In vitro-derived medium spiny neurons recapitulate human striatal development and complexity at single-cell resolution
Articolo
Data di Pubblicazione:
2022
Citazione:
In vitro-derived medium spiny neurons recapitulate human striatal development and complexity at single-cell resolution / P. Conforti, V.D. Bocchi, I. Campus, L. Scaramuzza, M. Galimberti, T. Lischetti, F. Talpo, M. Pedrazzoli, A. Murgia, I. Ferrari, C. Cordiglieri, A. Fasciani, E. Arenas, D. Felsenfeld, G. Biella, D. Besusso, E. Cattaneo. - In: CELL REPORTS. METHODS. - ISSN 2667-2375. - 2:12(2022 Dec 19), pp. 100367.1-100367.18. [10.1016/j.crmeth.2022.100367]
Abstract:
Stem cell engineering of striatal medium spiny neurons (MSNs) is a promising strategy to understand dis-
eases affecting the striatum and for cell-replacement therapies in different neurological diseases. Protocols
to generate cells from human pluripotent stem cells (PSCs) are scarce and how well they recapitulate the
endogenous fetal cells remains poorly understood. We have developed a protocol that modulates cell seed-
ing density and exposure to specific morphogens that generates authentic and functional D1- and D2-MSNs
with a high degree of reproducibility in 25 days of differentiation. Single-cell RNA sequencing (scRNA-seq)
shows that our cells can mimic the cell-fate acquisition steps observed in vivo in terms of cell type compo-
sition, gene expression, and signaling pathways. Finally, by modulating the midkine pathway we show that
we can increase the yield of MSNs. We expect that this protocol will help decode pathogenesis factors in
striatal diseases and eventually facilitate cell-replacement therapies for Huntington’s disease (HD).
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
P. Conforti, V.D. Bocchi, I. Campus, L. Scaramuzza, M. Galimberti, T. Lischetti, F. Talpo, M. Pedrazzoli, A. Murgia, I. Ferrari, C. Cordiglieri, A. Fasciani, E. Arenas, D. Felsenfeld, G. Biella, D. Besusso, E. Cattaneo
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