CRISPR interference interrogation of COPD GWAS genes reveals the functional significance of desmoplakin in iPSC-derived alveolar epithelial cells.


Journal

Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440

Informations de publication

Date de publication:
15 07 2022
Historique:
entrez: 20 7 2022
pubmed: 21 7 2022
medline: 23 7 2022
Statut: ppublish

Résumé

Genome-wide association studies (GWAS) have identified dozens of loci associated with chronic obstructive pulmonary disease (COPD) susceptibility; however, the function of associated genes in the cell type(s) affected in disease remains poorly understood, partly due to a lack of cell models that recapitulate human alveolar biology. Here, we apply CRISPR interference to interrogate the function of nine genes implicated in COPD by GWAS in induced pluripotent stem cell-derived type 2 alveolar epithelial cells (iAT2s). We find that multiple genes implicated by GWAS affect iAT2 function, including differentiation potential, maturation, and/or proliferation. Detailed characterization of the GWAS gene

Identifiants

pubmed: 35857525
doi: 10.1126/sciadv.abo6566
pmc: PMC9278866
doi:

Substances chimiques

Desmoplakins 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

eabo6566

Subventions

Organisme : NHLBI NIH HHS
ID : F30 HL147426
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL137927
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL148667
Pays : United States

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Auteurs

Rhiannon B Werder (RB)

Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA.
Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia.

Tao Liu (T)

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Kristine M Abo (KM)

Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA.
Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.

Jonathan Lindstrom-Vautrin (J)

Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA.

Carlos Villacorta-Martin (C)

Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA.

Jessie Huang (J)

Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA.
Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.

Anne Hinds (A)

Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.

Nathan Boyer (N)

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Esther Bullitt (E)

Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118, USA.

Marc Liesa (M)

Department of Medicine, Endocrinology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA 90095, USA.
Institut de Biologia Molecular De Barcelona (IBMB-CSIC), Barcelona, Catalonia 08028, Spain.

Edwin K Silverman (EK)

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Darrell N Kotton (DN)

Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA.
Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.

Michael H Cho (MH)

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Xiaobo Zhou (X)

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Andrew A Wilson (AA)

Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA.
Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.

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Classifications MeSH