Dataset Information

PDGFR?⁺ stromal adipocyte progenitors transition into epithelial cells during lobulo-alveologenesis in the murine mammary gland.

ABSTRACT: The mammary gland experiences substantial remodeling and regeneration during development and reproductive life, facilitated by stem cells and progenitors that act in concert with physiological stimuli. While studies have focused on deciphering regenerative cells within the parenchymal epithelium, cell lineages in the stroma that may directly contribute to epithelial biology is unknown. Here we identify, in mouse, the transition of a PDGFR?⁺ mesenchymal cell population into mammary epithelial progenitors. In addition to being adipocyte progenitors, PDGFR?⁺ cells make a de novo contribution to luminal and basal epithelia during mammary morphogenesis. In the adult, this mesenchymal lineage primarily generates luminal progenitors within lobuloalveoli during sex hormone exposure or pregnancy. We identify cell migration as a key molecular event that is activated in mesenchymal progenitors in response to epithelium-derived chemoattractant. These findings demonstrate a stromal reservoir of epithelial progenitors and provide insight into cell origins and plasticity during mammary tissue growth.

SUBMITTER: Joshi PA

PROVIDER: S-EPMC6465250 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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PDGFRα<sup>+</sup> stromal adipocyte progenitors transition into epithelial cells during lobulo-alveologenesis in the murine mammary gland.

Joshi Purna A PA Waterhouse Paul D PD Kasaian Katayoon K Fang Hui H Gulyaeva Olga O Sul Hei Sook HS Boutros Paul C PC Khokha Rama R

Nature communications 20190415 1

The mammary gland experiences substantial remodeling and regeneration during development and reproductive life, facilitated by stem cells and progenitors that act in concert with physiological stimuli. While studies have focused on deciphering regenerative cells within the parenchymal epithelium, cell lineages in the stroma that may directly contribute to epithelial biology is unknown. Here we identify, in mouse, the transition of a PDGFRα<sup>+</sup> mesenchymal cell population into mammary epi ...[more]

PMID: 30988300

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Project description:BACKGROUND:Alveologenesis is the final stage of lung development to form air-exchanging units between alveoli and blood vessels. Genetic susceptibility or hyperoxic stress to perturb this complicated process can cause abnormal enlargement of alveoli and lead to bronchopulmonary dysplasia (BPD)-associated emphysema. Platelet-derived growth factor receptor α (PDGFRα) signaling is crucial for alveolar myofibroblast (MYF) proliferation and its deficiency is associated with risk of BPD, but posttranscriptional mechanisms regulating PDGFRα synthesis during lung development remain largely unexplored. Cytoplasmic polyadenylation element-binding protein 2 (CPEB2) is a sequence-specific RNA-binding protein and translational regulator. Because CPEB2-knockout (KO) mice showed emphysematous phenotypes, we investigated how CPEB2-controlled translation affects pulmonary development and function. METHODS:Respiratory and pulmonary functions were measured by whole-body and invasive plethysmography. Histological staining and immunohistochemistry were used to analyze morphology, proliferation, apoptosis and cell densities from postnatal to adult lungs. Western blotting, RNA-immunoprecipitation, reporter assay, primary MYF culture and ectopic expression rescue were performed to demonstrate the role of CPEB2 in PDGFRα mRNA translation and MYF proliferation. RESULTS:Adult CPEB2-KO mice showed emphysema-like dysfunction. The alveolar structure in CPEB2-deficient lungs appeared normal at birth but became simplified through the alveolar stage of lung development. In CPEB2-null mice, we found reduced proliferation of MYF progenitors during alveolarization, abnormal deposition of elastin and failure of alveolar septum formation, thereby leading to enlarged pulmonary alveoli. We identified that CPEB2 promoted PDGFRα mRNA translation in MYF progenitors and this positive regulation could be disrupted by H2O2, a hyperoxia-mimetic treatment. Moreover, decreased proliferating ability in KO MYFs due to insufficient PDGFRα expression was rescued by ectopic expression of CPEB2, suggesting an important role of CPEB2 in upregulating PDGFRα signaling for pulmonary alveologenesis. CONCLUSIONS:CPEB2-controlled translation, in part through promoting PDGFRα expression, is indispensable for lung development and function. Since defective pulmonary PDGFR signaling is a key feature of human BPD, CPEB2 may be a risk factor for BPD.

Dataset Information

PDGFR?⁺ stromal adipocyte progenitors transition into epithelial cells during lobulo-alveologenesis in the murine mammary gland.

Publications

PDGFRα<sup>+</sup> stromal adipocyte progenitors transition into epithelial cells during lobulo-alveologenesis in the murine mammary gland.

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Dataset Information

PDGFR?+ stromal adipocyte progenitors transition into epithelial cells during lobulo-alveologenesis in the murine mammary gland.

Publications

PDGFRα<sup>+</sup> stromal adipocyte progenitors transition into epithelial cells during lobulo-alveologenesis in the murine mammary gland.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

PDGFR?⁺ stromal adipocyte progenitors transition into epithelial cells during lobulo-alveologenesis in the murine mammary gland.