Bronchiolar Progenitor Cells

Chen, Huaiyong; Matsumoto, Keitaro; Stripp, Barry R.

doi:10.1513/pats.200907-078rm

Cited by 22 publications

(16 citation statements)

References 46 publications

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“…Unipotent progenitors with distinct differentiation potential would have to be simultaneously activated to form functionally competent gas-exchange units. This limitation is shared by bronchoalveolar stem cells, Clara cells, side population cells, and type II alveolar epithelial cells, since they generate only type I and type II pneumocytes 3,4,6–9,27 or stromal cells. 10 Similarly, bone marrow cells expressing Clara-cell secretory protein transdifferentiate and acquire the phenotype of epithelial-cell lineages 31 but lack the ability to replace and integrate the other components of the gas-exchange unit.…”

Section: Discussionmentioning

confidence: 99%

Evidence for Human Lung Stem Cells

et al. 2011

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BACKGROUND Although progenitor cells have been described in distinct anatomical regions of the lung, description of resident stem cells has remained elusive. METHODS Surgical lung-tissue specimens were studied in situ to identify and characterize human lung stem cells. We defined their phenotype and functional properties in vitro and in vivo. RESULTS Human lungs contain undifferentiated human lung stem cells nested in niches in the distal airways. These cells are self-renewing, clonogenic, and multipotent in vitro. After injection into damaged mouse lung in vivo, human lung stem cells form human bronchioles, alveoli, and pulmonary vessels integrated structurally and functionally with the damaged organ. The formation of a chimeric lung was confirmed by detection of human transcripts for epithelial and vascular genes. In addition, the self-renewal and long-term proliferation of human lung stem cells was shown in serial-transplantation assays. CONCLUSIONS Human lungs contain identifiable stem cells. In animal models, these cells participate in tissue homeostasis and regeneration. They have the undemonstrated potential to promote tissue restoration in patients with lung disease. (Funded by the National Institutes of Health.)

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Section: Discussionmentioning

confidence: 99%

Evidence for Human Lung Stem Cells

et al. 2011

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“…Basal cells have been considered as the source of cell renewal in adult pseudostratified epithelia, such as the airway tract, the mammary gland, and the prostate (Rizzo et al 2005, Chen et al 2009, Rock et al 2009, 2010, Cole et al 2010, Van Keymeulen et al 2012). In this study, we found that while clear cells appeared simultaneously with basal cells in the different epididymal regions during postnatal development, they were detected at a discrete distance from each other at their onset of differentiation.…”

Section: Discussionmentioning

confidence: 99%

Plasticity of basal cells during postnatal development in the rat epididymis

et al. 2013

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Our previous study has shown that basal cells sense luminal factors by forming a narrow body projection that can cross epithelial tight junctions. As a first step toward characterizing the structural plasticity of basal cells, in this study, we followed their appearance and morphology in the rat epididymis and vas deferens (VD) during postnatal development and examined their modulation by androgens in adulthood. Immunofluorescence labeling for cytokeratin 5 showed that basal cells are absent at birth. They progressively appear in a retrograde manner from the VD and cauda epididymis to the initial segments during the postnatal weeks PNW1–3. At the onset of differentiation, basal cells are in contact with the lumen and their nucleus is located at the same level as that of adjacent epithelial cells. Basal cells then position their nucleus to the base of the epithelium, and while some are still in contact with the lumen, others have a ‘dome-shaped’ appearance. At PNW5–6, basal cells form a loose network at the base of the epithelium, and luminal-reaching basal cells are rarely detected. The arrival of spermatozoa during PNW7–8 did not trigger the development of projections in basal cells. However, cells with a narrow luminal-reaching projection began to reappear between PNW8 and PNW12 in the corpus and the cauda. Treatment with flutamide from PNW10 to PNW12 significantly reduced the number of luminal-reaching basal cell projections. In summary, basal cells exhibit significant structural plasticity during differentiation. Fewer apical-reaching projections were detected after flutamide treatment in adulthood, indicating the role of androgens in the luminal-sensing function of basal cells.

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“…TOPGAL mice were a gift from E. β-gal staining. Tissues containing Rosa26R, TOPGAL, or Fgf10 LacZ alleles were dissected, and β-gal staining was performed at different stages after naphthalene injury (3,7,14, and 21 days). Lungs were dissected and fixed in 4% PFA in PBS at room temperature for 5 minutes, rinsed in PBS, injected with freshly prepared X-gal solution, transferred into a vial of X-gal solution, and stained at 37°C overnight.…”

Section: Methodsmentioning

confidence: 99%

“…However, little is known about the activation mechanism of these latent stem cells (reviewed in refs. 3,4). Knowledge about the pathways involved in the activation of these latent epithelial stem cells could enable new therapeutic strategies for treatment of lung disease.…”

Section: Introductionmentioning

confidence: 99%

Parabronchial smooth muscle constitutes an airway epithelial stem cell niche in the mouse lung after injury

Volckaert¹,

Dill²,

Campbell³

et al. 2011

J. Clin. Invest.

207

239

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During lung development, parabronchial SMC (PSMC) progenitors in the distal mesenchyme secrete fibroblast growth factor 10 (Fgf10), which acts on distal epithelial progenitors to promote their proliferation. β-catenin signaling within PSMC progenitors is essential for their maintenance, proliferation, and expression of Fgf10. Here, we report that this Wnt/Fgf10 embryonic signaling cascade is reactivated in mature PSMCs after naphthalene-induced injury to airway epithelium. Furthermore, we found that this paracrine Fgf10 action was essential for activating surviving variant Clara cells (the cells in the airway epithelium from which replacement epithelial cells originate) located at the bronchoalveolar duct junctions and adjacent to neuroendocrine bodies. After naphthalene injury, PSMCs secreted Fgf10 to activate Notch signaling and induce Snai1 expression in surviving variant Clara cells, which subsequently underwent a transient epithelial to mesenchymal transition to initiate the repair process. Epithelial Snai1 expression was important for regeneration after injury. We have therefore identified PSMCs as a stem cell niche for the variant Clara cells in the lung and established that paracrine Fgf10 signaling from the niche is critical for epithelial repair after naphthalene injury. These findings also have implications for understanding the misregulation of lung repair in asthma and cancer.

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Bronchiolar Progenitor Cells

Cited by 22 publications

References 46 publications

Evidence for Human Lung Stem Cells

Evidence for Human Lung Stem Cells

Plasticity of basal cells during postnatal development in the rat epididymis

Parabronchial smooth muscle constitutes an airway epithelial stem cell niche in the mouse lung after injury

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