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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/228929
Ver los metadatos del registro completo
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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 Técnicas2025-09-29T09:36:27Zoai: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:34982025-09-29 09:36:28.05CONICET 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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1844613143693623296 |
score |
13.070432 |