High-dimensional phenotyping to define the genetic basis of cellular morphology.

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
06 Jan 2024
Historique:
received: 06 02 2023
accepted: 28 11 2023
medline: 7 1 2024
pubmed: 7 1 2024
entrez: 6 1 2024
Statut: epublish

Résumé

The morphology of cells is dynamic and mediated by genetic and environmental factors. Characterizing how genetic variation impacts cell morphology can provide an important link between disease association and cellular function. Here, we combine genomic sequencing and high-content imaging approaches on iPSCs from 297 unique donors to investigate the relationship between genetic variants and cellular morphology to map what we term cell morphological quantitative trait loci (cmQTLs). We identify novel associations between rare protein altering variants in WASF2, TSPAN15, and PRLR with several morphological traits related to cell shape, nucleic granularity, and mitochondrial distribution. Knockdown of these genes by CRISPRi confirms their role in cell morphology. Analysis of common variants yields one significant association and nominate over 300 variants with suggestive evidence (P < 10

Identifiants

DOI: 10.1038/s41467-023-44045-w PMID: 38184653
pubmed: 38184653
doi: 10.1038/s41467-023-44045-w
pii: 10.1038/s41467-023-44045-w
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

347

Subventions

Organisme : NIMH NIH HHS
ID : U01 MH115727
Pays : United States

Informations de copyright

© 2024. The Author(s).

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Auteurs

Matthew Tegtmeyer (M)

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
Centre for Gene Therapy and Regenerative Medicine, King's College, London, UK.
ORCID: 0000-0002-9032-8207

Jatin Arora (J)

Center for Data Sciences, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Samira Asgari (S)

Center for Data Sciences, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
ORCID: 0000-0002-2347-8985

Beth A Cimini (BA)

Imaging Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
ORCID: 0000-0001-9640-9318

Ajay Nadig (A)

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.

Emily Peirent (E)

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Dhara Liyanage (D)

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Gregory P Way (GP)

Imaging Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
ORCID: 0000-0002-0503-9348

Erin Weisbart (E)

Imaging Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
ORCID: 0000-0002-6437-2458

Aparna Nathan (A)

Center for Data Sciences, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0002-5975-2851

Tiffany Amariuta (T)

Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Halıcıoğlu Data Science Institute, University of California, La Jolla, CA, USA.
Department of Medicine, University of California, La Jolla, CA, USA.

Kevin Eggan (K)

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
ORCID: 0000-0003-4436-8467

Marzieh Haghighi (M)

Imaging Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
ORCID: 0000-0002-0867-8364

Steven A McCarroll (SA)

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Department of Genetics, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0002-6954-8184

Luke O'Connor (L)

Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0003-2730-9668

Anne E Carpenter (AE)

Imaging Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
ORCID: 0000-0003-1555-8261

Shantanu Singh (S)

Imaging Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA. shsingh@broadinstitute.org.
ORCID: 0000-0003-3150-3025

Ralda Nehme (R)

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. rnehme@broadinstitute.org.
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA. rnehme@broadinstitute.org.
ORCID: 0000-0001-7215-3311

Soumya Raychaudhuri (S)

Center for Data Sciences, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. soumya@broadinstitute.org.
Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. soumya@broadinstitute.org.
Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. soumya@broadinstitute.org.
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. soumya@broadinstitute.org.
Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. soumya@broadinstitute.org.
Centre for Genetics and Genomics Versus Arthritis, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK. soumya@broadinstitute.org.
ORCID: 0000-0002-1901-8265

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