Characterization of Epithelial Progenitors in Normal Human Palatine Tonsils and Their HPV16 E6/E7-Induced Perturbation

Sung Yoon Catherine Kang; Nagarajan Kannan; Lewei Zhang; Victor Martinez; Miriam P. Rosin; Connie J. Eaves

doi:10.1016/j.stemcr.2015.09.020

Characterization of Epithelial Progenitors in Normal Human Palatine Tonsils and Their HPV16 E6/E7-Induced Perturbation

Sung Yoon Catherine Kang, Nagarajan Kannan, Lewei Zhang, Victor Martinez, Miriam P. Rosin, Connie J. Eaves

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

17 Citas (Scopus)

Resumen

Human palatine tonsils are oropharyngeal lymphoid tissues containing multiple invaginations (crypts) in which the continuity of the outer surface epithelium is disrupted and the isolated epithelial cells intermingle with other cell types. We now show that primitive epithelial cells detectable in vitro in 2D colony assays and in a 3D culture system are CD44⁺NGFR⁺ and present in both surface and crypt regions. Transcriptome analysis indicated a high similarity between CD44⁺NGFR⁺ cells in both regions, although those isolated from the crypt contained a higher proportion of the most primitive (holo)clonogenic cells. Lentiviral transduction of CD44⁺NGFR⁺ cells from both regions with human papillomavirus 16-encoded E6/E7 prolonged their growth in 2D cultures and caused aberrant differentiation in 3D cultures. Our findings therefore reveal a shared, site-independent, hierarchical organization, differentiation potential, and transcriptional profile of normal human tonsillar epithelial progenitor cells. They also introduce a new model for investigating the mechanisms of their transformation.

Idioma original	English
Páginas (desde-hasta)	1210-1225
Número de páginas	16
Publicación	Stem Cell Reports
Volumen	5
N.º	6
DOI	https://doi.org/10.1016/j.stemcr.2015.09.020
Estado	Published - dic. 8 2015
Publicado de forma externa	Sí

Nota bibliográfica

Funding Information:
The authors thank the surgeons, pathologists, and technologists associated with the THINC study (HPV in Tonsils: Natural History of Infection and Role in Oral Cancers): Drs. K. Berean, R. O’Connor, M.J. Dickson, S. Durham, P. Lee, P. Mick, and D. Mintz; the technologists S. Ramji and M. Lok for assistance with obtaining tonsillectomy samples; D. Ko and W. Xu for assistance with flow cytometry (Flow Cytometry Facility, Terry Fox Laboratory); I. Sun for excellent technical support; and M. Hale and G. Edin for assistance with the production of lentivirus containing HPV16-E6/E7. N.K. was supported by CBCF-BC/Yukon and MITACS Elevate postdoctoral fellowships. This work was supported by grants from the Canadian Cancer Society Research Institute (to M.P.R) and the Canadian Cancer Research Society (to C.J.E.).

Publisher Copyright:
© 2015 The Authors.

ASJC Scopus Subject Areas

Biochemistry
Genetics
Developmental Biology
Cell Biology

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10.1016/j.stemcr.2015.09.020

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title = "Characterization of Epithelial Progenitors in Normal Human Palatine Tonsils and Their HPV16 E6/E7-Induced Perturbation",

abstract = "Human palatine tonsils are oropharyngeal lymphoid tissues containing multiple invaginations (crypts) in which the continuity of the outer surface epithelium is disrupted and the isolated epithelial cells intermingle with other cell types. We now show that primitive epithelial cells detectable in vitro in 2D colony assays and in a 3D culture system are CD44+NGFR+ and present in both surface and crypt regions. Transcriptome analysis indicated a high similarity between CD44+NGFR+ cells in both regions, although those isolated from the crypt contained a higher proportion of the most primitive (holo)clonogenic cells. Lentiviral transduction of CD44+NGFR+ cells from both regions with human papillomavirus 16-encoded E6/E7 prolonged their growth in 2D cultures and caused aberrant differentiation in 3D cultures. Our findings therefore reveal a shared, site-independent, hierarchical organization, differentiation potential, and transcriptional profile of normal human tonsillar epithelial progenitor cells. They also introduce a new model for investigating the mechanisms of their transformation.",

author = "Kang, {Sung Yoon Catherine} and Nagarajan Kannan and Lewei Zhang and Victor Martinez and Rosin, {Miriam P.} and Eaves, {Connie J.}",

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AU - Martinez, Victor

AU - Rosin, Miriam P.

AU - Eaves, Connie J.

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N2 - Human palatine tonsils are oropharyngeal lymphoid tissues containing multiple invaginations (crypts) in which the continuity of the outer surface epithelium is disrupted and the isolated epithelial cells intermingle with other cell types. We now show that primitive epithelial cells detectable in vitro in 2D colony assays and in a 3D culture system are CD44+NGFR+ and present in both surface and crypt regions. Transcriptome analysis indicated a high similarity between CD44+NGFR+ cells in both regions, although those isolated from the crypt contained a higher proportion of the most primitive (holo)clonogenic cells. Lentiviral transduction of CD44+NGFR+ cells from both regions with human papillomavirus 16-encoded E6/E7 prolonged their growth in 2D cultures and caused aberrant differentiation in 3D cultures. Our findings therefore reveal a shared, site-independent, hierarchical organization, differentiation potential, and transcriptional profile of normal human tonsillar epithelial progenitor cells. They also introduce a new model for investigating the mechanisms of their transformation.

AB - Human palatine tonsils are oropharyngeal lymphoid tissues containing multiple invaginations (crypts) in which the continuity of the outer surface epithelium is disrupted and the isolated epithelial cells intermingle with other cell types. We now show that primitive epithelial cells detectable in vitro in 2D colony assays and in a 3D culture system are CD44+NGFR+ and present in both surface and crypt regions. Transcriptome analysis indicated a high similarity between CD44+NGFR+ cells in both regions, although those isolated from the crypt contained a higher proportion of the most primitive (holo)clonogenic cells. Lentiviral transduction of CD44+NGFR+ cells from both regions with human papillomavirus 16-encoded E6/E7 prolonged their growth in 2D cultures and caused aberrant differentiation in 3D cultures. Our findings therefore reveal a shared, site-independent, hierarchical organization, differentiation potential, and transcriptional profile of normal human tonsillar epithelial progenitor cells. They also introduce a new model for investigating the mechanisms of their transformation.

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Characterization of Epithelial Progenitors in Normal Human Palatine Tonsils and Their HPV16 E6/E7-Induced Perturbation

Resumen

Nota bibliográfica

ASJC Scopus Subject Areas

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