Endogenous lung stem cells and contribution to disease

Snyder, Joshua C.; Teisanu, RM; Stripp, Barry R.

doi:10.1002/path.2473

Cited by 86 publications

(76 citation statements)

References 88 publications

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“…There is substantial evidence that the adult distal lung parenchyma, composed of bronchioles and alveoli, contains relatively quiescent epithelial cells that have proliferative and progenitor capacity (15,21,22). The current thinking is that Clara cells (or variant Clara cells with low CC10 expression) and alveolar type II cells are the main cell types with progenitor function in the distal lung parenchyma (22,23).…”

Section: Discussionmentioning

confidence: 99%

Integrin α6β4 identifies an adult distal lung epithelial population with regenerative potential in mice

Chapman

Li²,

Alexander³

et al. 2011

J. Clin. Invest.

388

257

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Laminins and their integrin receptors are implicated in epithelial cell differentiation and progenitor cell maintenance. We report here that a previously unrecognized subpopulation of mouse alveolar epithelial cells (AECs) expressing the laminin receptor α6β4, but little or no pro-surfactant C (pro-SPC), is endowed with regenerative potential. Ex vivo, this subpopulation expanded clonally as progenitors but also differentiated toward mature cell types. Integrin β4 itself was not required for AEC proliferation or differentiation. An in vivo embryonic lung organoid assay, which we believe to be novel, was used to show that purified β4 + adult AECs admixed with E14.5 lung single-cell suspensions and implanted under kidney capsules self-organized into distinct Clara cell 10-kDa secretory protein (CC10 + ) airway-like and SPC + saccular structures within 6 days. Using a bleomycin model of lung injury and an SPC-driven inducible cre to fate-map AECs, we found the majority of type II AECs in fibrotic areas were not derived from preexisting type II AECs, demonstrating that SPC -progenitor cells replenished type II AECs during repair. Our findings support the idea that there is a stable AEC progenitor population in the adult lung, provide in vivo evidence of AEC progenitor cell differentiation after parenchymal injury, and identify a strong candidate progenitor cell for maintenance of type II AECs during lung repair.

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Section: Discussionmentioning

confidence: 99%

Integrin α6β4 identifies an adult distal lung epithelial population with regenerative potential in mice

Chapman

Li²,

Alexander³

et al. 2011

J. Clin. Invest.

388

257

View full text Add to dashboard Cite

show abstract

“…In this context, stem and progenitor cells are involved in lung regeneration. They are located within the basal layer of the upper airways, within or near pulmonary neuroendocrine cell rests, at the bronchoalveolar junction, and within the epithelial surface [114][115][116]. The airway epithelium represents the first barrier to inhaled particles and pathogens and because of this, it suffers constant damages.…”

Section: Pulmonary Epithelium Injurymentioning

confidence: 99%

Perspectives of purinergic signaling in stem cell differentiation and tissue regeneration

Glaser

Cappellari

Pillat

et al. 2011

Purinergic Signalling

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Replacement of lost or dysfunctional tissues by stem cells has recently raised many investigations on therapeutic applications. Purinergic signaling has been shown to regulate proliferation, differentiation, cell death, and successful engraftment of stem cells originated from diverse origins. Adenosine triphosphate release occurs in a controlled way by exocytosis, transporters, and lysosomes or in large amounts from damaged cells, which is then subsequently degraded into adenosine. Paracrine and autocrine mechanisms induced by immune responses present critical factors for the success of stem cell therapy. While P1 receptors generally exert beneficial effects including anti-inflammatory activity, P2 receptor-mediated actions depend on the subtype of stimulated receptors and localization of tissue repair. Pro-inflammatory actions and excitatory tissue damages mainly result from P2X7 receptor activation, while other purinergic receptor subtypes participate in proliferation and differentiation, thereby providing adequate niches for stem cell engraftment and novel mechanisms for cell therapy and endogenous tissue repair. Therapeutic applications based on regulation of purinergic signaling are foreseen for kidney and heart muscle regeneration, Clara-like cell replacement for pulmonary and bronchial epithelial cells as well as for induction of neurogenesis in case of neurodegenerative diseases.

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“…The existence of stem cells has been demonstrated in various adult tissues including brain, bone marrow and peripheral blood, muscle, skin, breast, lung, kidney, liver, pancreas and thyroid gland [96][97][98][99][100][101][102][103][104][105][106][107][108]. However, genes that contribute to the stem cell phenotype and cell differentiation still need to be elucidated.…”

Section: Expression Of P63mentioning

confidence: 99%

The role of P63 in cancer, stem cells and cancer stem cells

Nekulova

Holcakova

Coates

et al. 2011

Cellular and Molecular Biology Letters

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The transcription factor p63 has important functions in tumorigenesis, epidermal differentiation and stem cell self-renewal. The TP63 gene encodes multiple protein isoforms that have different or even antagonistic roles in these processes. The balance of p63 isoforms, together with the presence or absence of the other p53 family members, p73 and p53, has a striking biological impact. There is increasing evidence that interactions between p53-family members, whether cooperative or antagonistic, are involved in various cell processes. This review summarizes the current understanding of the role of p63 in tumorigenesis, metastasis, cell migration and senescence. In particular, recent data indicate important roles in adult stem cell and cancer stem cell regulation and in the response of cancer cells to therapy.

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Endogenous lung stem cells and contribution to disease

Cited by 86 publications

References 88 publications

Integrin α6β4 identifies an adult distal lung epithelial population with regenerative potential in mice

Integrin α6β4 identifies an adult distal lung epithelial population with regenerative potential in mice

Perspectives of purinergic signaling in stem cell differentiation and tissue regeneration

The role of P63 in cancer, stem cells and cancer stem cells

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