Dottoressa di ricerca

ciclo: XXXIII


Huntington's disease (HD) is a fully penetrant neurodegenerative disease caused by a dominantly inherited CAG trinucleotide repeat expansion in the huntingtin gene on chromosome 4. It is characterized by cognitive, motor and psychiatric disturbance. A rare juvenile form has onset in childhood or adolescence. The evolution of disease is insidious and structural and functional brain changes may be present more than a decade before symptoms and signs become manifest. The earliest site of pathology is the striatum. The pharmacological treatments in Huntington's disease is currently limited because pathophysiological mechanisms at the base of onset are poorly understood. The primary objective of this PhD project was the creation of a model system for Huntington's disease through the production and characterization of iPSCs from HD patients We isolated fibroblasts from three HD patients with different number of CAG repeats, in order to generate IPSc. After a neuralization protocol was performed on iPSCs from both two healthy donors and three HD patient, respectively with 43,64, 85 CAG repeats. In our lab, a reproducible system to establish stable hiNSCs, directly from iPSCs, able to spontaneously differentiate into the three neural lineages: astrocytes, oligodendrocytes and neurons, was optimized. The spontaneous differentiation, without the addition of molecules that induce neural commitment will permit us to study the contemporary development of all three neural lineages. Neurospheres obtained from HD patients immediately showed differences from healthy controls. They showed a higher rate of growth, a reduction in the expression of differentiation markers and an increase in pluripotency markers. These data have led us to hypothesize a greater self-renewal in HD neurospheres. We therefore decided to focus our attention on the balance between selfrenewal and differentiation, in particular on the role of histone methyltransferase Ezh2 in this regulation. From subsequent analyses it emerged that in HD neurospheres there is a significant increase in the Ezh2 protein, compared with the levels expressed in healthy controls. Preliminary data has led us to hypothesize that there is a direct relationship between increase in EZH2 protein and elongation of the polyQ tract in the Htt protein.

Produzione scientifica

11573/1665595 - 2023 - Generation of an induced pluripotent stem cell line CSSi015-A (9553), carrying a point mutation c.2915C > T in the human calcium sensing receptor (CasR) gene
Rotundo, Giovannina; Turco, Elisa Maria; Ruotolo, Giorgia; Torrente, Isabella; Candido, Ornella; Lopez, Gianluca; Ferrari, Daniela; Caputi, Caterina; Mastrangelo, Mario; Pisani, Francesco; Gelati, Maurizio; Guarnieri, Vito; Vescovi, Angelo Luigi; Rosati, Jessica - 01a Articolo in rivista
rivista: STEM CELL RESEARCH (Amsterdam : Elsevier) pp. 103023- - issn: 1876-7753 - wos: WOS:001010859600001 (1) - scopus: 2-s2.0-85146083988 (1)

11573/1184907 - 2018 - Generation of induced pluripotent stem cell line, CSSi004-A (2962), from a patient diagnosed with Huntington's disease at the presymptomatic stage
Bidollari, Eris; Rotundo, Giovannina; Ferrari, Daniela; Candido, Ornella; Bernardini, Laura; Consoli, Federica; De Luca, Alessandro; Santimone, Iolanda; Lamorte, Giuseppe; Ilari, Andrea; Squitieri, Ferdinando; Vescovi, Angelo Luigi; Rosati, Jessica - 01a Articolo in rivista
rivista: STEM CELL RESEARCH (Amsterdam : Elsevier) pp. 145-148 - issn: 1873-5061 - wos: WOS:000428799700026 (5) - scopus: 2-s2.0-85042460767 (6)

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