Seminario Expansion of progenitor stem cells controls chromatin architecture to dictate cell fate decision
16 settembre 2026
Dr. Alberto Dinarello - Ricercatore Postdoc presso reNEW Center, Università di Copenaghen, Danimarca (ospite del Prof. N. Fachinello)
- 11:30 - 13:00
- Online su Microsoft Teams e in presenza : Aula Rossa, Igiene, Via San Giacomo 12, Bologna
- Salute, Scienza e tecnologia In inglese
Per partecipare
Ingresso libero
Programma
The ventral foregut is a proliferative region of the embryonic gut tube containing multipotent precursors of pancreas and liver. In vitro, ventral foregut stem cells organoids (VFG) can be generated from pluripotent stem cells and maintained in culture for several passages. VFG cultures proliferate and self-renew, gradually shortening cell cycle over passages. Although the morphology and the transcriptome of these cells do not change during expansion, we observed a marked alteration of chromatin landscape, with later cultures (more than passage 6) priming pancreatic- and hepatic-specific enhancers for later differentiation and decommissioning those associated with alternative lineage fate. Consistent with these changes, late VFG cultures differentiate more efficiently and produce better pancreatic endoderm then earlier passage cells (3 or less passages). The priming of enhancers regulating pancreatic differentiation correlates with an increased binding of FOXA1 and GATA6. In parallel, histone modifications associated with enhancer commissioning such as H3K27ac and H3K4me1 are progressively more abundant in the same regions. This suggests that time and/or proliferation are required to prepare enhancers for later activation through the gradual erasure of repressive chromatin. Taken together, our findings demonstrate that proliferation of intermediates in differentiation is not only about increasing cell number but is required to correctly configure chromatin at enhancers enabling efficient and effective differentiation.
Chi interverrà
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Alberto Dinarello
MSC Postdoc Fellow at reNEW Novo Nordisk Foundation Center, University of Copenhagen, Denmark
Alberto is a postdoctoral fellow in Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW) at University of Copenhagen, Denmark. His scientific interests focus on understanding how signaling pathways, transcription factors and chromatin remodeling cooperate to regulate cell fate decisions. He got his PhD in the laboratory of Professor Francesco Argenton, studying the canonical and non-canonical function of the transcription factor STAT3 in zebrafish and mouse embryonic stem cells. Afterwards, he joined the laboratory of Professor Charles Dinarello at Anschutz Medical Campus, University of Colorado, Denver (CO, USA) as a postdoc, studying the functions of IL-38 in gut homeostasis. For this project, he used murine intestinal organoids and identified the homeostatic roles of IL-38 and IL-1b for the maintenance of intestinal stem cells of the crypt. In 2023, he moved to Denmark to join the laboratory of Professor Joshua Brickman where he started his research on molecular mechanisms that determine proper cell fate decision during endoderm lineage specification. In particular, he is currently exploiting human ventral foregut stem cells generated from pluripotent stem cells to disentangle the role of chromatin remodeling and transcription factor binding in differentiation. He has recently been a visiting researcher in the lab of Eduard Stanley in Murdoch Children’s Research Institute, Melbourne (Australia) where he trained in advanced approaches for pancreatic and endocrine differentiation. Alberto’s scientific aim is to better understand the molecular mechanisms that govern stem cell differentiation and to apply the knowledge to improve cell replacement therapies for human diseases.
Contatti
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Nicola Facchinello