Characterization of Side Population Cells from Human Airway Epithelium

Hackett, Tillie L.; Shaheen, Furquan; Johnson, Andrew D.; Wadsworth, Samuel J.; Pechkovsky, Dmitri V.; Jacoby, David B.; Kicic, Anthony; Stick, Stephen M.; Knight, Darryl A.

doi:10.1634/stemcells.2008-0171

Cited by 124 publications

(88 citation statements)

References 46 publications

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“…There is now good experimental evidence indicating that airway BCs are a population of multipotent stem cells that drives both homeostasis of the normal epithelium and its orderly regeneration after injury (discussed below). This justifies a much more detailed analysis of BC function than has been afforded so far (Jetten, 1991;Randell et al, 1991;Boers et al, 1998;Hong et al, 2004b;Hackett et al, 2008;Rock et al, 2009).…”

Section: Introductionmentioning

confidence: 93%

Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling

Rock

Randell

Hogan

2010

Disease Models &Amp; Mechanisms

651

710

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The small airways of the human lung undergo pathological changes in pulmonary disorders, such as chronic obstructive pulmonary disease (COPD), asthma, bronchiolitis obliterans and cystic fibrosis. These clinical problems impose huge personal and societal healthcare burdens. The changes, termed 'pathological airway remodeling' , affect the epithelium, the underlying mesenchyme and the reciprocal trophic interactions that occur between these tissues. Most of the normal human airway is lined by a pseudostratified epithelium of ciliated cells, secretory cells and 6-30% basal cells, the proportion of which varies along the proximal-distal axis. Epithelial abnormalities range from hypoplasia (failure to differentiate) to basal-and goblet-cell hyperplasia, squamous-and goblet-cell metaplasia, dysplasia and malignant transformation. Mesenchymal alterations include thickening of the basal lamina, smooth muscle hyperplasia, fibrosis and inflammatory cell accumulation. Paradoxically, given the prevalence and importance of airway remodeling in lung disease, its etiology is poorly understood. This is due, in part, to a lack of basic knowledge of the mechanisms that regulate the differentiation, maintenance and repair of the airway epithelium. Specifically, little is known about the proliferation and differentiation of basal cells, a multipotent stem cell population of the pseudostratified airway epithelium. This Perspective summarizes what we know, and what we need to know, about airway basal cells to evaluate their contributions to normal and abnormal airway remodeling. We contend that exploiting well-described model systems using both human airway epithelial cells and the pseudostratified epithelium of the genetically tractable mouse trachea will enable crucial discoveries regarding the pathogenesis of airway disease.

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Section: Introductionmentioning

confidence: 93%

Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling

Rock

Randell

Hogan

2010

Disease Models &Amp; Mechanisms

651

710

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“…Individual sorted TRP63 + BCs demonstrating their capacity to self-renew generate ciliated and secretory cells [15]. Also, human TRP63 + KRT5 + BCs are isolated from normal human airways [85]. These cells, estimated to constitute 0.01% of the total airway epithelium, proliferate and generate ciliated and secretory cells.…”

Section: Goblet Cell Differentiation and Hyperplasia From Stem Cellmentioning

confidence: 99%

Molecular Mechanisms of Metaplasia, Differentiation and Hyperplasia of Goblet Cellin Allergic Asthma

Hayashi¹

2012

J Aller Ther

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Bronchial allergic asthma (asthma) is an airway inflammation characterized by airflow obstruction of variable degrees with bronchial hyper-responsiveness and is induced by a complex interaction of environmental and genetic factors. Asthma of the human can be divided into an immediate-and a late-phase reaction, and some of the patients develop a late-phase reaction after a symptom-free interval. Hallmarks of asthma are mucus overproduction by goblet cells associated with responses of helper T(Th)2 cells. Mucus hypersecretion from goblet cells themselves or by metaplasia and/or hyperplasia of goblet cells appears to be associated with disease severity in asthma, because mucus production by those cells in local bronchial-bronchiolar lesions causes airway mucus plugging. However, the mechanisms of mucus production are not fully understood. Molecular mechanisms of goblet cell metaplasia, differentiation and hyperplasia will be reviewed in this article. Also, the relationship between allergic inflammation in Th1/Th2 paradigm shift and thymic stromal lymphopoietin (TSLP) was included for the understanding of goblet cell response in asthma. The clarification of mechanisms of mucin production in vivo may lead to the development of novel therapeutic strategies to suppress mucus production in asthma.

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“…There is evidence for stem cell niches throughout the airway tree and their capacity to regenerate normal structures has been demonstrated in vitro and in vivo (Borthwick et al, 2001;Hackett et al, 2008;Rock et al, 2009;McQualter, Bertoncello, 2012). Lineage tracing in mice during development, and in adults after injury, suggests that BCs function as long-term stem cells of the airways (Wansleeben et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Cx26 regulates proliferation of repairing basal airway epithelial cells

Crespin

Bacchetta

Saab

et al. 2014

The International Journal of Biochemistry & Cell Biology

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The recovery of an intact epithelium following injury is critical for restoration of lung homeostasis, a process that may be altered in cystic fibrosis (CF). In response to injury, progenitor cells in the undamaged areas migrate, proliferate and re-differentiate to regenerate an intact airway epithelium. The mechanisms regulating this regenerative response are, however, not well understood. In a model of circular wound injury of well-differentiated human airway epithelial cell (HAEC) cultures, we identified the gap junction protein Cx26 as an important regulator of cell proliferation. We report that induction of Cx26 in repairing HAECs is associated with cell proliferation. We also show that Cx26 is expressed in a population of CK14-positive basal-like cells. Cx26 silencing in immortalized cell lines using siRNA and in primary HAECs using lentiviral-transduced shRNA enhanced Ki67-labeling index and Ki67 mRNA, indicating that Cx26 acts a negative regulator of HAEC proliferation.Cx26 silencing also markedly decreased the transcription of KLF4 in immortalized HAECs.We further show that CF HAECs exhibited deregulated expression of KLF4, Ki67 and Cx26 as well enhanced rate of wound closure in the early response to injury. These results point to an altered repair process of CF HAECs characterized by rapid but desynchronized initiation of HAEC activation and proliferation.

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Characterization of Side Population Cells from Human Airway Epithelium

Cited by 124 publications

References 46 publications

Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling

Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling

Molecular Mechanisms of Metaplasia, Differentiation and Hyperplasia of Goblet Cellin Allergic Asthma

Cx26 regulates proliferation of repairing basal airway epithelial cells

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