Journal article
Submucosal Gland Myoepithelial Cells Are Reserve Stem Cells That Can Regenerate Mouse Tracheal Epithelium
Cell stem cell, Vol.22(5), pp.653-667.e5
05/03/2018
DOI: 10.1016/j.stem.2018.03.017
PMCID: PMC5940330
PMID: 29727685
Abstract
The mouse trachea is thought to contain two distinct stem cell compartments that contribute to airway repair—basal cells in the surface airway epithelium (SAE) and an unknown submucosal gland (SMG) cell type. Whether a lineage relationship exists between these two stem cell compartments remains unclear. Using lineage tracing of glandular myoepithelial cells (MECs), we demonstrate that MECs can give rise to seven cell types of the SAE and SMGs following severe airway injury. MECs progressively adopted a basal cell phenotype on the SAE and established lasting progenitors capable of further regeneration following reinjury. MECs activate Wnt-regulated transcription factors (Lef-1/TCF7) following injury and Lef-1 induction in cultured MECs promoted transition to a basal cell phenotype. Surprisingly, dose-dependent MEC conditional activation of Lef-1 in vivo promoted self-limited airway regeneration in the absence of injury. Thus, modulating the Lef-1 transcriptional program in MEC-derived progenitors may have regenerative medicine applications for lung diseases.
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•Myoepithelial cells (MECs) are reserve stem cells for the surface airway epithelium•MECs are multipotent and can lineage commit into seven different cell types•MEC progenitors can establish SAE residence with lasting regenerative capacity•Lef-1 overexpression in MECs is sufficient to induce a regenerative response
Following severe injury to the surface airway epithelium (SAE), Wnt signals activate myoepithelial cells in the submucosal glands (SMGs) to function as reserve stem cells for multipotent basal cells in the SAE and other SMG cell types. Lef-1 activation induces the myoepithelial cell regenerative response and a basal cell-like phenotype.
Details
- Title: Subtitle
- Submucosal Gland Myoepithelial Cells Are Reserve Stem Cells That Can Regenerate Mouse Tracheal Epithelium
- Creators
- Thomas J Lynch - Department of Anatomy & Cell Biology, University of Iowa, Iowa City, IA 52242, USAPreston J Anderson - Department of Anatomy & Cell Biology, University of Iowa, Iowa City, IA 52242, USAPavana G Rotti - Department of Anatomy & Cell Biology, University of Iowa, Iowa City, IA 52242, USAScott R Tyler - Department of Anatomy & Cell Biology, University of Iowa, Iowa City, IA 52242, USAAdrianne K Crooke - Department of Anatomy & Cell Biology, University of Iowa, Iowa City, IA 52242, USASoon H Choi - Department of Anatomy & Cell Biology, University of Iowa, Iowa City, IA 52242, USADaniel T Montoro - Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USACarolyn L Silverman - Department of Anatomy & Cell Biology, University of Iowa, Iowa City, IA 52242, USAWeam Shahin - Department of Anatomy & Cell Biology, University of Iowa, Iowa City, IA 52242, USARui Zhao - Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USAChandler W Jensen-Cody - Department of Anatomy & Cell Biology, University of Iowa, Iowa City, IA 52242, USAAndrea Adamcakova-Dodd - Department of Occupational and Environmental Health, University of Iowa, Iowa City, IA 52242, USAT. Idil Apak Evans - Department of Anatomy & Cell Biology, University of Iowa, Iowa City, IA 52242, USAWeiliang Xie - Department of Anatomy & Cell Biology, University of Iowa, Iowa City, IA 52242, USAYulong Zhang - Department of Anatomy & Cell Biology, University of Iowa, Iowa City, IA 52242, USAHongmei Mou - Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USAB. Paul Herring - Department of Cellular and Integrative Physiology, Indiana University, Indianapolis, IN 46202, USAPeter S Thorne - Department of Occupational and Environmental Health, University of Iowa, Iowa City, IA 52242, USAJayaraj Rajagopal - Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USACharles Yeaman - Department of Anatomy & Cell Biology, University of Iowa, Iowa City, IA 52242, USAKalpaj R Parekh - Department of Cardiothoracic Surgery, University of Iowa, Iowa City, IA 52242, USAJohn F Engelhardt - Department of Anatomy & Cell Biology, University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Cell stem cell, Vol.22(5), pp.653-667.e5
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.stem.2018.03.017
- PMID
- 29727685
- PMCID
- PMC5940330
- ISSN
- 1934-5909
- eISSN
- 1875-9777
- Grant note
- name: NIH, award: DK047967, HL051670, DK054759; name: Carver Chair in Molecular Medicine; name: NIH, award: P30 ES005605
- Language
- English
- Date published
- 05/03/2018
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Civil and Environmental Engineering; Occupational and Environmental Health; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Surgery; Radiation Oncology; Cardiothoracic Surgery; Internal Medicine
- Record Identifier
- 9983997484002771
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