Embryonic mouse lung epithelial progenitor cells co-express immunohistochemical markers of diverse mature cell lineages.

Wuenschell, Carol; Sunday, Mary E.; Singh, Gurmukh; Minoo, Parviz; Slavkin, Harold C.; Warburton, David

doi:10.1177/44.2.8609367

Cited by 106 publications

(74 citation statements)

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“…Hyperplasia of such a cell type could give rise to both EH and adenomas. Coexpression of protein markers for Clara cells and type II cells is known to occur in epithelial progenitor cells during embryonic development in the mouse and other mammals (Wuenschell et al 1996). However, no such stem cell has been identified in the adult lung.…”

Section: Discussionmentioning

confidence: 99%

Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras

Jackson¹,

Willis²,

Mercer³

et al. 2001

Genes Dev.

1,746

1,849

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Adenocarcinoma of the lung is the most common form of lung cancer, but the cell of origin and the stages of progression of this tumor type are not well understood. We have developed a new model of lung adenocarcinoma in mice harboring a conditionally activatable allele of oncogenic K-ras. Here we show that the use of a recombinant adenovirus expressing Cre recombinase (AdenoCre) to induce K-ras G12D expression in the lungs of mice allows control of the timing and multiplicity of tumor initiation. Through the ability to synchronize tumor initiation in these mice, we have been able to characterize the stages of tumor progression. Of particular significance, this system has led to the identification of a new cell type contributing to the development of pulmonary adenocarcinoma.

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Section: Discussionmentioning

confidence: 99%

Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras

Jackson¹,

Willis²,

Mercer³

et al. 2001

Genes Dev.

1,746

1,849

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show abstract

“…The proliferation appears to extend from the terminal bronchi where it is believed epithelial progenitor cells, including those giving rise to epithelial cancer, may be concentrated (44). The proliferating cells stain for both protein C and TTF, as would be expected for putative lung epithelial progenitor cells (55). In WT mice, this proliferation appears to be self-limiting, but in SCID mice or mice depleted of Tregs, it continues and may result in death.…”

Section: Epithelial Proliferationmentioning

confidence: 91%

Intraepithelial T-Cell Cytotoxicity, Induced Bronchus-Associated Lymphoid Tissue, and Proliferation of Pneumocytes in Experimental Mouse Models of Influenza

Sell

Guest²,

McKinstry³

et al. 2014

Viral Immunology

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Immunopathologic examination of the lungs of mice with experimental influenza virus infection reveals three prominent findings. (i) There is rapidly developing perivasuclar (arterial) and peribronchial infiltration with Tcells and invasion of T-cells into the bronchiolar epithelium, separation of epithelial cells from each other and from the basement membrane, leading to defoliation of the bronchial epithelium. This reaction is analogous to a viral exanthema of the skin, such as measles and smallpox. This previously described but unappreciated reaction most likely is an effective way to eliminate virus-infected cells, but may contribute to acute toxicity and mortality.(ii) After this, there is formation of dense collections of lymphocytes adjacent to bronchi consisting mainly of Bcells, with a scattering of T-cells and macrophages. This is known as induced bronchial-associated lymphoid tissue (iBALT) and correlates with increased interleukin (IL)-17 in the lung. iBALT provides sites for a local immune reaction in the lung to both the original infection and related viral infections (heterologous immunity). (iii) Within the first 2-3 weeks, there is proliferation of type II pneumocytes and/or terminal bronchial epithelial cells extending from the terminal bronchioles into the adjacent alveoli, eventually leading to large zones of the lung filled with tumor-like epithelial cells with squamous metaplasia. The proliferation correlates with IL-17 and IL-22 expression, and the extent of this reaction appears to be determined by the availability of T-regulatory cells.

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“…The accumulation of the SP-B þ /CC10 þ /Bmi1 þ /SP-C -cells suggests that differentiation of the lung epithelial progenitor cells was impaired in the Runx3À/À bronchioli. Lung epithelial progenitor cells express both alveolar-specific and bronchiolarspecific markers (Wuenschell et al, 1996). For example, the BASCs express both SP-C and CC10.…”

Section: Role Of Runx3 In Lung Tumorigenesis K-s Lee Et Almentioning

confidence: 99%

“…During days 13-15 of early embryo development (E13-E15, early phase), the expression of cell surface markers is identical in all epithelial cells. The late phase (E16-E18) is characterized by the emergence of differentiated cell types for alveoli and bronchioli (Wuenschell et al, 1996). The alveolar epithelium includes alveolar epithelial type 1 (AT1) and AT2 cells, which are derived from common alveolar stem cells (AT2 cells) (Bishop, 2004;Reddy et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Runx3 is required for the differentiation of lung epithelial cells and suppression of lung cancer

Lee

et al. 2010

Oncogene

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Human lung adenocarcinoma, the most prevalent form of lung cancer, is characterized by many molecular abnormalities. K-ras mutations are associated with the initiation of lung adenocarcinomas, but K-ras-independent mechanisms may also initiate lung tumors. Here, we find that the runt-related transcription factor Runx3 is essential for normal murine lung development and is a tumor suppressor that prevents lung adenocarcinoma. Runx3À/À mice, which die soon after birth, exhibit alveolar hyperplasia. Importantly, Runx3À/À bronchioli exhibit impaired differentiation, as evidenced by the accumulation of epithelial cells containing specific markers for both alveolar (that is SP-B) and bronchiolar (that is CC10) lineages. Runx3À/À epithelial cells also express Bmi1, which supports self-renewal of stem cells. Lung adenomas spontaneously develop in aging Runx3 þ /À mice (B18 months after birth) and invariably exhibit reduced levels of Runx3. As K-ras mutations are very rare in these adenomas, Runx3 þ /À mice provide an animal model for lung tumorigenesis that recapitulates the preneoplastic stage of human lung adenocarcinoma development, which is independent of K-Ras mutation. We conclude that Runx3 is essential for lung epithelial cell differentiation, and that downregulation of Runx3 is causally linked to the preneoplastic stage of lung adenocarcinoma.

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Embryonic mouse lung epithelial progenitor cells co-express immunohistochemical markers of diverse mature cell lineages.

Cited by 106 publications

References 1 publication

Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras

Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras

Intraepithelial T-Cell Cytotoxicity, Induced Bronchus-Associated Lymphoid Tissue, and Proliferation of Pneumocytes in Experimental Mouse Models of Influenza

Runx3 is required for the differentiation of lung epithelial cells and suppression of lung cancer

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