Krt19+/Lgr5- Cells Are Radioresistant Cancer-Initiating Stem Cells in the Colon and Intestine

Samuel Asfaha, Yoku Hayakawa, Ashlesha Muley, Sarah Stokes, Trevor A. Graham, Russell E. Ericksen, Christoph B. Westphalen, Johannes Von Burstin, Teresa L. Mastracci, Daniel L. Worthley, Chandan Guha, Michael Quante, Anil K. Rustgi, Timothy C. Wang

Research output: Contribution to journalArticle

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Abstract

Epithelium of the colon and intestine are renewed every 3 days. In the intestine there are at least two principal stem cell pools. The first contains rapid cycling crypt-based columnar (CBC) Lgr5+ cells, and the second is composed of slower cycling Bmi1-expressing cells at the +4 position above the crypt base. In the colon, however, the identification of Lgr5- stem cell pools has proven more challenging. Here, we demonstrate that the intermediate filament keratin-19 (Krt19) marks long-lived, radiation-resistant cells above the crypt base that generate Lgr5+ CBCs in the colon and intestine. In colorectal cancer models, Krt19+ cancer-initiating cells are also radioresistant, while Lgr5+ stem cells are radiosensitive. Moreover, Lgr5+ stem cells are dispensable in both the normal and neoplastic colonic epithelium, as ablation of Lgr5+ stem cells results in their regeneration from Krt19-expressing cells. Thus, Krt19+ stem cells are a discrete target relevant for cancer therapy.

Original languageEnglish (US)
Pages (from-to)627-638
Number of pages12
JournalCell Stem Cell
Volume16
Issue number6
DOIs
StatePublished - Jun 4 2015

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Keratin-19
Neoplastic Stem Cells
Intestines
Colon
Stem Cells
Epithelium
Intermediate Filaments
Regeneration
Colorectal Neoplasms
Neoplasms
Radiation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics

Cite this

Asfaha, S., Hayakawa, Y., Muley, A., Stokes, S., Graham, T. A., Ericksen, R. E., ... Wang, T. C. (2015). Krt19+/Lgr5- Cells Are Radioresistant Cancer-Initiating Stem Cells in the Colon and Intestine. Cell Stem Cell, 16(6), 627-638. https://doi.org/10.1016/j.stem.2015.04.013

Krt19+/Lgr5- Cells Are Radioresistant Cancer-Initiating Stem Cells in the Colon and Intestine. / Asfaha, Samuel; Hayakawa, Yoku; Muley, Ashlesha; Stokes, Sarah; Graham, Trevor A.; Ericksen, Russell E.; Westphalen, Christoph B.; Von Burstin, Johannes; Mastracci, Teresa L.; Worthley, Daniel L.; Guha, Chandan; Quante, Michael; Rustgi, Anil K.; Wang, Timothy C.

In: Cell Stem Cell, Vol. 16, No. 6, 04.06.2015, p. 627-638.

Research output: Contribution to journalArticle

Asfaha, S, Hayakawa, Y, Muley, A, Stokes, S, Graham, TA, Ericksen, RE, Westphalen, CB, Von Burstin, J, Mastracci, TL, Worthley, DL, Guha, C, Quante, M, Rustgi, AK & Wang, TC 2015, 'Krt19+/Lgr5- Cells Are Radioresistant Cancer-Initiating Stem Cells in the Colon and Intestine', Cell Stem Cell, vol. 16, no. 6, pp. 627-638. https://doi.org/10.1016/j.stem.2015.04.013
Asfaha S, Hayakawa Y, Muley A, Stokes S, Graham TA, Ericksen RE et al. Krt19+/Lgr5- Cells Are Radioresistant Cancer-Initiating Stem Cells in the Colon and Intestine. Cell Stem Cell. 2015 Jun 4;16(6):627-638. https://doi.org/10.1016/j.stem.2015.04.013
Asfaha, Samuel ; Hayakawa, Yoku ; Muley, Ashlesha ; Stokes, Sarah ; Graham, Trevor A. ; Ericksen, Russell E. ; Westphalen, Christoph B. ; Von Burstin, Johannes ; Mastracci, Teresa L. ; Worthley, Daniel L. ; Guha, Chandan ; Quante, Michael ; Rustgi, Anil K. ; Wang, Timothy C. / Krt19+/Lgr5- Cells Are Radioresistant Cancer-Initiating Stem Cells in the Colon and Intestine. In: Cell Stem Cell. 2015 ; Vol. 16, No. 6. pp. 627-638.
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