The ultimate goal of our lab is to gain a better understanding of male germline stem cell and utilize that knowledge to better diagnose and treat male infertility. In recent years, the Guo lab took advantage of the cutting-edge single-cell genomics profiling approaches and made several impactful discoveries on human germline stem cell and testis development. For instance, we identified a novel type of human spermatogonial stem cells (SSCs), termed State 0. We delineated the molecular mechanisms underlying how State 0 SSCs originate in the fetal testis, and how they undergo differentiation to generate sperm. We also uncovered how somatic differentiation guide the differentiation of germ cells through development. We have published over 20 papers in high-impact journals, including Cell Stem Cell, Nature Genetics, Cell Research, American Journal of Human Genetics etc.

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 germ cell development.

Plain english:
My lab has three major research focuses. First, we utilize a combination of cutting-edge genomics and molecular techniques to understand the normal development and physiology of human germline and testis. Second, we want to develop novel molecular and computational tools to diagnose human male infertility and germ cell tumor more precisely, aiming to offer better treatment for the patients. Last, we are interested to utilize the knowledge learned from our research to establish novel in vivo and in vitro models to better study human SSCs and germline.

Selected publications:

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)