Platform Effects on Regeneration by Pulmonary Basal Cells as Evaluated by Single-Cell RNA Sequencing.
Primary Epithelial Cells
Pulmonary Cell Biology
Regenerative Medicine
Tissue Engineering
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
24 03 2020
24 03 2020
Historique:
received:
19
07
2019
revised:
24
09
2019
accepted:
02
03
2020
entrez:
27
3
2020
pubmed:
27
3
2020
medline:
10
4
2021
Statut:
ppublish
Résumé
Cell-based therapies have shown promise for treating myriad chronic pulmonary diseases through direct application of epithelial progenitors or by way of engineered tissue grafts or whole organs. To elucidate environmental effects on epithelial regenerative outcomes in vitro, here, we isolate and culture a population of pharmacologically expanded basal cells (peBCs) from rat tracheas. At peak basal marker expression, we simultaneously split peBCs into four in vitro platforms: organoid, air-liquid interface (ALI), engineered trachea, and engineered lung. Following differentiation, these samples are evaluated using single-cell RNA sequencing (scRNA-seq) and computational pipelines are developed to compare samples both globally and at the population level. A sample of native rat tracheal epithelium is also evaluated by scRNA-seq as a control for engineered epithelium. Overall, this work identifies platform-specific effects that support the use of engineered models to achieve the most physiologic differential outcomes in pulmonary epithelial regenerative applications.
Identifiants
pubmed: 32209482
pii: S2211-1247(20)30302-8
doi: 10.1016/j.celrep.2020.03.004
pmc: PMC7175071
mid: NIHMS1579443
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
4250-4265.e6Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM007205
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL127349
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NIBIB NIH HHS
ID : R21 EB024889
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL138540
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL145567
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests L.E.N. is a founder of and shareholder in Humacyte, which is a regenerative medicine company. Humacyte produces engineered blood vessels from allogeneic smooth muscle cells for vascular surgery. L.E.N.’s spouse has equity in Humacyte, and L.E.N. serves on Humacyte’s board of directors. L.E.N. is listed as an inventor on patents that are licensed to Humacyte and that produce royalties for L.E.N. L.E.N. has received an unrestricted research gift to support research in her laboratory at Yale University. Humacyte did not fund these studies and Humacyte did not influence the conduct, description, or interpretation of the findings in this article. N.K. served as a consultant to Boehringer Ingelheim, Third Rock, Pliant, Samumed, NuMedii, Indaloo, Theravance, LifeMax, Three Lake Partners, Optikira, and CohBar over the last 3 years and received non-financial support from MiRagen. N.K. is listed as an inventor on several patents and patent applications, none of which are relevant to this manuscript.
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