Cell Fate Dynamics 

Deciphering Cell Fate Decisions in multipotent lineages and their associated disorders 

Our lab investigates how genes that guide embryonic development are repurposed during disease initiation. We focus on neural crest cells (NCCs)—a highly plastic, multipotent population that gives rise to diverse cell types including melanocytes, craniofacial cartilage, and peripheral neurons. By studying how NCCs acquire and stabilize their fates during normal development, we aim to uncover how the same gene networks become dysregulated in diseases like melanoma and other neural crest associated disorders.

Melanocytes, which originate from neural crest cells, serve as a central model in our research. These pigment-producing cells are tightly regulated during embryogenesis, but their developmental plasticity also makes them susceptible to pathological reprogramming. Our work has revealed that genes crucial for melanocyte fate, such as mgat4b, are also involved in the early events of melanoma formation. These findings highlight a key theme of our research: developmental genes can be hijacked to initiate or promote disease.

To explore this intersection between development and pathology, we combine zebrafish and iPSC models with cutting-edge single-cell and genome-editing technologies. Using live imaging, CRISPR-based perturbations, and single-cell transcriptomics, we study how transcriptional and epigenetic programs evolve over time.

By dissecting how developmental gene circuits are reactivated in disease, we aim to uncover the fundamental principles of cell fate regulation. Our ultimate goal is to inform therapeutic strategies that target disease at its developmental root, offering new approaches for neural crest disorders.

Select Publications

• B. Sharma,K. Aswin,T. Jain,A. Nasreen,A. Aggarwal,Y.J. Subramaniam,J. Rengaraju,S.J. Agrawal,M. Bhatt,B. Paul,K. Chandrasekaran,A. Yadav,J. Soni,R. Ujjainiya,M.Q. Akhter,R. Pandey,S. Suresh,S. Sampathkumar, & V.T. Natarajan,  Mgat4b-mediated selective N-glycosylation regulates melanocyte development and melanoma progression, Proc. Natl. Acad. Sci. U.S.A. 122 (22) e2423831122, https://doi.org/10.1073/pnas.2423831122 (2025). 

• Distinct melanocyte subpopulations defined by stochastic expression of proliferation or maturation programs enable a rapid and sustainable pigmentation response. Ayush Aggarwal,Ayesha Nasreen,Babita Sharma,Sarthak Sahoo,Keerthic Aswin,Mohammed Faruq,Rajesh Pandey,Mohit K. Jolly,Abhyudai Singh,Rajesh S. Gokhale,Vivek T. Natarajan(2024). PLOS Biology 22(8): e3002776. https://doi.org/10.1371/journal.pbio.3002776 

• Ghazi M, Khanna S, Subramaniam Y, Rengaraju J, Sultan F, Gupta I, Sharma K, Chandna S, Gokhale RS, Natarajan VT. Sustained pigmentation causes DNA damage and invokes translesion polymerase Polκ for repair in melanocytes. Nucleic Acids Res. 2023 Oct 27;51(19):10451-10466 

• Raja, D.A., Subramaniam, Y.J., Aggarwal, A., Gotherwal, V., Babu, A., Tanwar, J., Motiani, R.K., Sivasubbu, S., Gokhale, R.S., Natarajan, V.T., 2020. Histone variant dictates fate biasing of neural crest cells to melanocyte lineage. Development.

• Raja, D.A., Gotherwal, V., Burse, S.A., Subramaniam, Y.J., Sultan, F., Vats, A., Gautam, H., Sharma, B., Sharma, S., Singh, A., Sivasubbu, S., Gokhale, R.S., Natarajan, V.T., 2020. pH‐controlled histone acetylation amplifies melanocyte differentiation downstream of MITF. EMBO Rep. 21.

• Grover, R., Burse, S.A., Shankrit, S., Aggarwal, A., Kirty, K., Narta, K., Srivastav, R., Ray, A.K., Malik, G., Vats, A., Motiani, R.K., Thukral, L., Roy, S.S., Bhattacharya, S., Sharma, R., Natarajan, K., Mukerji, M., Pandey, R., Gokhale, R.S., Natarajan, V.T., 2019. Myg1 exonuclease couples the nuclear and mitochondrial translational programs through RNA processing. Nucleic Acids Res. 47, 5852–5866.

• Vij M, Grover R, Gotherwal V, Wani NA, Joshi P, Gautam H, Sharma K, Chandna S, Gokhale RS, Rai R, Ganguli M, Natarajan VT., 2016. Bioinspired Functionalized Melanin Nanovariants with a Range of Properties Provide Effective Color Matched Photoprotection in Skin. Biomacromolecules. 12;17(9):2912-9.

• Gautam P, Chaurasia A, Bhattacharya A, Grover R; Indian Genome Variation Consortium, Mukerji M, Natarajan VT., 2015. Population diversity and adaptive evolution in keratinization genes: impact of environment in shaping skin phenotypes. Mol Biol Evol. 32(3):555-73.

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