2021/12 – Present: Professor and Investigator, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China

2020/07 – 2021/11: Tenure-track Assistant Professor, University of Utah School of Medicine, Salt Lake City, USA

2018/08 – 2020/07: Postdoctoral researcher, University of Utah School of Medicine, Salt Lake City, USA

2013/08 – 2018/06: Ph.D., Oncological Sciences, University of Utah, Salt Lake City, USA (Advisor: Dr. Bradley Cairns)

2013/08 – 2016/05: Graduate Certificate in Genome Science, University of Utah, Salt Lake City, USA

2009/09 – 2013/07: B.S., Biological Sciences, Peking University, Beijing, China

1. Regulatory Mechanisms of Germ Cell and Gonadal Development

The research focuses on the regulation of development and differentiation in human spermatogonial stem cells (SSCs). By identifying a previously unrecognized human-specific SSC subtype and proposing a bidirectional, reversible developmental model, the work defines key molecular targets for SSC in vitro expansion and directed differentiation. Through a systematic characterization of testicular development from early embryogenesis through puberty to adulthood, it delineates the complete establishment of the SSC pool. In addition, the coordinated developmental interplay between germ cells and somatic cells of the testicular microenvironment is elucidated, providing a conceptual framework for improving fertility preservation strategies in adolescent cancer patients.

2. In Vitro Disease Modeling and Mechanistic Investigation

To overcome a major limitation in studying testosterone deficiency, male infertility, and associated metabolic disorders—the lack of in vitro systems that faithfully recapitulate the complex testicular microenvironment and its dynamic endocrine regulation—this research integrates developmental biology principles with organ-on-chip and cell engineering technologies to establish a biomimetic testicular organoid-on-chip platform. By reconstructing both physiological and pathological testicular niches in vitro, this work systematically dissects the cellular and molecular basis of male infertility. These findings demonstrate that spermatogenic failure in cryptorchidism primarily arises from SSC impairment and dysfunction of the spermatogenic niche. Notably, immune-related alterations, especially increased mast cell infiltration and degranulation, are identified as key contributing factors, providing a foundation for precision diagnostics and targeted therapeutic strategies.

3. AI-Driven Precision Decision-Making in Medicine

By generating 3D digital models of early human embryos, this research maps the molecular trajectories of critical developmental processes, including primordial germ cells specification, origin, migration, and gonadal primordium formation. These findings offer clinically relevant insights into the mechanisms underlying early developmental disorders. Leveraging large-scale, multicenter clinical datasets and machine learning approaches, we developed SpermFinder, a predictive tool for assessing outcomes of microdissection testicular sperm extraction (micro-TESE) in patients with non-obstructive azoospermia (NOA). This online platform (https://huggingface.co/spaces/SpermFinder/TESE) enables accurate estimation of sperm retrieval probability, supporting preoperative evaluation and informed clinical decision-making.

（#co-first author, *corresponding author）

1. Zhang W^#, Hong K^#, Tang Y, Cui L, Lu X, Cheng J, Fang Y, Jiang Q, Zhuang Z, Gao S, Jiang H, Liu Q*, Guo J*, Zhang Z*, Wang X*. Endothelial PDGF signaling dysregulation impairs testicular interstitial homeostasis in diabetes. Advanced Science. 2026 Jan 28.
2. Cui L^#, Lu X^#, Cai H, Zhuang Z, Guo Y, Jiang Q, Zhang Z*, Jiang H*, Wang X*, Guo J*. SPARK: A webserver for comprehensive search and analysis of testicular single-cell transcriptomic data covering full lifecycle and pathology. iMetaOmics. 2026 Jan 10:e70073.
3. Zhang B^#, Zhao X^#, Cao J, Liu Z, Wang X, Li R, Bo H, Xu K*, Guo J*. Single-cell atlas of human penile corpus cavernosum reveals cellular and functional heterogeneity of aging-related erectile dysfunction. Front Endocrinol (Lausanne). 2025 Oct 29;16:1671482.
4. Xi Y^#, Zhang B^#, Zhang Y^#, Zhao L, Liu D, Mao J, Tang W, Zhang H, Lin H, Wang X, Ren P, Tang Y, Yang Y, Hong K*, Guo J*, Zhang Z*, Jiang H*. Machine learning-based personalized prediction of sperm retrieval in patients with non-obstructive azoospermia prior to microdissection testicular sperm extraction: A multi-center cohort study. Andrology. 2025 Sep 8.
5. Ba Omar H^#, Stevens J^#, Haavisto A, Cui Y, Harteveld F, Yang Y, Bjarnason R, Romerius P, Sundin M, Nyström UN, Langenskiöld C, Vogt H, Frisk P, Vepsäläinen K, Petersen C, Cui L, Guo J, Jahnukainen K*, Stukenborg JB*. Early transcriptional states of spermatogonia and marker expressions in the prepubertal human testis following chemotherapy-induced depletion. Hum Reprod. 2025 Aug 1;40(8):1467-1475.
6. Yuan Y^#, Wang X^#, Yan X^#, He N^#, Lu X^#, Yang J^#, Xie X^#, Yuan H, Chen N, Liu Y, Ren H, Zhang R, Cui L, Ren P, Lin S, Cheng S, Yang X, Guo Y, Li R, Yan T, Guo J*, Xiao Z*, Wei Y*, Yu L*.3D reconstruction of a human Carnegie stage 9 embryo provides a snapshot of early body plan formation. Cell Stem Cell. 2025 Jun 5.
7. 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 Apr;5(4):658-674.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. Wang X, Cairns BR*, Guo J*. When spermatogenesis meets human aging and elevated body mass. Life Med. 2022 Jul 9;1(3):267-269.
20. 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.
21. 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.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. 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.