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Dual SMAD Signaling Inhibition Enables Long-Term Expansion of Diverse Epithelial Basal Cells
Open accessAbstract
SUMMARY Functional modeling of many adult epithelia is limited by the difficulty of maintaining relevant stem cell populations in culture. Here, we show that dual inhibition of SMAD signaling pathways enables robust expansion of primary epithelial basal cell populations. We found that TGFβ/BMP/SMAD pathway signaling is strongly activated in luminal and suprabasal cells of several epithelia, but suppressed in p63+ basal cells. In airway epithelium, SMAD signaling promotes differentiation, and its inhibition leads to stem cell hyperplasia. Using dual SMAD inhibition in a feeder-free culture system we were able to expand airway basal stem cells from multiple species. Expanded cells can produce functional airway epithelium that is physiologically responsive to clinically relevant drugs such as CFTR modulators. This approach is effective for clonal expansion of single human cells and for basal cell populations from epithelial tissues from all three germ layers, and may therefore be broadly applicable for modeling of epithelia.
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Metadata
- Authors
- Mou, H., Vinarsky, V., Tata, P. R., Brazauskas, K., Choi, S. H., Crooke, A. K., Zhang, B., Solomon, G. M., Turner, B., Bihler, H., Harrington, J., Lapey, A., Channick, C., Keyes, C., Freund, A., Artandi, S., Mense, M., Rowe, S., Engelhardt, J. F., Hsu, Y.-C., & Rajagopal, J.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 19
- Issue
- 2
- Pages
- 217-231
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2421964473
- Cited by
- 382
- References
- 40
- FWCI
- 14.90
- Type
- journal article
- Language
- en
- Open access
- bronze
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