Tread -9- EpiSci - This is the result of a long journey and I have no words to express my gratitude to the people that started, joined and helped to finish this study. I am proud and honored to have had the opportunity to work with such amazing colleagues. So... Thanks to:

Tread -11- @akispapantonis.bsky.social @carstenschulte4.bsky.social

We hope that you will like our study! Reach me out for discussions and feedback!

Tread -10- EpiSci - @yomna96.bsky.social EiriniKalogerakou @matthiasakyel.bsky.social MargaritaDarna @priyakmr.bsky.social @simonstitzinger.bsky.social JannisGottwald KonstantinaKaplani ClaudioPiazzoni ManyuDu AndreasJanshoff @ibrahimcisse.bsky.social PaoloMilani @forna.bsky.social

Tread -8- EpiSci - We explicate how nanotopography-sensitive and mechanotransduction-dependent Nanog regulation is mediated by KDM3A These results show for the first time a molecular mechanism by which nanotopography-dependent stimulation specifically triggers a nuclear epigenetic mechanoresponse

Tread -7- EpiSci - 3. Nanotopography upregulates KDM3A,a specific Histone H3K9me2 demethylase. We discovered a new variant of KDM3A in mESCs. We developed a degron system which efficiently ablates all variants allowing to study the mechanistic role of the protein in an acute and reversible way.

Tread -6- EpiSci - RNA-seq analysis reveals that nanotopography induces a broad transcriptional response characterised by downregulation of integrin adhesion complexes, actin cytoskeleton organisation, and cell migration, alongside upregulation of core pluripotency factors such as Nanog.

Tread -5- Consistently with nuclear 3D changes, mESC/nanotopography interaction induces marked changes in chromatin organisation with reduced levels of H3K27me3 and H3K9me2, concomitant with increased H3K4me3. H3K9me3 levels remain unchanged, but is redistributed toward the nuclear periphery .

Tread -4- EpiSci - Our AFM measurements further reveal that nanotopography induces a progressive decrease in cellular tension and stiffness and importantly is accompanied by a change of the nuclear 3D shape.

Tread -3- EpiSci - We used nanofabrication technique Supersonic Cluster Beam Deposition (SCBD) to produce substrates with nanotopographical features of defined roughness that mimic ultrastructural ECM characteristics. Nanotopography strongly impact mESCs morphology.

Tread-2- EpiSci - The extracellular matrix (ECM) topography is increasingly recognised as a powerful regulator of cell behaviour, yet whether nanoscale topography can directly and deterministically instruct nuclear architecture and cell identity remains virtually unknown.

Tread -1- EpiSci - I am very proud to share with you our new study that you can access on @biorxivpreprint.bsky.social (see link below)
"The Interaction with Nanotopographical Environment regulates nuclear mechanoresponse in mESCs via Histone Demethylase KDM3A.
www.biorxiv.org/content/10.6...