Human-Specific Organization of Proliferation and Stemness in Squamous Epithelia : A Comparative Study to Elucidate Differences in Stem Cell Organization
department or school: Dentistry, Faculty of
department or school: Non UBC
department or school: Oral Biological and Medical Sciences (OBMS), Department of
data provider: DSpace
identifier citation: International Journal of Molecular Sciences 26 (7): 3144 (2025)
creator: Harris, Ashlee
creator: Burnham, Kaylee
creator: Pradhyumnan, Ram
creator: Jaishankar, Arthi
creator: Häkkinen, Lari
creator: Góngora-Rosero, Rafael E.
creator: Piazza, Yelena
creator: Andl, Claudia D.
creator: Andl, Thomas
issued: 2025-05-09T14:37:33Z
issued: 2025-03-28
description: The mechanisms that influence human longevity are complex and operate on cellular, tissue, and organismal levels. To better understand the tissue-level mechanisms, we compared the organization of cell proliferation, differentiation, and cytoprotective protein expression in the squamous epithelium of the esophagus between mammals with varying lifespans. Humans are the only species with a quiescent basal stem cell layer that is distinctly physically separated from parabasal transit-amplifying cells. In addition to these stark differences in the organization of proliferation, human squamous epithelial stem cells express DNA repair-related markers, such as MECP2 and XPC, which are absent or low in mouse basal cells. Furthermore, we investigated whether the transition from basal to suprabasal is different between species. In humans, the parabasal cells seem to originate from cells detaching from the basement membrane, and these can already begin to proliferate while delaminating. In most other species, delaminating cells have been rare or their proliferation rate is different from that of their human counterparts, indicating an alternative mode of how stem cells maintain the tissue. In humans, the combination of an elevated cytoprotective signature and novel tissue organization may enhance resistance to aging and prevent cancer. Our results point to enhanced cellular cytoprotection and a tissue architecture which separates stemness and proliferation. These are both potential factors contributing to the increased fitness of human squamous epithelia to support longevity by suppressing tumorigenesis. However, the organization of canine oral mucosa shows some similarities to that of human tissue and may provide a useful model to understand the relationship between tissue architecture, gene expression regulation, tumor suppression, and longevity.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/91078
note: Academic Editor: Nicola AlessioReceived: 17 February 2025Revised: 19 March 2025Accepted: 26 March 2025Published: 28 March 2025Citation: Harris, A.; Burnham, K.;Pradhyumnan, R.; Jaishankar, A.;Häkkinen, L.; Góngora-Rosero, R.E.;Piazza, Y.; Andl, C.D.; Andl, T.Human-Specific Organization ofProliferation and Stemness inSquamous Epithelia: A ComparativeStudy to Elucidate Differences in StemCell Organization. Int. J. Mol. Sci. 2025,26, 3144. https://doi.org/10.3390/ijms26073144Copyright: © 2025 by the authors.Licensee MDPI, Basel, Switzerland.This article is an open access articledistributed under the terms andconditions of the Creative CommonsAttribution (CC BY) license(https://creativecommons.org/licenses/by/4.0/).ArticleHuman-Specific Organization of Proliferation and Stemness inSquamous Epithelia: A Comparative Study to ElucidateDifferences in Stem Cell OrganizationAshlee Harris 1, Kaylee Burnham 1, Ram Pradhyumnan 1, Arthi Jaishankar 1, Lari Häkkinen 2 ,Rafael E. Góngora-Rosero 1 , Yelena Piazza 3, Claudia D. Andl 1 and Thomas Andl 1,*1 Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32826, USA;burnhamkb@gmail.com (K.B.); ra370988@ucf.edu (R.P.); euraffa@gmail.com (R.E.G.-R.)2 Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia,Vancouver, BC V6T 1Z1, Canada; lhakkine@dentistry.ubc.ca3 College of Medicine, University of Central Florida, Orlando, FL 32827, USA* Correspondence: thomas.andl@ucf.eduAbstract: The mechanisms that influence human longevity are complex and operate oncellular, tissue, and organismal levels. To better understand the tissue-level mechanisms,we compared the organization of cell proliferation, differentiation, and cytoprotectiveprotein expression in the squamous epithelium of the esophagus between mammals withvarying lifespans. Humans are the only species with a quiescent basal stem cell layer thatis distinctly physically separated from parabasal transit-amplif…
has type: Article
is shown at: 10.14288/1.0448831
language: eng
peer review status: Reviewed
provider: Vancouver : University of British Columbia Library
publisher: Multidisciplinary Digital Publishing Institute
publisher DOI: 10.3390/ijms26073144
rights: CC BY 4.0
rights URI: https://creativecommons.org/licenses/by/4.0/
scholar level: Faculty
scholar level: Researcher
subject: squamous epithelial biology
subject: esophageal stem cells
subject: spatial biology
subject: multiplex immunofluorescence
subject: comparative biology
subject: MECP2
subject: XPC
type: Text
identifier URI: http://hdl.handle.net/2429/91078