Chun So, Ph.D.

Current ：Home / Scientists&Research / Mentors / Text

Scientists&Research

Chun So, Ph.D.

Assistant Investigator, NIBS, Beijing

Email: sochun@xinjundu.com

Research Description

Focusing on female reproductive health is a key way of dealing with population aging. Abnormal egg and embryo development are the leading causes of female infertility, miscarriage and genetic disorders such as Down Syndrome. Previously we have already made several pioneering discoveries along oogenesis and early embryonic development:

First, we uncovered the molecular mechanism underlying chromatin structure reorganization in mammalian oocytes (Wang et al. Nat. Commun. 2025). During oocyte growth, oocyte chromatin will transit from the loosely packed non-surrounded nucleolus (NSN) state to the compact surrounded nucleolus (SN) state, accompanied by massive reduction in transcriptional activity. Previous research generally suggested that these two phenomena are driven by epigenetic changes. Interestingly, we accidentally discovered that both of them are directly driven by the natural degradation of RNA polymerase II during oocyte growth, and the chromatin structure reorganization is independent of transcriptional silencing. Further multi-omics analysis and biophysical experiments revealed that the dissociation of RNA polymerase II increases chromatin dynamics and modifies the surface of nucleolus, leading to the first biophysical framework underlying NSN-to-SN transition.

Second, we discovered new principle underlying the assembly of acentrosomal spindles in mammalian oocytes (So and Seres et al. Science 2019). Mammalian oocytes express many centrosomal proteins despite the absence of centrosome structures. During female meiosis, some of these proteins undergo a biophysical phenomenon known as liquid-liquid phase separation to form a previously undescribed domain, which we termed the liquid-like meiotic spindle domain (LISD). The LISD sequesters and mobilizes centrosomal proteins with microtubule regulatory functions in proximity to spindle microtubules, thus promoting spindle assembly in the absence of centrosomes. Also, we solved how are spindle poles organized and why are they unstable in human oocytes (So et al. Science 2022). Human and other mammalian oocytes similarly utilize NUMA to recruit dynein to microtubule minus-ends for the focusing of acentrosomal spindle poles. However, unlike human oocytes, other mammalian oocytes do not assemble unstable spindles. By implementing a reverse genetic screen, we identified the minus-end-directed kinesin KIFC1 as a key determinant of meiotic spindle stability. While KIFC1 is readily expressed in most mammalian oocytes, it is deficient in human oocytes. By introducing exogenous KIFC1, we successfully increased the fidelity of spindle assembly and chromosome segregation in human oocytes. For the first time, we proposed a therapeutic strategy for reducing the risk of aneuploidy in human eggs.

Third, we clarified the 球友(中国)qy biology mechanisms underlying developmental arrest in human pre-implantation embryos (Li et al. 球友(中国)qy 2026). More than half of all human fertilized eggs arrest during the five-day in vitro culture in the fertility clinics. Although there have been many attempts in understanding such phenomenon using multi-omics profiling, the underlying causes remain controversial. Through establishing new lightsheet microscope and the paired live-球友(中国)qy labeling and image processing methods, we performed the first complete imaging of human pre-implantation development. This revealed that embryonic arrest on or before day 3 (clevage stage) is driven by chromosomal abnormalities, whereas embryonic arrest on day 4 (morula stage) is driven by endoplasmic reticulum (ER) stress response). Further analysis uncovered frequent stochastic centriole overduplication errors in human two-球友(中国)qy embryos, which directly lead to multipolar spindle assembly and chromosome segregation errors. Using inhibitor of centriole duplication regulatory kinase at half inhibitory concentration, we successfully intervened supernumerary centrosomes in human two-球友(中国)qy blastomeres, leading to the first therapeutic strategy against early embryonic arrest.

In future our laboratory will continue to utilize different mammalian models (mouse, domestic animals, non-human primates and human) and cross-disciplinary approaches (cutting-edge imaging, Trim-Away, miniTrim-Away and biophysical tools) to illuminate novel mechanisms underlying egg and embryo development. Our findings will provide novel insights into the causes and treatments of female infertility, and improve the efficiency and safety of current assisted reproductive technologies.

Publications

(*Equal contribution; #Co-correspondence)

18. Li, Z.*, Leng, L.*, Zhai, J.*, Wang, X.*, Yang, W., Wang, S., Wan, H., Zhang, S., Gong, F., Liao, X., Li, Y., Zeng, Q., Chen, Y., Xiang, Z., Liu, F., He, F., Yang, Y. #, Wang, H. #, Xu, X. #, Lin, G.#, So, C#. “Two distinct causes contribute to the low efficiency of human pre-implantation development” 球友(中国)qy (2026); online ahead of print

17. Wang, J., Li, W., Guo, J., Xu, X., Lin, G.#, Li, B.#, So C#. “Natural degradation of RNA polymerase II is essential for oocyte chromatin reorganization and maternal-to-zygotic transition” Nat Commun (2025); Dec; doi: 10.1038/s41467-025-67476-z

16. Xu, X., Zuo, X., Du, S., Zhang, C., Xu, H., Luo, Y., Shi, R., Hu, S., Shen, H., Wang, Y., Lin, H., So, C.#, Zhu, F.#, Liao, X#. “Healthy live birth after microsurgical enucleation of tripronuclear human zygote derived from ICSI: a case report” J Ovarian Res (2025); Nov; 18:236

15. Liu, C.*, Zhang, H.*, Mao, J.*, Zhang, S.*, Tian, X., Zhu, Y., Wang, C., Fang, J., Pan, H., Kang, N., Zhang, Y., Zhou, J., Zhen, X., Guijun, Y., Li, C., Hu, Y., Ye, C., Xie, R., So, C.#, Sun, H.#, Ding, L#. “Mevalonate metabolites boost aged oocyte quality through prenylation of small GTPases” Nat Aging (2025); Oct; 5(10):2022-2038

14. Wang, J., So, C. “Aged eggs improve within young follicles” Nat Aging (2024); Oct; 4(10):1338-1339

13. Jentoft, I.M.A., Bäuerlein, F.J.B., Welp, L.M., Cooper, B.H., Petrovic, A., So, C., Penir, S.M., Politi, A.Z., Horokhovskyi, Y., Takala, I., Eckel, H., Moltrecht, R., Lénárt, P., Cavazza, T., Liepe, J., Brose, N., Urlaub, H., Fernández-Busnadiego, R., Schuh, M. “Mammalian oocytes store proteins for the early embryo on cytoplasmic lattices” 球友(中国)qy (2023); Nov; 186(24):5308-5327.e25

12. Sigmund, F., Berezin, O., Beliakova, S., Magerl, B., Drawitsh, M., Piovesan, A., Gonçalves, F., Bodea, S-V., Winkler, S., Bousraou, Z., Grosshauser, M., Samara, E., Pujol-Martí, J., Schädler, S., So, C., Irsen, S., Walch, A., Kofler, F., Piraud, M., Kornfeld, J., Briggman, K., Westmeyer, G.G. “Genetically encoded barcodes for correlative volume electron microscopy” Nat Biotechnol. (2023); Apr; doi: 10.1038/s41587-023-01713-y

11. Cheng, S.*, Altmeppen, G.*, So, C., Welp, L.M., Penir, S., Ruhwedel, T., Menelaou, K., Harasimov, K., Stützer, A., Blayney, M., Elder, K., Möbius, W., Urlaub, H., Schuh, M. “Mammalian oocytes store 球友(中国)qys in a mitochondria-associated membraneless compartment” Science (2022); Oct; 378(6617):eabq4835

10. So, C., Menelaou, K., Uraji, J., Harasimov, K., Steyer, A.M., Seres, K.B., Bucevičius, J., Lukinavičius, G., Möbius, W., Sibold, C., Tandler-Schneider, A., Eckel, H., Moltrecht, R., Blayney, M., Elder, K., Schuh, M. “Mechanism of spindle pole organization and instability in human oocytes” Science (2022); Feb; 375(6581):eabj3944

- Covered by Nat. 球友(中国)qy Biol. in “Spindle instability in human oocytes”

- Highlighted by J. Assist. Reprod. Genet. in “Failure to focus seems to be a hominid thing”

9. So, C.*, Cheng, S.*, Schuh, M. “Phase separation during germline development” Trends 球友(中国)qy Biol. (2021); Apr; 31(4):254-268

8. Chan, Y.W.*, So, C.*, Yau, K.L., Chiu, K.C., Wang, X., Chan, F.L., Tsang, S.Y. “Adipose-derived stem 球友(中国)qys and cancer 球友(中国)qys fuse to generate cancer stem 球友(中国)qy-like 球友(中国)qys with increased tumorigenicity” J. 球友(中国)qy Physiol. (2020); Oct; 235(10):6794-6807

7. So, C.*, Seres, K.B.*, Steyer, A.M., Mönnich, E., Clift, D., Pejkovska, A., Möbius, W., Schuh, M. “A liquid-like spindle domain promotes acentrosomal spindle assembly in mammalian oocytes” Science (2019); Jun; 364(6447):eaat9557

- Recommended by F1000Prime

- Highlighted by J. Assist. Reprod. Genet. in “Phase transitions in human ARTs: fertility preservation comes of age”

6. Xu, Y., So, C., Lam, H.M., Fung, M.C., Tsang, S.Y. “Flow cytometric detection of newly-formed breast cancer stem 球友(中国)qy-like 球友(中国)qys after apoptosis reversal” J. Vis. Exp. (2019); Jan; (143)

5. Clift, D.*, So, C.*, McEwan, W.A., James, L.C., Schuh, M. “Acute and rapid degradation of endogenous proteins by Trim-Away” Nat. Protoc. (2018); Oct; 13(10):2149-2175

4. Xu, Y., So, C., Lam, H.M., Fung, M.C., Tsang, S.Y. “Apoptosis reversal promotes cancer stem 球友(中国)qy-like 球友(中国)qy formation” Neoplasia (2018); Mar; 20(3):295-303

3. Yang, H., Buisson, S., Bossi, G., Wallace, Z., Hancock, G., So, C., Asfield, R., Vuidepot, A., Mahon, T., Molloy, P., Oates, J., Paston, S.J., Aleksic, M., Hassan, N.J., Jakobsen, B.K., Dorrell, L. “Elimination of latently HIV-infected 球友(中国)qys from antiretroviral therapy-suppressed subjects by engineered immune-mobilizing T-球友(中国)qy receptors” Mol. Ther. (2016); Nov; 24(11):1913-1925

2. Lo, I.C., Chan, H.C., Qi, Z., Ng, K.L., So, C., Tsang, S.Y. “TRPV3 channel negatively regulates 球友(中国)qy cycle progression and safeguards the pluripotency of embryonic stem 球友(中国)qys” J. 球友(中国)qy Physiol. (2016); Feb; 231(2):403-413

1. Qi, Y., Qi, Z., Li, Z., Wong, C.K., So, C., Lo, I.C., Huang, Y., Yao, X., Tsang, S.Y. “Role of TRPV1 in the differentiation of mouse embryonic stem 球友(中国)qys into cardiomyocytes” PLoS One (2015); Jul; 10(7):e0133211