In this episode of the Epigenetics Podcast, we talked with Vincent Pasque from KU Leuven about his work on the reprogramming of cell identity through epigenetic mechanisms, particularly during early development and cellular reprogramming.

We begin by tracing Vincent's journey into biology, sparked by early childhood experiences in nature and meaningful encounters with inspiring teachers. His fascination with the complexities of biology crystallized during a pivotal moment while listening to a radio segment on epigenetics in the late '90s, which led him to pursue studies in genetics and biochemistry. This formative path brought him to leading institutions, including the prestigious lab of John Gurdon, where he explored the phenomenon of nuclear reprogramming. Vincent recounts his early experiments that led to the discovery of macro H2A as a barrier to reprogramming, emphasizing the core challenge of erasing somatic cell identity.

As the conversation unfolds, Vincent introduces us to critical findings from his research. He shares how the inactive X chromosome serves as a compelling model to investigate epigenetic regulation, revealing that the dynamics of reprogramming and differentiation are far from simple reversals of development. He highlights the significant differences between male and female iPSCs and how X-linked genes influence DNA methylation and differentiation rates in these cells. The implications of these findings extend beyond developmental biology to inform our understanding of diseases, particularly cancer.

Transitioning to his current work, Vincent describes pioneering advances in characterizing the chromatin-associated proteome during the differentiation of human pluripotent stem cells. The surprising discovery of elevated histone modifications in naïve cells leads to intriguing questions about the barriers to cellular plasticity and the mechanisms by which cells resist alternative fate conversions. The potential applications of this research could reshape our approach to regenerative medicine and therapeutic interventions.

Pasque V, Gillich A, Garrett N, Gurdon JB. Histone variant macroH2A confers resistance to nuclear reprogramming. The EMBO Journal. 2011 May;30(12):2373-2387. DOI: 10.1038/emboj.2011.144. PMID: 21552206; PMCID: PMC3116279.

Jullien, J., Miyamoto, K., Pasque, V., Allen, G. E., Bradshaw, C. R., Garrett, N. J., Halley-Stott, R. P., Kimura, H., Ohsumi, K., & Gurdon, J. B. (2014). Hierarchical Molecular Events Driven by Oocyte-Specific Factors Lead to Rapid and Extensive Reprogramming. Molecular Cell, 55(4), 524–536. https://doi.org/10.1016/j.molcel.2014.06.024

Pasque V, Tchieu J, Karnik R, et al. X chromosome reactivation dynamics reveal stages of reprogramming to pluripotency. Cell. 2014 Dec;159(7):1681-1697. DOI: 10.1016/j.cell.2014.11.040. PMID: 25525883; PMCID: PMC4282187.

Zijlmans DW, Talon I, Verhelst S, et al. Integrated multi-omics reveal polycomb repressive complex 2 restricts human trophoblast induction. Nature Cell Biology. 2022 Jun;24(6):858-871. DOI: 10.1038/s41556-022-00932-w. PMID: 35697783; PMCID: PMC9203278.

The Discovery of Genomic Imprinting (Azim Surani)

Gene Expression Control and Intricacies of X-chromosome Inactivation (Claire Rougeulle)

Epigenetics and X-Inactivation (Edith Heard)

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