TBX2-positive cells represent a multi-potent mesenchymal progenitor pool in the developing lung

Autor: Vincent M. Christoffels, Timo H. Lüdtke, Mark-Oliver Trowe, Irina Wojahn, Andreas Kispert
Přispěvatelé: Medical Biology, ACS - Heart failure & arrhythmias, Amsterdam Reproduction & Development (AR&D)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Respiratory Research, Vol 20, Iss 1, Pp 1-14 (2019)
Respiratory Research
Respiratory research, 20(1):292. BioMed Central
ISSN: 1465-9921
Popis: BackgroundIn the embryonic mammalian lung, mesenchymal cells act both as a signaling center for epithelial proliferation, differentiation and morphogenesis as well as a source for a multitude of differentiated cell types that support the structure of the developing and mature organ. Whether the embryonic pulmonary mesenchyme is a homogenous precursor pool and how it diversifies into different cell lineages is poorly understood. We have previously shown that the T-box transcription factor geneTbx2is expressed in the pulmonary mesenchyme of the developing murine lung and is required therein to maintain branching morphogenesis.MethodsWe determined Tbx2/TBX2 expression in the developing murine lung by in situ hybridization and immunofluorescence analyses. We used a genetic lineage tracing approach with aCreline under the control of endogenousTbx2control elements (Tbx2cre), and theR26mTmGreporter line to trace TBX2-positive cells in the murine lung. We determined the fate of the TBX2 lineage by co-immunofluorescence analysis of the GFP reporter and differentiation markers in normal murine lungs and in lungs lacking or overexpressing TBX2 in the pulmonary mesenchyme.ResultsWe show that TBX2 is strongly expressed in mesenchymal progenitors in the developing murine lung. In differentiated smooth muscle cells and in fibroblasts, expression of TBX2 is still widespread but strongly reduced. In mesothelial and endothelial cells expression is more variable and scattered. All fetal smooth muscle cells, endothelial cells and fibroblasts derive from TBX2+progenitors, whereas half of the mesothelial cells have a different descent. The fate of TBX2-expressing cells is not changed inTbx2-deficient and inTBX2-constitutively overexpressing mice but the distribution and abundance of endothelial and smooth muscle cells is changed in the overexpression condition.ConclusionThe fate of pulmonary mesenchymal progenitors is largely independent of TBX2. Nevertheless, a successive and precisely timed downregulation of TBX2 is necessary to allow proper differentiation and functionality of bronchial smooth muscle cells and to limit endothelial differentiation. Our work suggests expression of TBX2 in an early pulmonary mesenchymal progenitor and supports a role of TBX2 in maintaining the precursor state of these cells.
Databáze: OpenAIRE
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