Suppressing aneuploidy-associated phenotypes improves the fitness of Trisomy 21 Cells

Autores
Hwang, Sunyoung; Williams, Jessica F.; Kneissig, Maja; Lioudyno, Maria; Rivera, Isabel; Helguera, Pablo Rodolfo; Busciglio, Jorge; Storchova, Zuzana; King, Megan C.; Torres, Martin Eduardo
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
An abnormal number of chromosomes, or aneuploidy, accounts for most spontaneous abortions, causes developmental defects, and is associated with aging and cancer. The molecular mechanisms by which aneuploidy disrupts cellular function remain largely unknown. Here, we show that aneuploidy disrupts the morphology of the nucleus. Mutations that increase the levels of long-chain bases suppress nuclear abnormalities of aneuploid yeast independent of karyotype identity. Quantitative lipidomics indicates that long-chain bases are integral components of the nuclear membrane in yeast. Cells isolated from patients with Down syndrome also show that abnormal nuclear morphologies and increases in long-chain bases not only suppress these abnormalities but also improve their fitness. We obtained similar results with cells isolated from patients with Patau or Edward syndrome, indicating that increases in long-chain bases improve the fitness of aneuploid cells in yeast and humans. Targeting lipid biosynthesis pathways represents an important strategy to suppress nuclear abnormalities in aneuploidy-associated diseases. The cellular defects associated with aneuploidy are not well defined. Hwang et al. show that aneuploid yeast and human cells have abnormal nuclear morphology. Targeting ceramide synthesis suppresses nuclear abnormalities and improves the proliferation of aneuploid cells, including cells isolated from patients with Down syndrome.
Fil: Hwang, Sunyoung. University Of Massachussets. Medical School; Estados Unidos
Fil: Williams, Jessica F.. University of Yale. School of Medicine; Estados Unidos
Fil: Kneissig, Maja. University of Kaiserslautern; Alemania
Fil: Lioudyno, Maria. University of California at Irvine; Estados Unidos
Fil: Rivera, Isabel. University of California at Irvine; Estados Unidos
Fil: Helguera, Pablo Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Busciglio, Jorge. University of California at Irvine; Estados Unidos
Fil: Storchova, Zuzana. University Of Kaiserlautern. Department Of Mathematics; Alemania
Fil: King, Megan C.. University of Yale. School of Medicine; Estados Unidos
Fil: Torres, Martin Eduardo. University Of Massachussets. Medical School; Estados Unidos
Materia
ANEUPLOIDY
DOWN SYNDROME
EDWARDS
LONG-CHAIN BASE
NUCLEAR ENVELOPE
NUCLEAR MORPHOLOGY
PATAU
SPHINGOLIPID
SPHINGOSINE
TRISOMY 21
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/128464
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/128464
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Suppressing aneuploidy-associated phenotypes improves the fitness of Trisomy 21 CellsHwang, SunyoungWilliams, Jessica F.Kneissig, MajaLioudyno, MariaRivera, IsabelHelguera, Pablo RodolfoBusciglio, JorgeStorchova, ZuzanaKing, Megan C.Torres, Martin EduardoANEUPLOIDYDOWN SYNDROMEEDWARDSLONG-CHAIN BASENUCLEAR ENVELOPENUCLEAR MORPHOLOGYPATAUSPHINGOLIPIDSPHINGOSINETRISOMY 21https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1An abnormal number of chromosomes, or aneuploidy, accounts for most spontaneous abortions, causes developmental defects, and is associated with aging and cancer. The molecular mechanisms by which aneuploidy disrupts cellular function remain largely unknown. Here, we show that aneuploidy disrupts the morphology of the nucleus. Mutations that increase the levels of long-chain bases suppress nuclear abnormalities of aneuploid yeast independent of karyotype identity. Quantitative lipidomics indicates that long-chain bases are integral components of the nuclear membrane in yeast. Cells isolated from patients with Down syndrome also show that abnormal nuclear morphologies and increases in long-chain bases not only suppress these abnormalities but also improve their fitness. We obtained similar results with cells isolated from patients with Patau or Edward syndrome, indicating that increases in long-chain bases improve the fitness of aneuploid cells in yeast and humans. Targeting lipid biosynthesis pathways represents an important strategy to suppress nuclear abnormalities in aneuploidy-associated diseases. The cellular defects associated with aneuploidy are not well defined. Hwang et al. show that aneuploid yeast and human cells have abnormal nuclear morphology. Targeting ceramide synthesis suppresses nuclear abnormalities and improves the proliferation of aneuploid cells, including cells isolated from patients with Down syndrome.Fil: Hwang, Sunyoung. University Of Massachussets. Medical School; Estados UnidosFil: Williams, Jessica F.. University of Yale. School of Medicine; Estados UnidosFil: Kneissig, Maja. University of Kaiserslautern; AlemaniaFil: Lioudyno, Maria. University of California at Irvine; Estados UnidosFil: Rivera, Isabel. University of California at Irvine; Estados UnidosFil: Helguera, Pablo Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Busciglio, Jorge. University of California at Irvine; Estados UnidosFil: Storchova, Zuzana. University Of Kaiserlautern. Department Of Mathematics; AlemaniaFil: King, Megan C.. University of Yale. School of Medicine; Estados UnidosFil: Torres, Martin Eduardo. University Of Massachussets. Medical School; Estados UnidosElsevier B.V.2019-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/128464Hwang, Sunyoung; Williams, Jessica F.; Kneissig, Maja; Lioudyno, Maria; Rivera, Isabel; et al.; Suppressing aneuploidy-associated phenotypes improves the fitness of Trisomy 21 Cells; Elsevier B.V.; Cell Reports; 29; 8; 11-2019; 2473-2488.e52211-1247CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S2211124719313737info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2019.10.059info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:55:08Zoai:ri.conicet.gov.ar:11336/128464instacron: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 09:55:09.177CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Suppressing aneuploidy-associated phenotypes improves the fitness of Trisomy 21 Cells
title Suppressing aneuploidy-associated phenotypes improves the fitness of Trisomy 21 Cells
spellingShingle Suppressing aneuploidy-associated phenotypes improves the fitness of Trisomy 21 Cells
Hwang, Sunyoung
ANEUPLOIDY
DOWN SYNDROME
EDWARDS
LONG-CHAIN BASE
NUCLEAR ENVELOPE
NUCLEAR MORPHOLOGY
PATAU
SPHINGOLIPID
SPHINGOSINE
TRISOMY 21
title_short Suppressing aneuploidy-associated phenotypes improves the fitness of Trisomy 21 Cells
title_full Suppressing aneuploidy-associated phenotypes improves the fitness of Trisomy 21 Cells
title_fullStr Suppressing aneuploidy-associated phenotypes improves the fitness of Trisomy 21 Cells
title_full_unstemmed Suppressing aneuploidy-associated phenotypes improves the fitness of Trisomy 21 Cells
title_sort Suppressing aneuploidy-associated phenotypes improves the fitness of Trisomy 21 Cells
dc.creator.none.fl_str_mv Hwang, Sunyoung
Williams, Jessica F.
Kneissig, Maja
Lioudyno, Maria
Rivera, Isabel
Helguera, Pablo Rodolfo
Busciglio, Jorge
Storchova, Zuzana
King, Megan C.
Torres, Martin Eduardo
author Hwang, Sunyoung
author_facet Hwang, Sunyoung
Williams, Jessica F.
Kneissig, Maja
Lioudyno, Maria
Rivera, Isabel
Helguera, Pablo Rodolfo
Busciglio, Jorge
Storchova, Zuzana
King, Megan C.
Torres, Martin Eduardo
author_role author
author2 Williams, Jessica F.
Kneissig, Maja
Lioudyno, Maria
Rivera, Isabel
Helguera, Pablo Rodolfo
Busciglio, Jorge
Storchova, Zuzana
King, Megan C.
Torres, Martin Eduardo
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ANEUPLOIDY
DOWN SYNDROME
EDWARDS
LONG-CHAIN BASE
NUCLEAR ENVELOPE
NUCLEAR MORPHOLOGY
PATAU
SPHINGOLIPID
SPHINGOSINE
TRISOMY 21
topic ANEUPLOIDY
DOWN SYNDROME
EDWARDS
LONG-CHAIN BASE
NUCLEAR ENVELOPE
NUCLEAR MORPHOLOGY
PATAU
SPHINGOLIPID
SPHINGOSINE
TRISOMY 21
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv An abnormal number of chromosomes, or aneuploidy, accounts for most spontaneous abortions, causes developmental defects, and is associated with aging and cancer. The molecular mechanisms by which aneuploidy disrupts cellular function remain largely unknown. Here, we show that aneuploidy disrupts the morphology of the nucleus. Mutations that increase the levels of long-chain bases suppress nuclear abnormalities of aneuploid yeast independent of karyotype identity. Quantitative lipidomics indicates that long-chain bases are integral components of the nuclear membrane in yeast. Cells isolated from patients with Down syndrome also show that abnormal nuclear morphologies and increases in long-chain bases not only suppress these abnormalities but also improve their fitness. We obtained similar results with cells isolated from patients with Patau or Edward syndrome, indicating that increases in long-chain bases improve the fitness of aneuploid cells in yeast and humans. Targeting lipid biosynthesis pathways represents an important strategy to suppress nuclear abnormalities in aneuploidy-associated diseases. The cellular defects associated with aneuploidy are not well defined. Hwang et al. show that aneuploid yeast and human cells have abnormal nuclear morphology. Targeting ceramide synthesis suppresses nuclear abnormalities and improves the proliferation of aneuploid cells, including cells isolated from patients with Down syndrome.
Fil: Hwang, Sunyoung. University Of Massachussets. Medical School; Estados Unidos
Fil: Williams, Jessica F.. University of Yale. School of Medicine; Estados Unidos
Fil: Kneissig, Maja. University of Kaiserslautern; Alemania
Fil: Lioudyno, Maria. University of California at Irvine; Estados Unidos
Fil: Rivera, Isabel. University of California at Irvine; Estados Unidos
Fil: Helguera, Pablo Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Busciglio, Jorge. University of California at Irvine; Estados Unidos
Fil: Storchova, Zuzana. University Of Kaiserlautern. Department Of Mathematics; Alemania
Fil: King, Megan C.. University of Yale. School of Medicine; Estados Unidos
Fil: Torres, Martin Eduardo. University Of Massachussets. Medical School; Estados Unidos
description An abnormal number of chromosomes, or aneuploidy, accounts for most spontaneous abortions, causes developmental defects, and is associated with aging and cancer. The molecular mechanisms by which aneuploidy disrupts cellular function remain largely unknown. Here, we show that aneuploidy disrupts the morphology of the nucleus. Mutations that increase the levels of long-chain bases suppress nuclear abnormalities of aneuploid yeast independent of karyotype identity. Quantitative lipidomics indicates that long-chain bases are integral components of the nuclear membrane in yeast. Cells isolated from patients with Down syndrome also show that abnormal nuclear morphologies and increases in long-chain bases not only suppress these abnormalities but also improve their fitness. We obtained similar results with cells isolated from patients with Patau or Edward syndrome, indicating that increases in long-chain bases improve the fitness of aneuploid cells in yeast and humans. Targeting lipid biosynthesis pathways represents an important strategy to suppress nuclear abnormalities in aneuploidy-associated diseases. The cellular defects associated with aneuploidy are not well defined. Hwang et al. show that aneuploid yeast and human cells have abnormal nuclear morphology. Targeting ceramide synthesis suppresses nuclear abnormalities and improves the proliferation of aneuploid cells, including cells isolated from patients with Down syndrome.
publishDate 2019
dc.date.none.fl_str_mv 2019-11
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/11336/128464
Hwang, Sunyoung; Williams, Jessica F.; Kneissig, Maja; Lioudyno, Maria; Rivera, Isabel; et al.; Suppressing aneuploidy-associated phenotypes improves the fitness of Trisomy 21 Cells; Elsevier B.V.; Cell Reports; 29; 8; 11-2019; 2473-2488.e5
2211-1247
CONICET Digital
CONICET
url http://hdl.handle.net/11336/128464
identifier_str_mv Hwang, Sunyoung; Williams, Jessica F.; Kneissig, Maja; Lioudyno, Maria; Rivera, Isabel; et al.; Suppressing aneuploidy-associated phenotypes improves the fitness of Trisomy 21 Cells; Elsevier B.V.; Cell Reports; 29; 8; 11-2019; 2473-2488.e5
2211-1247
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S2211124719313737
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2019.10.059
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier B.V.
publisher.none.fl_str_mv Elsevier B.V.
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 13.070432

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