Neuronal actin cytoskeleton gain of function in the human brain

Autores
Szigeti, Kinga; Ihnatovych, Ivanna; Rosas, Nicolás Matías; Dorn, Ryu P.; Notari, Emily; Cortes Gomez, Eduardo; He, Muye; Maly, Ivan; Prasad, Shreyas; Nimmer, Erik; Heo, Yuna; Fuchsova, Beata; Bennett, David A.; Hofmann, Wilma A.; Pralle, Arnd; Bae, Yongho; Wang, Jianmin
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: While advancements in imaging techniques have led to major strides in deciphering the human brain, successful interventions are elusive and represent some of the most persistent translational gaps in medicine. Human restricted CHRFAM7A has been associated with neuropsychiatric disorders. Methods: The physiological role of CHRFAM7A in human brain is explored using multiomics approach on 600 post mortem human brain tissue samples. The emerging pathways and mechanistic hypotheses are tested and validated in an isogenic hiPSC model of CHRFAM7A knock-in medial ganglionic eminence progenitors and neurons. Findings: CHRFAM7A is identified as a modulator of intracellular calcium dynamics and an upstream regulator of Rac1. Rac1 activation re-designs the actin cytoskeleton leading to dynamic actin driven remodeling of membrane protrusion and a switch from filopodia to lamellipodia. The reinforced cytoskeleton leads to an advantage to tolerate stiffer mechanical properties of the extracellular environment. Interpretation: CHRFAM7A modifies the actin cytoskeleton to a more dynamic and stiffness resistant state in an α7nAChR dependent manner. CHRFAM7A may facilitate neuronal adaptation to changes in the brain environment in physiological and pathological conditions contributing to risk or recovery. Understanding how CHRFAM7A affects human brain requires human studies in the areas of memory formation and erasure, cognitive reserve, and neuronal plasticity. Funding: This work is supported in part by the Community Foundation for Greater Buffalo (Kinga Szigeti). Also, in part by the International Society for Neurochemistry (ISN) and The Company of Biologists (Nicolas Rosas). ROSMAP is supported by NIA grants P30AG10161, P30AG72975, R01AG15819, R01AG17917. U01AG46152, and U01AG61356.
Fil: Szigeti, Kinga. State University of New York; Estados Unidos
Fil: Ihnatovych, Ivanna. State University of New York; Estados Unidos
Fil: Rosas, Nicolás Matías. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina. State University of New York; Estados Unidos
Fil: Dorn, Ryu P.. State University of New York; Estados Unidos
Fil: Notari, Emily. State University of New York; Estados Unidos
Fil: Cortes Gomez, Eduardo. Roswell Park Comprehensive Cancer Center; Estados Unidos
Fil: He, Muye. State University of New York; Estados Unidos
Fil: Maly, Ivan. State University of New York; Estados Unidos
Fil: Prasad, Shreyas. State University of New York; Estados Unidos
Fil: Nimmer, Erik. State University of New York; Estados Unidos
Fil: Heo, Yuna. State University of New York; Estados Unidos
Fil: Fuchsova, Beata. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Bennett, David A.. Rush University Medical Center (rumc);
Fil: Hofmann, Wilma A.. State University of New York; Estados Unidos
Fil: Pralle, Arnd. State University of New York; Estados Unidos
Fil: Bae, Yongho. State University of New York; Estados Unidos
Fil: Wang, Jianmin. Roswell Park Comprehensive Cancer Center; Estados Unidos
Materia
ACTIN CYTOSKELETON
CHRFAM7A
HUMAN BRAIN
IPSC
MULTIOMICS ANALYSIS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/228929
Acceder
id CONICETDig_13dfd470776c106184c16267d2cc2ed0
oai_identifier_str oai:ri.conicet.gov.ar:11336/228929
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Neuronal actin cytoskeleton gain of function in the human brainSzigeti, KingaIhnatovych, IvannaRosas, Nicolás MatíasDorn, Ryu P.Notari, EmilyCortes Gomez, EduardoHe, MuyeMaly, IvanPrasad, ShreyasNimmer, ErikHeo, YunaFuchsova, BeataBennett, David A.Hofmann, Wilma A.Pralle, ArndBae, YonghoWang, JianminACTIN CYTOSKELETONCHRFAM7AHUMAN BRAINIPSCMULTIOMICS ANALYSIShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Background: While advancements in imaging techniques have led to major strides in deciphering the human brain, successful interventions are elusive and represent some of the most persistent translational gaps in medicine. Human restricted CHRFAM7A has been associated with neuropsychiatric disorders. Methods: The physiological role of CHRFAM7A in human brain is explored using multiomics approach on 600 post mortem human brain tissue samples. The emerging pathways and mechanistic hypotheses are tested and validated in an isogenic hiPSC model of CHRFAM7A knock-in medial ganglionic eminence progenitors and neurons. Findings: CHRFAM7A is identified as a modulator of intracellular calcium dynamics and an upstream regulator of Rac1. Rac1 activation re-designs the actin cytoskeleton leading to dynamic actin driven remodeling of membrane protrusion and a switch from filopodia to lamellipodia. The reinforced cytoskeleton leads to an advantage to tolerate stiffer mechanical properties of the extracellular environment. Interpretation: CHRFAM7A modifies the actin cytoskeleton to a more dynamic and stiffness resistant state in an α7nAChR dependent manner. CHRFAM7A may facilitate neuronal adaptation to changes in the brain environment in physiological and pathological conditions contributing to risk or recovery. Understanding how CHRFAM7A affects human brain requires human studies in the areas of memory formation and erasure, cognitive reserve, and neuronal plasticity. Funding: This work is supported in part by the Community Foundation for Greater Buffalo (Kinga Szigeti). Also, in part by the International Society for Neurochemistry (ISN) and The Company of Biologists (Nicolas Rosas). ROSMAP is supported by NIA grants P30AG10161, P30AG72975, R01AG15819, R01AG17917. U01AG46152, and U01AG61356.Fil: Szigeti, Kinga. State University of New York; Estados UnidosFil: Ihnatovych, Ivanna. State University of New York; Estados UnidosFil: Rosas, Nicolás Matías. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina. State University of New York; Estados UnidosFil: Dorn, Ryu P.. State University of New York; Estados UnidosFil: Notari, Emily. State University of New York; Estados UnidosFil: Cortes Gomez, Eduardo. Roswell Park Comprehensive Cancer Center; Estados UnidosFil: He, Muye. State University of New York; Estados UnidosFil: Maly, Ivan. State University of New York; Estados UnidosFil: Prasad, Shreyas. State University of New York; Estados UnidosFil: Nimmer, Erik. State University of New York; Estados UnidosFil: Heo, Yuna. State University of New York; Estados UnidosFil: Fuchsova, Beata. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Bennett, David A.. Rush University Medical Center (rumc);Fil: Hofmann, Wilma A.. State University of New York; Estados UnidosFil: Pralle, Arnd. State University of New York; Estados UnidosFil: Bae, Yongho. State University of New York; Estados UnidosFil: Wang, Jianmin. Roswell Park Comprehensive Cancer Center; Estados UnidosElsevier2023-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/228929Szigeti, Kinga; Ihnatovych, Ivanna; Rosas, Nicolás Matías; Dorn, Ryu P.; Notari, Emily; et al.; Neuronal actin cytoskeleton gain of function in the human brain; Elsevier; eBioMedicine; 95; 104725; 9-2023; 1-152352-3964CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ebiom.2023.104725info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2352396423002906info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:04:34Zoai:ri.conicet.gov.ar:11336/228929instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:04:34.289CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Neuronal actin cytoskeleton gain of function in the human brain
title Neuronal actin cytoskeleton gain of function in the human brain
spellingShingle Neuronal actin cytoskeleton gain of function in the human brain
Szigeti, Kinga
ACTIN CYTOSKELETON
CHRFAM7A
HUMAN BRAIN
IPSC
MULTIOMICS ANALYSIS
title_short Neuronal actin cytoskeleton gain of function in the human brain
title_full Neuronal actin cytoskeleton gain of function in the human brain
title_fullStr Neuronal actin cytoskeleton gain of function in the human brain
title_full_unstemmed Neuronal actin cytoskeleton gain of function in the human brain
title_sort Neuronal actin cytoskeleton gain of function in the human brain
dc.creator.none.fl_str_mv Szigeti, Kinga
Ihnatovych, Ivanna
Rosas, Nicolás Matías
Dorn, Ryu P.
Notari, Emily
Cortes Gomez, Eduardo
He, Muye
Maly, Ivan
Prasad, Shreyas
Nimmer, Erik
Heo, Yuna
Fuchsova, Beata
Bennett, David A.
Hofmann, Wilma A.
Pralle, Arnd
Bae, Yongho
Wang, Jianmin
author Szigeti, Kinga
author_facet Szigeti, Kinga
Ihnatovych, Ivanna
Rosas, Nicolás Matías
Dorn, Ryu P.
Notari, Emily
Cortes Gomez, Eduardo
He, Muye
Maly, Ivan
Prasad, Shreyas
Nimmer, Erik
Heo, Yuna
Fuchsova, Beata
Bennett, David A.
Hofmann, Wilma A.
Pralle, Arnd
Bae, Yongho
Wang, Jianmin
author_role author
author2 Ihnatovych, Ivanna
Rosas, Nicolás Matías
Dorn, Ryu P.
Notari, Emily
Cortes Gomez, Eduardo
He, Muye
Maly, Ivan
Prasad, Shreyas
Nimmer, Erik
Heo, Yuna
Fuchsova, Beata
Bennett, David A.
Hofmann, Wilma A.
Pralle, Arnd
Bae, Yongho
Wang, Jianmin
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ACTIN CYTOSKELETON
CHRFAM7A
HUMAN BRAIN
IPSC
MULTIOMICS ANALYSIS
topic ACTIN CYTOSKELETON
CHRFAM7A
HUMAN BRAIN
IPSC
MULTIOMICS ANALYSIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Background: While advancements in imaging techniques have led to major strides in deciphering the human brain, successful interventions are elusive and represent some of the most persistent translational gaps in medicine. Human restricted CHRFAM7A has been associated with neuropsychiatric disorders. Methods: The physiological role of CHRFAM7A in human brain is explored using multiomics approach on 600 post mortem human brain tissue samples. The emerging pathways and mechanistic hypotheses are tested and validated in an isogenic hiPSC model of CHRFAM7A knock-in medial ganglionic eminence progenitors and neurons. Findings: CHRFAM7A is identified as a modulator of intracellular calcium dynamics and an upstream regulator of Rac1. Rac1 activation re-designs the actin cytoskeleton leading to dynamic actin driven remodeling of membrane protrusion and a switch from filopodia to lamellipodia. The reinforced cytoskeleton leads to an advantage to tolerate stiffer mechanical properties of the extracellular environment. Interpretation: CHRFAM7A modifies the actin cytoskeleton to a more dynamic and stiffness resistant state in an α7nAChR dependent manner. CHRFAM7A may facilitate neuronal adaptation to changes in the brain environment in physiological and pathological conditions contributing to risk or recovery. Understanding how CHRFAM7A affects human brain requires human studies in the areas of memory formation and erasure, cognitive reserve, and neuronal plasticity. Funding: This work is supported in part by the Community Foundation for Greater Buffalo (Kinga Szigeti). Also, in part by the International Society for Neurochemistry (ISN) and The Company of Biologists (Nicolas Rosas). ROSMAP is supported by NIA grants P30AG10161, P30AG72975, R01AG15819, R01AG17917. U01AG46152, and U01AG61356.
Fil: Szigeti, Kinga. State University of New York; Estados Unidos
Fil: Ihnatovych, Ivanna. State University of New York; Estados Unidos
Fil: Rosas, Nicolás Matías. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina. State University of New York; Estados Unidos
Fil: Dorn, Ryu P.. State University of New York; Estados Unidos
Fil: Notari, Emily. State University of New York; Estados Unidos
Fil: Cortes Gomez, Eduardo. Roswell Park Comprehensive Cancer Center; Estados Unidos
Fil: He, Muye. State University of New York; Estados Unidos
Fil: Maly, Ivan. State University of New York; Estados Unidos
Fil: Prasad, Shreyas. State University of New York; Estados Unidos
Fil: Nimmer, Erik. State University of New York; Estados Unidos
Fil: Heo, Yuna. State University of New York; Estados Unidos
Fil: Fuchsova, Beata. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Bennett, David A.. Rush University Medical Center (rumc);
Fil: Hofmann, Wilma A.. State University of New York; Estados Unidos
Fil: Pralle, Arnd. State University of New York; Estados Unidos
Fil: Bae, Yongho. State University of New York; Estados Unidos
Fil: Wang, Jianmin. Roswell Park Comprehensive Cancer Center; Estados Unidos
description Background: While advancements in imaging techniques have led to major strides in deciphering the human brain, successful interventions are elusive and represent some of the most persistent translational gaps in medicine. Human restricted CHRFAM7A has been associated with neuropsychiatric disorders. Methods: The physiological role of CHRFAM7A in human brain is explored using multiomics approach on 600 post mortem human brain tissue samples. The emerging pathways and mechanistic hypotheses are tested and validated in an isogenic hiPSC model of CHRFAM7A knock-in medial ganglionic eminence progenitors and neurons. Findings: CHRFAM7A is identified as a modulator of intracellular calcium dynamics and an upstream regulator of Rac1. Rac1 activation re-designs the actin cytoskeleton leading to dynamic actin driven remodeling of membrane protrusion and a switch from filopodia to lamellipodia. The reinforced cytoskeleton leads to an advantage to tolerate stiffer mechanical properties of the extracellular environment. Interpretation: CHRFAM7A modifies the actin cytoskeleton to a more dynamic and stiffness resistant state in an α7nAChR dependent manner. CHRFAM7A may facilitate neuronal adaptation to changes in the brain environment in physiological and pathological conditions contributing to risk or recovery. Understanding how CHRFAM7A affects human brain requires human studies in the areas of memory formation and erasure, cognitive reserve, and neuronal plasticity. Funding: This work is supported in part by the Community Foundation for Greater Buffalo (Kinga Szigeti). Also, in part by the International Society for Neurochemistry (ISN) and The Company of Biologists (Nicolas Rosas). ROSMAP is supported by NIA grants P30AG10161, P30AG72975, R01AG15819, R01AG17917. U01AG46152, and U01AG61356.
publishDate 2023
dc.date.none.fl_str_mv 2023-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/228929
Szigeti, Kinga; Ihnatovych, Ivanna; Rosas, Nicolás Matías; Dorn, Ryu P.; Notari, Emily; et al.; Neuronal actin cytoskeleton gain of function in the human brain; Elsevier; eBioMedicine; 95; 104725; 9-2023; 1-15
2352-3964
CONICET Digital
CONICET
url http://hdl.handle.net/11336/228929
identifier_str_mv Szigeti, Kinga; Ihnatovych, Ivanna; Rosas, Nicolás Matías; Dorn, Ryu P.; Notari, Emily; et al.; Neuronal actin cytoskeleton gain of function in the human brain; Elsevier; eBioMedicine; 95; 104725; 9-2023; 1-15
2352-3964
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ebiom.2023.104725
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2352396423002906
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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