Publications

I'm proud to share that our modeling of YY1 haploinsufficiency has just been published! https://www.nature.com/articles/s41380-025-02929-x 

Using organoids and neurons, we discovered that YY1 mutations affect the cross-talk between cells and also cause a non-cell autonomous phenotype in a cell-type-specific manner. Kudos to Marlene F Pereira and Veronica Finazzi, who led the experimental and computational part, and Alessandro Vitriolo and Giuseppe Testa, with whom we shared the supervision! A special thanks goes to the families of individuals affected by Gabriele de-Vries syndrome who provided samples to generate iPSCs Here a summary of the most important discoveries:

• YY1 mutations alter cross-talk between cells and cause also a non-cell autonomous phenotype! Among this, we found that healthy co-cultured astrocytes show signs of gliosis

• Cortical organoids recapitulated clinical features

• We identified a gene regulatory network disrupted in GADEVS samples, that involve 6 main transcription factors ( NEUROG2,  MXI1, HOXA5, EGR1, EBF3 and ETV5) whose cross-talk is disrupted in GADEVS

• YY1 does not affect all cells equally but progenitors are more vulnerable to its haploinsufficiency, opening new interpretation to YY1 role in establishing new cell identity

• Finally, a calltoaction for clinicians: please when you identify a new individual with YY1 mutations add it to our database: https://lnkd.in/edWyt5qE this is crucial to creating a network, follow-up, a better understanding of the clinical features, and increasing awareness!

In this multidisciplinary study, published in Science, we discovered that the fully looped state of CTCF-CTCF loops, created by Cohesin loop extrusion and responsible for the topologically associating domains, is rare and short-lived. This paper has become a landmark paper in the 3D genome and chromatin fields both for the biological relevance and the multidisciplinary approach we adopted. 

We discovered that YY1 haploinsufficiency causes an intellectual disability syndrome that had been undiagnosed until then. The scientific community recognizes this disease as Gabriele-de Vries syndrome (MIM #617557). This work was crucial for these patients since now that can be followed under a specific disease. Also, this work allows us to be a point of reference for patients, facilitate connection between families, clinicians, and scientists, and begin to provide better care.