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Lung Cell Lineage Mapping May Reveal Lung Renewal Strategies

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A pair of studies have delved into lung cell development, or rather re-development, uncovering clues to how lung tissue maintains itself or recovers from injury and disease. Both studies focused on mesenchymal cells, which are generally thought to play a supportive role in maintaining lung structure. These cells, it turns out, help manage the regeneration of lung tissue. They keep lung cell subpopulations in proper balance—or not, if, for example, they generate an excess of scar tissue while failing to produce sufficient numbers of functional cells.

One of the studies stratified lung mesenchymal subsets by using single-cell and population-based RNA sequencing. These techniques, deployed by scientists based at the University of Pennsylvania School of Medicine, made it possible to identify five distinct cell types in the mouse lung. Focusing on two of the five cell types, the scientists found that “each mesenchymal lineage has a distinct spatial address and transcriptional profile leading to unique niche regulatory functions.”

Details of this work, which helped the scientists produce a spatial and transcriptional map of the lung mesenchyme, appeared September 7 in the journal Cell, in an article entitled, “Distinct Mesenchymal Lineages and Niches Promote Epithelial Self-Renewal and Myofibrogenesis in the Lung.” In this article, the University of Pennsylvania team described how it analyzed secreted molecules and surface cell receptors from the cells of interest, and compared this information to databases of known secreted molecules and receptors on adjacent cells.

“The mesenchymal alveolar niche cell is WNT responsive, expresses Pdgfrα, and is critical for alveolar epithelial cell growth and self-renewal,” the article’s authors detailed. “In contrast, the Axin2+ myofibrogenic progenitor cell preferentially generates pathologically deleterious myofibroblasts after injury. Analysis of the secretome and receptome of the alveolar niche reveals functional pathways that mediate growth and self-renewal of alveolar type 2 progenitor cells, including IL-6/Stat3, Bmp, and Fgf signaling.”

The "good" mesenchymal alveolar niche cells (MANCs) are found in niches or compartments near the alveoli to promote renewal of gas-exchange cells. They may play a key role in maintaining the alveoli during the normal life span of the adult. Dysfunction or loss of MANCs may contribute to diseases such as COPD, which involves loss of alveoli and decreased lung function. The role of the "bad" Axin2+ myofibrogenic progenitor cells (AMPs) is to form scar tissue during wound healing. However, AMPs may grow out of control, potentially leading to diseases such as IPF.

"One of the most important functions of these cells is to balance the repair and regeneration response after injury which occurs often due to the lung's continual assault from the outside environment," said Edward E. Morrisey, Ph.D., senior author of the study and a professor of cell and developmental biology and director of the Penn Center for Pulmonary Biology.

 

Source : http://www.genengnews.com/gen-news-highlights/lung-cell-lineage-mapping-may-reveal-lung-renewal-strategies/81254912