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Publication : The Tcf21 lineage constitutes the lung lipofibroblast population.

First Author  Park J Year  2019
Journal  Am J Physiol Lung Cell Mol Physiol Volume  316
Issue  5 Pages  L872-L885
PubMed ID  30675802 Mgi Jnum  J:275480
Mgi Id  MGI:6303677 Doi  10.1152/ajplung.00254.2018
Citation  Park J, et al. (2019) The Tcf21 lineage constitutes the lung lipofibroblast population. Am J Physiol Lung Cell Mol Physiol 316(5):L872-L885
abstractText  Transcription factor 21 (Tcf21) is a basic helix-loop-helix transcription factor required for mesenchymal development in several organs. Others have demonstrated that Tcf21 is expressed in embryonic lung mesenchyme and that loss of Tcf21 results in a pulmonary hypoplasia phenotype. Although recent single-cell transcriptome analysis has described multiple mesenchymal cell types in the lung, few have characterized the Tcf21 expressing population. To explore the Tcf21 mesenchymal lineage, we traced Tcf21-expressing cells during embryogenesis and in the adult. Our results showed that Tcf21 progenitor cells at embryonic day (E)11.5 generated a subpopulation of fibroblasts and lipofibroblasts and a limited number of smooth muscle cells. After E15.5, Tcf21 progenitor cells exclusively become lipofibroblasts and interstitial fibroblasts. Lipid metabolism genes were highly expressed in perinatal and adult Tcf21 lineage cells. Overexpression of Tcf21 in primary neonatal lung fibroblasts led to increases in intracellular neutral lipids, suggesting a regulatory role for Tcf21 in lipofibroblast function. Collectively, our results reveal that Tcf21 expression after E15.5 delineates the lipofibroblast and a population of interstitial fibroblasts. The Tcf21 inducible Cre mouse line provides a novel method for identifying and manipulating the lipofibroblast.
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