Wallace WHB, Stukenborg JB, Jahnukainen K, Oliver E, Goriely A, Lane S, Guo J, Cairns B, Jorgensen A, Allen CM, Lopes F, Anderson RA, Spears N, Mitchell RT. Cisplatin and carboplatin result in similar gonadotoxicity in immature human testis with implications for fertility preservation in childhood cancer. BMC Med. 2020 Dec 4 ;18(1):374.
  18. Murphy PJ#*, Guo J#, Jenkins TG, James ER, Hoidal JR, Huecksteadt T, Broberg DS, Hotaling JM, Alonso DF, Carrell DT, Cairns BR*, Aston KI*. NRF2 loss recapitulates heritable impacts of paternal cigarette smoke exposure. PLoS Genet. 2020 Jun 10;16(6):e1008756.
  19. Guo J, Nie X, Giebler M, Mlcochova H, Wang Y, Grow EJ; DonorConnect; Kim R, Tharmalingam M, Matilionyte G, Lindskog C, Carrell DT, Mitchell RT, Goriely A, Hotaling JM, Cairns BR*. The Dynamic Transcriptional Cell Atlas of Testis Development during Human Puberty. Cell Stem Cell. 2020 Feb 6;26(2):262-276.e4.
  20. Guo J*, Cairns BR. Isolation and Enrichment of Spermatogonial Stem Cells From Human Testis Tissues. Curr Protoc Stem Cell Biol. 2019 Jun;49(1):e77.
  21. 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 Res. 2018 Dec;28(12):1141-1157.
  22. 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 Oct 5;21(4):533-546.e6.

(# Co-first, * Corresponding)