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Dual SMAD Signaling Inhibition Enables Long-Term Expansion of Diverse Epithelial Basal Cells.

Publication ,  Journal Article
Mou, H; Vinarsky, V; Tata, PR; Brazauskas, K; Choi, SH; Crooke, AK; Zhang, B; Solomon, GM; Turner, B; Bihler, H; Harrington, J; Lapey, A ...
Published in: Cell Stem Cell
August 4, 2016

Functional modeling of many adult epithelia is limited by the difficulty in 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 find 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 signaling inhibition in a feeder-free culture system, we have been able to expand airway basal stem cells from multiple species. Expanded cells can produce functional airway epithelium physiologically responsive to clinically relevant drugs, such as CFTR modulators. This approach is effective for the clonal expansion of single human cells and for basal cell populations from epithelial tissues from all three germ layers and therefore may be broadly applicable for modeling of epithelia.

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Published In

Cell Stem Cell

DOI

EISSN

1875-9777

Publication Date

August 4, 2016

Volume

19

Issue

2

Start / End Page

217 / 231

Location

United States

Related Subject Headings

  • Telomere
  • Smad Proteins
  • Signal Transduction
  • Mucus
  • Mice, Inbred C57BL
  • Lung
  • Keratinocytes
  • Humans
  • Epithelium
  • Epithelial Cells
 

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Mou, H., Vinarsky, V., Tata, P. R., Brazauskas, K., Choi, S. H., Crooke, A. K., … Rajagopal, J. (2016). Dual SMAD Signaling Inhibition Enables Long-Term Expansion of Diverse Epithelial Basal Cells. Cell Stem Cell, 19(2), 217–231. https://doi.org/10.1016/j.stem.2016.05.012
Mou, Hongmei, Vladimir Vinarsky, Purushothama Rao Tata, Karissa Brazauskas, Soon H. Choi, Adrianne K. Crooke, Bing Zhang, et al. “Dual SMAD Signaling Inhibition Enables Long-Term Expansion of Diverse Epithelial Basal Cells.Cell Stem Cell 19, no. 2 (August 4, 2016): 217–31. https://doi.org/10.1016/j.stem.2016.05.012.
Mou H, Vinarsky V, Tata PR, Brazauskas K, Choi SH, Crooke AK, et al. Dual SMAD Signaling Inhibition Enables Long-Term Expansion of Diverse Epithelial Basal Cells. Cell Stem Cell. 2016 Aug 4;19(2):217–31.
Mou, Hongmei, et al. “Dual SMAD Signaling Inhibition Enables Long-Term Expansion of Diverse Epithelial Basal Cells.Cell Stem Cell, vol. 19, no. 2, Aug. 2016, pp. 217–31. Pubmed, doi:10.1016/j.stem.2016.05.012.
Mou H, Vinarsky V, Tata PR, Brazauskas K, Choi SH, Crooke AK, Zhang B, Solomon GM, Turner B, Bihler H, Harrington J, Lapey A, Channick C, Keyes C, Freund A, Artandi S, Mense M, Rowe S, Engelhardt JF, Hsu Y-C, Rajagopal J. Dual SMAD Signaling Inhibition Enables Long-Term Expansion of Diverse Epithelial Basal Cells. Cell Stem Cell. 2016 Aug 4;19(2):217–231.
Journal cover image

Published In

Cell Stem Cell

DOI

EISSN

1875-9777

Publication Date

August 4, 2016

Volume

19

Issue

2

Start / End Page

217 / 231

Location

United States

Related Subject Headings

  • Telomere
  • Smad Proteins
  • Signal Transduction
  • Mucus
  • Mice, Inbred C57BL
  • Lung
  • Keratinocytes
  • Humans
  • Epithelium
  • Epithelial Cells