Cortical neurons obtained from patient-derived iPSCs with GNAO1 p.G203R variant show altered differentiation and functional properties

Maria Cristina Benedetti; Tiziano D'andrea; Alessio Colantoni; Denis Silachev; Valeria de Turris; Zaira Boussadia; Valentina A. Babenko; Egor A. Volovikov; Lilia Belikova; Alexandra N. Bogomazova; Rita Pepponi; Dosh Whye; Elizabeth D. Buttermore; Gian Gaetano Tartaglia; Maria A. Lagarkova; Vladimir L. Katanaev; Ilya Musayev; Simone Martinelli; Sergio Fucile; Alessandro Rosa

doi:10.1016/j.heliyon.2024.e26656

Cortical neurons obtained from patient-derived iPSCs with GNAO1 p.G203R variant show altered differentiation and functional properties

Maria Cristina Benedetti, Tiziano D'andrea, Alessio Colantoni, Denis Silachev, Valeria de Turris, Zaira Boussadia, Valentina A. Babenko, Egor A. Volovikov, Lilia Belikova, Alexandra N. Bogomazova, Rita Pepponi, Dosh Whye, Elizabeth D. Buttermore, Gian Gaetano Tartaglia, Maria A. Lagarkova, Vladimir L. Katanaev, Ilya Musayev, Simone Martinelli, Sergio Fucile, Alessandro Rosa^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

Abstract

Pathogenic variants in the GNAO1 gene, encoding the alpha subunit of an inhibitory heterotrimeric guanine nucleotide-binding protein (Go) highly expressed in the mammalian brain, have been linked to encephalopathy characterized by different combinations of neurological symptoms, including developmental delay, hypotonia, epilepsy and hyperkinetic movement disorder with life-threatening paroxysmal exacerbations. Currently, there are only symptomatic treatments, and little is known about the pathophysiology of GNAO1-related disorders. Here, we report the characterization of a new in vitro model system based on patient-derived induced pluripotent stem cells (hiPSCs) carrying the recurrent p.G203R amino acid substitution in G alpha o, and a CRISPR-Cas9-genetically corrected isogenic control line. RNA-Seq analysis highlighted aberrant cell fate commitment in neuronal progenitor cells carrying the p.G203R pathogenic

Original language	English
Article number	e26656
Number of pages	17
Journal	Heliyon
Volume	10
Issue number	5
DOIs	https://doi.org/10.1016/j.heliyon.2024.e26656
Publication status	Published - 15 Mar 2024
Externally published	Yes

Keywords

Encephalopathy
Gnao1
Induced pluripotent stem cell
Movement disorder
Neural rosette
Wnt

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10.1016/j.heliyon.2024.e26656

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Benedetti, M. C., D'andrea, T., Colantoni, A., Silachev, D., de Turris, V., Boussadia, Z., Babenko, V. A., Volovikov, E. A., Belikova, L., Bogomazova, A. N., Pepponi, R., Whye, D., Buttermore, E. D., Tartaglia, G. G., Lagarkova, M. A., Katanaev, V. L., Musayev, I., Martinelli, S., Fucile, S., & Rosa, A. (2024). Cortical neurons obtained from patient-derived iPSCs with GNAO1 p.G203R variant show altered differentiation and functional properties. Heliyon, 10(5), Article e26656. https://doi.org/10.1016/j.heliyon.2024.e26656

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title = "Cortical neurons obtained from patient-derived iPSCs with GNAO1 p.G203R variant show altered differentiation and functional properties",

abstract = "Pathogenic variants in the GNAO1 gene, encoding the alpha subunit of an inhibitory heterotrimeric guanine nucleotide-binding protein (Go) highly expressed in the mammalian brain, have been linked to encephalopathy characterized by different combinations of neurological symptoms, including developmental delay, hypotonia, epilepsy and hyperkinetic movement disorder with life-threatening paroxysmal exacerbations. Currently, there are only symptomatic treatments, and little is known about the pathophysiology of GNAO1-related disorders. Here, we report the characterization of a new in vitro model system based on patient-derived induced pluripotent stem cells (hiPSCs) carrying the recurrent p.G203R amino acid substitution in G alpha o, and a CRISPR-Cas9-genetically corrected isogenic control line. RNA-Seq analysis highlighted aberrant cell fate commitment in neuronal progenitor cells carrying the p.G203R pathogenic",

keywords = "Encephalopathy, Gnao1, Induced pluripotent stem cell, Movement disorder, Neural rosette, Wnt",

author = "Benedetti, {Maria Cristina} and Tiziano D'andrea and Alessio Colantoni and Denis Silachev and {de Turris}, Valeria and Zaira Boussadia and Babenko, {Valentina A.} and Volovikov, {Egor A.} and Lilia Belikova and Bogomazova, {Alexandra N.} and Rita Pepponi and Dosh Whye and Buttermore, {Elizabeth D.} and Tartaglia, {Gian Gaetano} and Lagarkova, {Maria A.} and Katanaev, {Vladimir L.} and Ilya Musayev and Simone Martinelli and Sergio Fucile and Alessandro Rosa",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

month = mar,

day = "15",

doi = "10.1016/j.heliyon.2024.e26656",

language = "English",

volume = "10",

journal = "Heliyon",

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Benedetti, MC, D'andrea, T, Colantoni, A, Silachev, D, de Turris, V, Boussadia, Z, Babenko, VA, Volovikov, EA, Belikova, L, Bogomazova, AN, Pepponi, R, Whye, D, Buttermore, ED, Tartaglia, GG, Lagarkova, MA, Katanaev, VL, Musayev, I, Martinelli, S, Fucile, S & Rosa, A 2024, 'Cortical neurons obtained from patient-derived iPSCs with GNAO1 p.G203R variant show altered differentiation and functional properties', Heliyon, vol. 10, no. 5, e26656. https://doi.org/10.1016/j.heliyon.2024.e26656

TY - JOUR

T1 - Cortical neurons obtained from patient-derived iPSCs with GNAO1 p.G203R variant show altered differentiation and functional properties

AU - Benedetti, Maria Cristina

AU - D'andrea, Tiziano

AU - Colantoni, Alessio

AU - Silachev, Denis

AU - de Turris, Valeria

AU - Boussadia, Zaira

AU - Babenko, Valentina A.

AU - Volovikov, Egor A.

AU - Belikova, Lilia

AU - Bogomazova, Alexandra N.

AU - Pepponi, Rita

AU - Whye, Dosh

AU - Buttermore, Elizabeth D.

AU - Tartaglia, Gian Gaetano

AU - Lagarkova, Maria A.

AU - Katanaev, Vladimir L.

AU - Musayev, Ilya

AU - Martinelli, Simone

AU - Fucile, Sergio

AU - Rosa, Alessandro

PY - 2024/3/15

Y1 - 2024/3/15

N2 - Pathogenic variants in the GNAO1 gene, encoding the alpha subunit of an inhibitory heterotrimeric guanine nucleotide-binding protein (Go) highly expressed in the mammalian brain, have been linked to encephalopathy characterized by different combinations of neurological symptoms, including developmental delay, hypotonia, epilepsy and hyperkinetic movement disorder with life-threatening paroxysmal exacerbations. Currently, there are only symptomatic treatments, and little is known about the pathophysiology of GNAO1-related disorders. Here, we report the characterization of a new in vitro model system based on patient-derived induced pluripotent stem cells (hiPSCs) carrying the recurrent p.G203R amino acid substitution in G alpha o, and a CRISPR-Cas9-genetically corrected isogenic control line. RNA-Seq analysis highlighted aberrant cell fate commitment in neuronal progenitor cells carrying the p.G203R pathogenic

AB - Pathogenic variants in the GNAO1 gene, encoding the alpha subunit of an inhibitory heterotrimeric guanine nucleotide-binding protein (Go) highly expressed in the mammalian brain, have been linked to encephalopathy characterized by different combinations of neurological symptoms, including developmental delay, hypotonia, epilepsy and hyperkinetic movement disorder with life-threatening paroxysmal exacerbations. Currently, there are only symptomatic treatments, and little is known about the pathophysiology of GNAO1-related disorders. Here, we report the characterization of a new in vitro model system based on patient-derived induced pluripotent stem cells (hiPSCs) carrying the recurrent p.G203R amino acid substitution in G alpha o, and a CRISPR-Cas9-genetically corrected isogenic control line. RNA-Seq analysis highlighted aberrant cell fate commitment in neuronal progenitor cells carrying the p.G203R pathogenic

KW - Encephalopathy

KW - Gnao1

KW - Induced pluripotent stem cell

KW - Movement disorder

KW - Neural rosette

KW - Wnt

UR - http://www.scopus.com/inward/record.url?scp=85186464713&partnerID=8YFLogxK

U2 - 10.1016/j.heliyon.2024.e26656

DO - 10.1016/j.heliyon.2024.e26656

M3 - Article

AN - SCOPUS:85186464713

SN - 2405-8440

VL - 10

JO - Heliyon

JF - Heliyon

IS - 5

M1 - e26656

ER -

Cortical neurons obtained from patient-derived iPSCs with GNAO1 p.G203R variant show altered differentiation and functional properties

Abstract

Keywords

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