Authors
Zachary Gardner, Ricardo Linares-Saldana, Krishna Kumar Haridhasapavalan, Pedro O Méndez Fernández, Vasia Barka, Rachel Yang, Bailey Koch-Bojalad, Arun Padmanabhan, Qiaohong Wang, Parisha P Shah, Son C Nguyen, Eric F Joyce, Rajan Jain
Published in
Science advances. Volume 12. Issue 33. Pages eaec3453. Aug 14, 2026. Epub Aug 14, 2026.
Abstract
Fibroblasts adopt diverse cell states in response to inductive cues to maintain tissue homeostasis. We leveraged this cell-state plasticity to define how genome organization contributes to changes in cellular identity. We show that TGF-β reconfigures topologically associating domains and chromatin loops at genes upregulated during fibroblast activation into myofibroblasts. Cohesin is required for gene induction during fibroblast activation, and enhanced cohesin stability is sufficient to bypass TGF-β signaling and drive a myofibroblast-like state. Emerging evidence suggests chromatin spatial positioning relative to nuclear speckles can regulate gene expression. Therefore, we examined the role of the critical nuclear speckle component SON and showed that it is required for myofibroblast gene expression. Notably, enhancing genome folding partially rescued gene expression in fibroblasts with SON-depleted nuclear speckles. Together, these findings advance our understanding of fibrosis and support a model in which distinct facets of genome organization converge to orchestrate cell-state transitions.
PMID:
42599997
Bibliographic data and abstract were imported from PubMed on 15 Aug 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 14
- Comments 0