Patient-specific iPSCs carrying an SFTPC mutation reveal the intrinsic alveolar epithelial dysfunction at the inception of interstitial lung disease.


Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
31 08 2021
Historique:
received: 18 11 2020
revised: 28 04 2021
accepted: 06 08 2021
entrez: 1 9 2021
pubmed: 2 9 2021
medline: 15 2 2022
Statut: ppublish

Résumé

Alveolar epithelial type 2 cell (AEC2) dysfunction is implicated in the pathogenesis of adult and pediatric interstitial lung disease (ILD), including idiopathic pulmonary fibrosis (IPF); however, identification of disease-initiating mechanisms has been impeded by inability to access primary AEC2s early on. Here, we present a human in vitro model permitting investigation of epithelial-intrinsic events culminating in AEC2 dysfunction, using patient-specific induced pluripotent stem cells (iPSCs) carrying an AEC2-exclusive disease-associated variant (SFTPC

Identifiants

pubmed: 34469722
pii: S2211-1247(21)01079-2
doi: 10.1016/j.celrep.2021.109636
pmc: PMC8432578
mid: NIHMS1737383
pii:
doi:

Substances chimiques

Inflammation Mediators 0
NF-kappa B 0
Pulmonary Surfactant-Associated Protein C 0
SFTPC protein, human 0
Sftpc protein, mouse 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

109636

Subventions

Organisme : NHLBI NIH HHS
ID : R01 HL119436
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL150617
Pays : United States
Organisme : NCATS NIH HHS
ID : U01 TR001810
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL149853
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL152976
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL152970
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL145408
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES013508
Pays : United States
Organisme : BLRD VA
ID : I01 BX001176
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001430
Pays : United States
Organisme : NHLBI NIH HHS
ID : K24 HL143281
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL134745
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL095993
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA026914
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL134766
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL148692
Pays : United States

Informations de copyright

Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

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Auteurs

Konstantinos-Dionysios Alysandratos (KD)

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

Scott J Russo (SJ)

Pulmonary, Allergy, and Critical Care Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; PENN-CHOP Lung Biology Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.

Anton Petcherski (A)

Departments of Medicine, Endocrinology and Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.

Evan P Taddeo (EP)

Departments of Medicine, Endocrinology and Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.

Rebeca Acín-Pérez (R)

Departments of Medicine, Endocrinology and Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.

Carlos Villacorta-Martin (C)

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

J C Jean (JC)

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

Surafel Mulugeta (S)

Pulmonary, Allergy, and Critical Care Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; PENN-CHOP Lung Biology Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.

Luis R Rodriguez (LR)

Pulmonary, Allergy, and Critical Care Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; PENN-CHOP Lung Biology Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.

Benjamin C Blum (BC)

Departments of Biology and Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.

Ryan M Hekman (RM)

Departments of Biology and Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.

Olivia T Hix (OT)

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

Kasey Minakin (K)

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

Marall Vedaie (M)

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

Seunghyi Kook (S)

Department of Pediatrics, Monroe Carell Jr. Children's Hospital, Vanderbilt University, Nashville, TN 37232, USA.

Andrew M Tilston-Lunel (AM)

Departments of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.

Xaralabos Varelas (X)

Departments of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.

Jennifer A Wambach (JA)

Division of Newborn Medicine, Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, MO 63110, USA.

F Sessions Cole (FS)

Division of Newborn Medicine, Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, MO 63110, USA.

Aaron Hamvas (A)

Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.

Lisa R Young (LR)

Division of Pulmonary and Sleep Medicine, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

Marc Liesa (M)

Departments of Medicine, Endocrinology and Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.

Andrew Emili (A)

Departments of Biology and Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.

Susan H Guttentag (SH)

Department of Pediatrics, Monroe Carell Jr. Children's Hospital, Vanderbilt University, Nashville, TN 37232, USA.

Orian S Shirihai (OS)

Departments of Medicine, Endocrinology and Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.

Michael F Beers (MF)

Pulmonary, Allergy, and Critical Care Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; PENN-CHOP Lung Biology Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. Electronic address: mfbeers@pennmedicine.upenn.edu.

Darrell N Kotton (DN)

Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address: dkotton@bu.edu.

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Classifications MeSH