Extracellular chromatin as a non-cell-autonomous regulator of cell fate transitions

Host: Yogesh Kulathu

Venue: Small Lecture Theatre, Medical Sciences Institute, SLS

Abstract:

The reprogramming of somatic cells to an induced pluripotent stem (iPS) cell state requires profound signalling, transcriptional and epigenetic rewiring. Similarly, the regeneration of mammalian tissues involves significant changes in cell behaviour and the transient acquisition of functions mediate the repair of damage. These changes can be thought of as adaptive cell reprogramming. We previously demonstrated that protein citrullination is induced upon the introduction of the Yamanaka transcription factors into somatic cells, where it precedes and mediates their reprogramming. We have since found that the induction of citrullination is a general, evolutionarily conserved feature of tissue regeneration. The cells that activate citrullination are mutually exclusive with the iPS or tissue stem cells, suggesting that they act as “active bystanders” that mediate reprogramming in a non-cell-autonomous manner. Our findings open a new research avenue into the study of citrullination and extracellular chromatin as cell communication mechanisms that mediate cell fate transitions.

Bio:

Maria Christophorou is a Principal Investigator in Epigenetics at the Babraham Institute in Cambridge, UK. Her lab studies biochemical mechanisms that modulate the function of epigenetic regulators, focussing primarily on protein citrullination. She studied Biology at MIT as a Fulbright Scholar and completed a PhD at UCSF, where she studied mechanisms of p53-mediated tumour suppression. As a postdoc she was funded by EMBO and Human Frontier postdoctoral fellowships and focussed on chromatin biology. Working at The Gurdon Institute, Cambridge University, she discovered that the citrullinating enzyme peptidylarginine deiminase (PADI4) regulates pluripotency and described a molecular mechanism via which PADI4 mediates chromatin decondensation. She started an independent group as a Wellcome Trust and Royal Society Sir Henry Dale Fellow and Wellcome-Beit Fellow at the University of Edinburgh, before moving to Babraham Institute in 2020. Maria is passionate about bringing the citrullination research community together. She organised the first international conference on citrullination in 2022 and co-organised an EMBO Workshop in 2024.