Seminario: Dott.ssa Chiara Mozzetta – 24 Maggio 2022

Dott.ssa Chiara Mozzetta

Dott.ssa Chiara Mozzetta

Ricercatore CNR IBPM


Heterochromatin-nuclear lamina interactions regulate cell fate plasticity during skeletal muscle repair

24/05/2022 – ore 14:00


Cellular identity is specified by cell-specific transcription factors and maintained by epigenetic mechanisms. Beyond restricted activation of lineage-specific genes, alternative transcriptional programs must be repressed to specify a defined differentiation path. H3K9 methylation maintains cell identity orchestrating stable silencing and anchoring of alternate fate genes within the heterochromatic compartment underneath the nuclear lamina (NL). However, how this is achieved in a cell-specific manner is poorly understood. H3K9 methyltransferases (KMTs) are generally ubiquitously expressed and if, and how, they impede direct cell conversion in adult stem cells is still rather unexplored.
Here, we addressed this issue in a population of mesenchymal, multipotent, stromal cells, named Fibro-Adipogenic Progenitors (FAPs), whose developmental plasticity has been linked to skeletal muscle pathological phenotypes. We provide evidence of a druggable mechanism of heterochromatin perinuclear sequestration exploitable to reprogram FAPs in vivo. We show that pharmacological inhibition of H3K9 methylation can revert FAPs’ pathological fibro-adipogenic differentiation observed in diseased muscles, improving their regenerative capacity.