Diversity of Epithelial Stem Cell Types in Adult Lung

Li, Feng; He, Jieyu; Wei, Jun; Cho, William C.; Liu, Xiaoming

doi:10.1155/2015/728307

Cited by 43 publications

(36 citation statements)

References 94 publications

(198 reference statements)

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“…In contrast, we only observed a moderate contribution of BASCs to homeostatic renewal of the bronchioalveolar epithelium. This finding is in line with the hypothesis that under steady-state conditions, proliferation-competent Club and AT2 cells are the main source for replenishment of the bronchioalveolar epithelium (Giangreco et al, 2009;Hogan et al, 2014;Li et al, 2015). Severe damage of the lung epithelium, however, requires expansion and differentiation of bi-potent BASCs for efficient regeneration.…”

Section: Discussionsupporting

confidence: 88%

Bronchioalveolar stem cells are a main source for regeneration of distal lung epithelia in vivo

et al. 2019

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Bronchioalveolar stem cells (BASCs) are a potential source for lung regeneration, but direct in vivo evidence for a multipotential lineage contribution during homeostasis and disease is critically missing, since specific genetic labeling of BASCs has not been possible. We developed a novel cell tracing approach based on intein‐mediated assembly of newly engineered split‐effectors, allowing selective targeting of dual‐marker expressing BASCs in the mouse lung. RNA sequencing of isolated BASCs demonstrates that BASCs show a distinct transcriptional profile, characterized by co‐expression of bronchiolar and alveolar epithelial genes. We found that BASCs generate the majority of distal lung airway cells after bronchiolar damage but only moderately contribute to cellular turnover under homeostatic conditions. Importantly, DTA‐mediated ablation of BASCs compromised proper regeneration of distal airways. The study defines BASCs as crucial components of the lung repair machinery and provides a paradigmatic example for the detection and manipulation of stem cells that cannot be recognized by a single marker alone.

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Section: Discussionsupporting

confidence: 88%

Bronchioalveolar stem cells are a main source for regeneration of distal lung epithelia in vivo

et al. 2019

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“…Mitochondrial energy drives the functioning of more than 40 types of cells that compose the lung (70). Some of these, like type II alveolar epithelial cells that secrete surfactant or ciliated epithelial and Clara cells that line airways, are highly metabolically active and rich in mitochondria.…”

Section: Connecting Mitochondrial Dysfunction With Lung Diseasementioning

confidence: 99%

Rejuvenating cellular respiration for optimizing respiratory function: targeting mitochondria

Agrawal

Mabalirajan

2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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Altered bioenergetics with increased mitochondrial reactive oxygen species production and degradation of epithelial function are key aspects of pathogenesis in asthma and chronic obstructive pulmonary disease (COPD). This motif is not unique to obstructive airway disease, reported in related airway diseases such as bronchopulmonary dysplasia and parenchymal diseases such as pulmonary fibrosis. Similarly, mitochondrial dysfunction in vascular endothelium or skeletal muscles contributes to the development of pulmonary hypertension and systemic manifestations of lung disease. In experimental models of COPD or asthma, the use of mitochondria-targeted antioxidants, such as MitoQ, has substantially improved mitochondrial health and restored respiratory function. Modulation of noncoding RNA or protein regulators of mitochondrial biogenesis, dynamics, or degradation has been found to be effective in models of fibrosis, emphysema, asthma, and pulmonary hypertension. Transfer of healthy mitochondria to epithelial cells has been associated with remarkable therapeutic efficacy in models of acute lung injury and asthma. Together, these form a 3R model--repair, reprogramming, and replacement--for mitochondria-targeted therapies in lung disease. This review highlights the key role of mitochondrial function in lung health and disease, with a focus on asthma and COPD, and provides an overview of mitochondria-targeted strategies for rejuvenating cellular respiration and optimizing respiratory function in lung diseases.

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“…SP-C, secreted only by AEC II, is a biomarker of these cells (19). Therefore, AEC II were first plated on slides and the SP-C expression was detected in situ using immunofluorescence (Fig.…”

Section: Resultsmentioning

confidence: 99%

Calcitonin gene-related peptide protects type II alveolar epithelial cells from hyperoxia-induced DNA damage and cell death

Zhang

Huang

et al. 2017

Experimental and Therapeutic Medicine

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Hyperoxia therapy for acute lung injury (ALI) may unexpectedly lead to reactive oxygen species (ROS) production and cause additional ALI. Calcitonin gene-related peptide (CGRP) is a 37 amino acid neuropeptide that regulates inflammasome activation. However, the role of CGRP in DNA damage during hyperoxia is unclear. Therefore, the aim of the present study was to investigate the effects of CGRP on DNA damage and the cell death of alveolar epithelial type II cells (AEC II) exposed to 60% oxygen. AEC II were isolated from 19–20 gestational day fetal rat lungs and were exposed to air or to 60% oxygen during treatment with CGRP or the specific CGRP receptor antagonist CGRP8–37. The cells were evaluated using immunofluorescence to examine surfactant protein-C and ROS levels were measured by probing with 2′,7′-dichlorofluorescin diacetate. The apoptosis rate and cell cycle of AEC II were analyzed by flow cytometry, and apoptosis was determined by western blotting analysis of activated caspase 3. The DNA damage was confirmed with immunofluorescence of H2AX via high-content analysis. The ROS levels, apoptotic cell number and the expression of γH2AX were markedly increased in the hyperoxia group compared with those in the air group. Concordantly, ROS levels, apoptotic cell number and the expression of γH2AX were significantly lower with a significant arrest of S and G2/M phases in the CGRP/O2 group than in the hyperoxia or CGRP8–37/O2 groups. CGRP was concluded to protect lung epithelium cells against hyperoxic insult, and upregulation of CGRP may be a possible novel therapeutic target to treat hyperoxic lung injury.

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Diversity of Epithelial Stem Cell Types in Adult Lung

Cited by 43 publications

References 94 publications

Bronchioalveolar stem cells are a main source for regeneration of distal lung epithelia in vivo

Bronchioalveolar stem cells are a main source for regeneration of distal lung epithelia in vivo

Rejuvenating cellular respiration for optimizing respiratory function: targeting mitochondria

Calcitonin gene-related peptide protects type II alveolar epithelial cells from hyperoxia-induced DNA damage and cell death

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