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Stem Cell Niches in the Lung

  • Chapter
Lung Stem Cells in the Epithelium and Vasculature

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

  • 1061 Accesses

Abstract

In the context of homeostasis, cellular turnover in the airways of the lung is very low. Following injury, however, the lung can undergo dramatic regeneration and repair, which is imparted by region-specific stem/progenitor cells residing in distinct niches along the proximal-to-distal axis of the airway tree. Each niche has unique biologic characteristics, and controls the specification of lung stem/progenitor cells in proportion to the type and degree of injury. Evidence for the existence of physiologically and spatially distinct stem/progenitor cell populations in the mouse lung comes from in vivo lineage tracing experiments in genetically engineered mice, and from in vitro and ex vivo analyses in which phenotypic markers were used to isolate distinct stem/progenitor cell populations. Distinct, region-specific stem cell types in the mouse airway include basal-like cells in the ducts of submucosal glands (SMGs), basal cells in intercartilaginous regions of the proximal trachea and bronchi, variant club cells (formerly termed Clara cells) in the neuroendocrine bodies (NEBs) of bronchioles, bronchioalveolar stem cells (BASCs) at bronchioalveolar duct junctions (BADJs) in the respiratory bronchioles, and alveolar type II cells in the alveolar space. In this chapter, we review recent findings regarding the identification and isolation of region-specific stem/progenitor cells and properties of their niches in the lung.

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Abbreviations

AEC I/II:

Alveolar epithelial cell I/II

AF:

Autofluorescence

ALDH1:

Aldehyde dehydrogenase 1 family

AQP3:

Aquaporin 3

BADJ:

Bronchioalveolar duct junction

BASC:

Bronchioalveolar stem cell

CCSP:

Club cell secretory protein

CD16:

Fc receptor, IgG, low affinity III

CD24:

CD24 molecule

CD31:

Platelet/Endothelial cell adhesion molecule 1 (aka PECAM1)

CD32:

Fc receptor, IgG, low affinity IIb

CD34:

CD34 antigen

CD45:

Protein tyrosine phosphatase, receptor type, C (aka Ptprc)

CD73:

5′ Nucleotidase, Ecto (aka Nt5e)

CD151:

CD151 antigen

CDH1:

Cadherin 1, type 1, E-cadherin (aka E-Cad)

CFTR:

Cystic fibrosis transmembrane conductance regulator

CGRP:

Calcitonin gene-related peptide

CK:

Cytokeratin

CSC:

Cancer stem cell

EpCAM:

Epithelial cell adhesion molecule

F3:

Tissue factor (aka TF)

FGF:

Fibroblast growth factor

GSI-A3B:

Griffonia simplicifolia isolectin A3B

H33342:

Hoechst 33342

ITGA6:

Integrin alpha 6 (aka CD49f)

ITGB4:

Integrin beta 4 (aka CD104)

LGR6:

Leucine-rich repeat containing g protein-coupled receptor 6

LRC:

Label retaining cell

Ly6a:

Lymphocyte antigen 6 complex, locus A (aka Sca-1)

Ly76:

Lymphocyte antigen 76 (aka TER119)

lrMSC:

Lung-resident mesenchymal stromal cell

MSC:

Mesenchymal stromal cell

NEB:

Neuroendocrine body

NGFR:

Nerve growth factor receptor

NSCLC:

Non-small cell lung cancer

PDGFRα:

Platelet-derived growth factor receptor alpha

PNEC:

Pulmonary neuroendocrine cell

SAE:

Surface airway epithelium

SCLC:

Small cell lung cancer

SMG:

Submucosal gland

SPC:

Surfactant protein C (aka Sftpc)

TGFβ:

Transforming growth factor beta

TROP2:

Tumor-associated calcium signal transducer 2 (aka Tacstd2)

TTF1:

Thyroid transcription factor 1 (aka NKx2.1)

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Acknowledgment

This work was supported by grants from the NIH (DK047967) and the University of Iowa Center for Gene Therapy (DK054759).

Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, 51 Newton Road, Room 1-111 BSB, Iowa City, IA, 52242, USA

    Thomas J. Lynch, Xiaoming Liu & John F. Engelhardt

  2. Institute of Human Stem Cell Research, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, IA, 750004, China

    Xiaoming Liu & Jun Wei

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  1. Thomas J. Lynch
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  2. Xiaoming Liu
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  3. Jun Wei
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  4. John F. Engelhardt
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Correspondence to John F. Engelhardt .

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  1. Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, California, USA

    Amy Firth

  2. Department of Medicine, The Univsersity of Arizona, Tucson, Arizona, USA

    Jason X.-J. Yuan

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Lynch, T.J., Liu, X., Wei, J., Engelhardt, J.F. (2015). Stem Cell Niches in the Lung. In: Firth, A., Yuan, JJ. (eds) Lung Stem Cells in the Epithelium and Vasculature. Stem Cell Biology and Regenerative Medicine. Springer, Cham. https://doi.org/10.1007/978-3-319-16232-4_3

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