Submucosal Gland Myoepithelial Cells Are Reserve Stem Cells That Can Regenerate Mouse Tracheal Epithelium

Thomas J. Lynch, Preston J. Anderson, Pavana G. Rotti, Scott R. Tyler, Adrianne K. Crooke, Soon H. Choi, Daniel T. Montoro, Carolyn L. Silverman, Weam Shahin, Rui Zhao, Chandler W. Jensen-Cody, Andrea Adamcakova-Dodd, T. Idil Apak Evans, Weiliang Xie, Yulong Zhang, Hongmei Mou, B. Herring, Peter S. Thorne, Jayaraj Rajagopal, Charles Yeaman & 2 others Kalpaj R. Parekh, John F. Engelhardt

Research output: Contribution to journalArticle

12 Citations (Scopus)

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. 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.

Original languageEnglish (US)
JournalCell Stem Cell
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Stem Cells
Epithelium
Wounds and Injuries
Phenotype
Regeneration
Multipotent Stem Cells
Regenerative Medicine
Trachea
Lung Diseases
Cultured Cells
Transcription Factors

Keywords

  • airway basal cell
  • injury repair
  • LEF1
  • lineage-trace
  • lymphoid enhancer-binding factor-1
  • multipotency
  • myoepithelial cell
  • plasticity

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

Cite this

Lynch, T. J., Anderson, P. J., Rotti, P. G., Tyler, S. R., Crooke, A. K., Choi, S. H., ... Engelhardt, J. F. (Accepted/In press). Submucosal Gland Myoepithelial Cells Are Reserve Stem Cells That Can Regenerate Mouse Tracheal Epithelium. Cell Stem Cell. https://doi.org/10.1016/j.stem.2018.03.017

Submucosal Gland Myoepithelial Cells Are Reserve Stem Cells That Can Regenerate Mouse Tracheal Epithelium. / Lynch, Thomas J.; Anderson, Preston J.; Rotti, Pavana G.; Tyler, Scott R.; Crooke, Adrianne K.; Choi, Soon H.; Montoro, Daniel T.; Silverman, Carolyn L.; Shahin, Weam; Zhao, Rui; Jensen-Cody, Chandler W.; Adamcakova-Dodd, Andrea; Evans, T. Idil Apak; Xie, Weiliang; Zhang, Yulong; Mou, Hongmei; Herring, B.; Thorne, Peter S.; Rajagopal, Jayaraj; Yeaman, Charles; Parekh, Kalpaj R.; Engelhardt, John F.

In: Cell Stem Cell, 01.01.2018.

Research output: Contribution to journalArticle

Lynch, TJ, Anderson, PJ, Rotti, PG, Tyler, SR, Crooke, AK, Choi, SH, Montoro, DT, Silverman, CL, Shahin, W, Zhao, R, Jensen-Cody, CW, Adamcakova-Dodd, A, Evans, TIA, Xie, W, Zhang, Y, Mou, H, Herring, B, Thorne, PS, Rajagopal, J, Yeaman, C, Parekh, KR & Engelhardt, JF 2018, 'Submucosal Gland Myoepithelial Cells Are Reserve Stem Cells That Can Regenerate Mouse Tracheal Epithelium', Cell Stem Cell. https://doi.org/10.1016/j.stem.2018.03.017
Lynch, Thomas J. ; Anderson, Preston J. ; Rotti, Pavana G. ; Tyler, Scott R. ; Crooke, Adrianne K. ; Choi, Soon H. ; Montoro, Daniel T. ; Silverman, Carolyn L. ; Shahin, Weam ; Zhao, Rui ; Jensen-Cody, Chandler W. ; Adamcakova-Dodd, Andrea ; Evans, T. Idil Apak ; Xie, Weiliang ; Zhang, Yulong ; Mou, Hongmei ; Herring, B. ; Thorne, Peter S. ; Rajagopal, Jayaraj ; Yeaman, Charles ; Parekh, Kalpaj R. ; Engelhardt, John F. / Submucosal Gland Myoepithelial Cells Are Reserve Stem Cells That Can Regenerate Mouse Tracheal Epithelium. In: Cell Stem Cell. 2018.
@article{4a940db739674f45829293ef0e934c5d,
title = "Submucosal Gland Myoepithelial Cells Are Reserve Stem Cells That Can Regenerate Mouse Tracheal Epithelium",
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. 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.",
keywords = "airway basal cell, injury repair, LEF1, lineage-trace, lymphoid enhancer-binding factor-1, multipotency, myoepithelial cell, plasticity",
author = "Lynch, {Thomas J.} and Anderson, {Preston J.} and Rotti, {Pavana G.} and Tyler, {Scott R.} and Crooke, {Adrianne K.} and Choi, {Soon H.} and Montoro, {Daniel T.} and Silverman, {Carolyn L.} and Weam Shahin and Rui Zhao and Jensen-Cody, {Chandler W.} and Andrea Adamcakova-Dodd and Evans, {T. Idil Apak} and Weiliang Xie and Yulong Zhang and Hongmei Mou and B. Herring and Thorne, {Peter S.} and Jayaraj Rajagopal and Charles Yeaman and Parekh, {Kalpaj R.} and Engelhardt, {John F.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.stem.2018.03.017",
language = "English (US)",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",

}

TY - JOUR

T1 - Submucosal Gland Myoepithelial Cells Are Reserve Stem Cells That Can Regenerate Mouse Tracheal Epithelium

AU - Lynch, Thomas J.

AU - Anderson, Preston J.

AU - Rotti, Pavana G.

AU - Tyler, Scott R.

AU - Crooke, Adrianne K.

AU - Choi, Soon H.

AU - Montoro, Daniel T.

AU - Silverman, Carolyn L.

AU - Shahin, Weam

AU - Zhao, Rui

AU - Jensen-Cody, Chandler W.

AU - Adamcakova-Dodd, Andrea

AU - Evans, T. Idil Apak

AU - Xie, Weiliang

AU - Zhang, Yulong

AU - Mou, Hongmei

AU - Herring, B.

AU - Thorne, Peter S.

AU - Rajagopal, Jayaraj

AU - Yeaman, Charles

AU - Parekh, Kalpaj R.

AU - Engelhardt, John F.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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. 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.

AB - 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. 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.

KW - airway basal cell

KW - injury repair

KW - LEF1

KW - lineage-trace

KW - lymphoid enhancer-binding factor-1

KW - multipotency

KW - myoepithelial cell

KW - plasticity

UR - http://www.scopus.com/inward/record.url?scp=85044986008&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044986008&partnerID=8YFLogxK

U2 - 10.1016/j.stem.2018.03.017

DO - 10.1016/j.stem.2018.03.017

M3 - Article

JO - Cell Stem Cell

JF - Cell Stem Cell

SN - 1934-5909

ER -