Arrayed CRISPR reveals genetic regulators of tau aggregation, autophagy and mitochondria in Alzheimer’s disease model

Abstract Alzheimer’s disease (AD) is a common neurodegenerative disease with poor prognosis. New options for drug discovery targets are needed. We developed an imaging based arrayed CRISPR method to interrogate the human genome for modulation of in vitro correlates of AD features, and used this to a...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Lishu Duan, Mufeng Hu, Joseph A. Tamm, Yelena Y. Grinberg, Fang Shen, Yating Chai, Hualin Xi, Lauren Gibilisco, Brinda Ravikumar, Vivek Gautam, Eric Karran, Matthew Townsend, Robert V. Talanian
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e41bb5dc26104cbeac5ee6be3c197b17
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e41bb5dc26104cbeac5ee6be3c197b17
record_format	dspace
spelling	oai:doaj.org-article:e41bb5dc26104cbeac5ee6be3c197b172021-12-02T14:06:55ZArrayed CRISPR reveals genetic regulators of tau aggregation, autophagy and mitochondria in Alzheimer’s disease model10.1038/s41598-021-82658-72045-2322https://doaj.org/article/e41bb5dc26104cbeac5ee6be3c197b172021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82658-7https://doaj.org/toc/2045-2322Abstract Alzheimer’s disease (AD) is a common neurodegenerative disease with poor prognosis. New options for drug discovery targets are needed. We developed an imaging based arrayed CRISPR method to interrogate the human genome for modulation of in vitro correlates of AD features, and used this to assess 1525 human genes related to tau aggregation, autophagy and mitochondria. This work revealed (I) a network of tau aggregation modulators including the NF-κB pathway and inflammatory signaling, (II) a correlation between mitochondrial morphology, respiratory function and transcriptomics, (III) machine learning predicted novel roles of genes and pathways in autophagic processes and (IV) individual gene function inferences and interactions among biological processes via multi-feature clustering. These studies provide a platform to interrogate underexplored aspects of AD biology and offer several specific hypotheses for future drug discovery efforts.Lishu DuanMufeng HuJoseph A. TammYelena Y. GrinbergFang ShenYating ChaiHualin XiLauren GibiliscoBrinda RavikumarVivek GautamEric KarranMatthew TownsendRobert V. TalanianNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lishu Duan Mufeng Hu Joseph A. Tamm Yelena Y. Grinberg Fang Shen Yating Chai Hualin Xi Lauren Gibilisco Brinda Ravikumar Vivek Gautam Eric Karran Matthew Townsend Robert V. Talanian Arrayed CRISPR reveals genetic regulators of tau aggregation, autophagy and mitochondria in Alzheimer’s disease model
description	Abstract Alzheimer’s disease (AD) is a common neurodegenerative disease with poor prognosis. New options for drug discovery targets are needed. We developed an imaging based arrayed CRISPR method to interrogate the human genome for modulation of in vitro correlates of AD features, and used this to assess 1525 human genes related to tau aggregation, autophagy and mitochondria. This work revealed (I) a network of tau aggregation modulators including the NF-κB pathway and inflammatory signaling, (II) a correlation between mitochondrial morphology, respiratory function and transcriptomics, (III) machine learning predicted novel roles of genes and pathways in autophagic processes and (IV) individual gene function inferences and interactions among biological processes via multi-feature clustering. These studies provide a platform to interrogate underexplored aspects of AD biology and offer several specific hypotheses for future drug discovery efforts.
format	article
author	Lishu Duan Mufeng Hu Joseph A. Tamm Yelena Y. Grinberg Fang Shen Yating Chai Hualin Xi Lauren Gibilisco Brinda Ravikumar Vivek Gautam Eric Karran Matthew Townsend Robert V. Talanian
author_facet	Lishu Duan Mufeng Hu Joseph A. Tamm Yelena Y. Grinberg Fang Shen Yating Chai Hualin Xi Lauren Gibilisco Brinda Ravikumar Vivek Gautam Eric Karran Matthew Townsend Robert V. Talanian
author_sort	Lishu Duan
title	Arrayed CRISPR reveals genetic regulators of tau aggregation, autophagy and mitochondria in Alzheimer’s disease model
title_short	Arrayed CRISPR reveals genetic regulators of tau aggregation, autophagy and mitochondria in Alzheimer’s disease model
title_full	Arrayed CRISPR reveals genetic regulators of tau aggregation, autophagy and mitochondria in Alzheimer’s disease model
title_fullStr	Arrayed CRISPR reveals genetic regulators of tau aggregation, autophagy and mitochondria in Alzheimer’s disease model
title_full_unstemmed	Arrayed CRISPR reveals genetic regulators of tau aggregation, autophagy and mitochondria in Alzheimer’s disease model
title_sort	arrayed crispr reveals genetic regulators of tau aggregation, autophagy and mitochondria in alzheimer’s disease model
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e41bb5dc26104cbeac5ee6be3c197b17
work_keys_str_mv	AT lishuduan arrayedcrisprrevealsgeneticregulatorsoftauaggregationautophagyandmitochondriainalzheimersdiseasemodel AT mufenghu arrayedcrisprrevealsgeneticregulatorsoftauaggregationautophagyandmitochondriainalzheimersdiseasemodel AT josephatamm arrayedcrisprrevealsgeneticregulatorsoftauaggregationautophagyandmitochondriainalzheimersdiseasemodel AT yelenaygrinberg arrayedcrisprrevealsgeneticregulatorsoftauaggregationautophagyandmitochondriainalzheimersdiseasemodel AT fangshen arrayedcrisprrevealsgeneticregulatorsoftauaggregationautophagyandmitochondriainalzheimersdiseasemodel AT yatingchai arrayedcrisprrevealsgeneticregulatorsoftauaggregationautophagyandmitochondriainalzheimersdiseasemodel AT hualinxi arrayedcrisprrevealsgeneticregulatorsoftauaggregationautophagyandmitochondriainalzheimersdiseasemodel AT laurengibilisco arrayedcrisprrevealsgeneticregulatorsoftauaggregationautophagyandmitochondriainalzheimersdiseasemodel AT brindaravikumar arrayedcrisprrevealsgeneticregulatorsoftauaggregationautophagyandmitochondriainalzheimersdiseasemodel AT vivekgautam arrayedcrisprrevealsgeneticregulatorsoftauaggregationautophagyandmitochondriainalzheimersdiseasemodel AT erickarran arrayedcrisprrevealsgeneticregulatorsoftauaggregationautophagyandmitochondriainalzheimersdiseasemodel AT matthewtownsend arrayedcrisprrevealsgeneticregulatorsoftauaggregationautophagyandmitochondriainalzheimersdiseasemodel AT robertvtalanian arrayedcrisprrevealsgeneticregulatorsoftauaggregationautophagyandmitochondriainalzheimersdiseasemodel
_version_	1718391995625373696

Arrayed CRISPR reveals genetic regulators of tau aggregation, autophagy and mitochondria in Alzheimer’s disease model

Ejemplares similares