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Lung Stem Cell Differentiation in Mice Directed by Endothelial Cells via a BMP4-NFATc1-Thrombospondin-1 Axis
Open accessAbstract
SUMMARY Lung stem cells are instructed to produce lineage-specific progeny through unknown factors in their microenvironment. We used clonal three-dimensional (3D) co-cultures of endothelial cells and distal lung stem cells, bronchioalveolar stem cells (BASCs), to probe the instructive mechanisms. Single BASCs had bronchiolar and alveolar differentiation potential in lung endothelial cell co-cultures. Gain and loss of function experiments showed BMP4-Bmpr1a signaling triggers calcineurin/NFATc1-dependent expression of Thrombospondin-1 (Tsp1) in lung endothelial cells to drive alveolar lineage-specific BASC differentiation. Tsp1-null mice exhibited defective alveolar injury repair, confirming a crucial role for the BMP4-NFATc1-TSP1 axis in lung epithelial differentiation and regeneration in vivo. Discovery of this pathway points to methods to direct the derivation of specific lung epithelial lineages from multipotent cells. These findings elucidate a pathway that may be a critical target in lung diseases and provide new tools to understand the mechanisms of respiratory diseases at the single cell level.
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Type 2 alveolar cells are stem cells in adult lung
Barkauskas, C. E., Cronce, M. J., Rackley, C. R., Bowie, E. J., Keene, D. R., Stripp, B. R., Randell, S. H., Noble, P. W., & Hogan, B. L. M. (2013) · Journal of Clinical Investigation · doi:10.1172/jci68782 · Cited by 1,776 · cited 1×
“%) of total platelet α granule content during platelet activation (Baenziger et al., 1971; Ganguly, 1971; Lawler et al., 1978).”
BackgroundSelf-citationWright, D. E., Cheshier, S. H., Wagers, A. J., Randall, T. D., Christensen, J. L., & Weissman, I. L. (2001) · Blood · doi:10.1182/blood.v97.8.2278 · Cited by 208
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Metadata
- Authors
- Lee, J.-H., Bhang, D. H., Beede, A., Huang, T. L., Stripp, B. R., Bloch, K. D., Wagers, A. J., Tseng, Y.-H., Ryeom, S., & Kim, C. F.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 156
- Issue
- 3
- Pages
- 440-455
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2015254140
- Cited by
- 490
- References
- 2
- FWCI
- 30.29
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Lee, J.-H., Bhang, D. H., Beede, A., Huang, T. L., Stripp, B. R., Bloch, K. D., Wagers, A. J., Tseng, Y.-H., Ryeom, S., & Kim, C. F. (2014). Lung Stem Cell Differentiation in Mice Directed by Endothelial Cells via a BMP4-NFATc1-Thrombospondin-1 Axis. Cell. https://doi.org/10.1016/j.cell.2013.12.039
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