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Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE97055 | GEO | 2018/01/08

SECONDARY ACCESSION(S): PRJNA380604

REPOSITORIES: GEO

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Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor.

Project description:Functional tissue regeneration is required for the restoration of normal organ homeostasis after severe injury. Some organs, such as the intestine, harbour active stem cells throughout homeostasis and regeneration; more quiescent organs, such as the lung, often contain facultative progenitor cells that are recruited after injury to participate in regeneration. Here we show that a Wnt-responsive alveolar epithelial progenitor (AEP) lineage within the alveolar type 2 cell population acts as a major facultative progenitor cell in the distal lung. AEPs are a stable lineage during alveolar homeostasis but expand rapidly to regenerate a large proportion of the alveolar epithelium after acute lung injury. AEPs exhibit a distinct transcriptome, epigenome and functional phenotype and respond specifically to Wnt and Fgf signalling. In contrast to other proposed lung progenitor cells, human AEPs can be directly isolated by expression of the conserved cell surface marker TM4SF1, and act as functional human alveolar epithelial progenitor cells in 3D organoids. Our results identify the AEP lineage as an evolutionarily conserved alveolar progenitor that represents a new target for human lung regeneration strategies.

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Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor [ATAC-seq]

Project description:The lung alveolus is the primary site of gas exchange in mammals. Within the alveolus, the alveolar type 2 (AT2) epithelial cell population generates surfactant to maintain alveolar structure and harbors a regenerative capacity to repair the alveolus after injury. We show that a Wnt-responsive alveolar epithelial progenitor (AEP) lineage within the AT2 cell population is critical for regenerating the alveolar niche. AEPs are a stable lineage during alveolar homeostasis but expand rapidly to regenerate a majority of the alveolar epithelium after acute lung injury. AEPs exhibit a distinct transcriptome, epigenome, and functional phenotype with specific responsiveness to Wnt and FGF signaling that modulates differentiation and self-renewal, respectively. Importantly, human AEPs (hAEPs) can be isolated and characterized through a conserved surface marker and are required for human alveolar self-renewal and differentiation using alveolar organoid assays. Together, our findings show that AEPs are an evolutionarily conserved alveolar progenitor lineage essential for regenerating the alveolar niche in the mammalian lung.

2018-01-08 | GSE97052 | GEO

Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor [mouse RNA-seq]

2018-01-08 | GSE97054 | GEO

Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor [human RNA-seq]

2018-01-08 | GSE97053 | GEO

Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor.

Project description:Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor.

| PRJNA380604 | ENA

Mst1/2-Yap in lung epithelial progenitor cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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In vivo activation of a conserved microRNA program induces robust mammalian heart regeneration