Heterogeneity within Stratified Epithelial Stem Cell Populations Maintains the Oral Mucosa in Response to Physiological Stress.,Cell Stem Cell

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Heterogeneity within Stratified Epithelial Stem Cell Populations Maintains the Oral Mucosa in Response to Physiological Stress.
Cell Stem Cell ( IF 19.8 ) Pub Date : 2019-12-05 , DOI: 10.1016/j.stem.2019.11.005
Kevin M Byrd ₁ , Natalie C Piehl ₂ , Jeet H Patel ₂ , Won Jae Huh ₃ , Inês Sequeira ₄ , Kendall J Lough ₂ , Bethany L Wagner ₂ , Pauline Marangoni ₅ , Fiona M Watt ₄ , Ophir D Klein ₅ , Robert J Coffey ₆ , Scott E Williams ₇

Affiliation

Department of Pathology & Laboratory Medicine, the University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Division of Oral & Craniofacial Health Sciences, the University of North Carolina Adams School of Dentistry, Chapel Hill, NC 27599, USA.
Department of Pathology & Laboratory Medicine, the University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Centre for Stem Cells & Regenerative Medicine, King's College London, London E1 9RT, UK.
Department of Pediatrics and Institute for Human Genetics, Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37235, USA; Department of Veterans Affairs Medical Center, Nashville, Vanderbilt University, TN 37212, USA.
Department of Pathology & Laboratory Medicine, the University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, the University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Stem cells in stratified epithelia are generally believed to adhere to a non-hierarchical single-progenitor model. Using lineage tracing and genetic label-retention assays, we show that the hard palatal epithelium of the oral cavity is unique in displaying marked proliferative heterogeneity. We identify a previously uncharacterized, infrequently-dividing stem cell population that resides within a candidate niche, the junctional zone (JZ). JZ stem cells tend to self-renew by planar symmetric divisions, respond to masticatory stresses, and promote wound healing, whereas frequently-dividing cells reside outside the JZ, preferentially renew through perpendicular asymmetric divisions, and are less responsive to injury. LRIG1 is enriched in the infrequently-dividing population in homeostasis, dynamically changes expression in response to tissue stresses, and promotes quiescence, whereas Igfbp5 preferentially labels a rapidly-growing, differentiation-prone population. These studies establish the oral mucosa as an important model system to study epithelial stem cell populations and how they respond to tissue stresses.

中文翻译：

分层上皮干细胞群内的异质性维持了对生理应激的口腔粘膜。

一般认为，分层上皮中的干细胞遵守非分层的单祖细胞模型。使用谱系追踪和遗传标记保留测定，我们显示口腔的硬pa上皮在显示明显的增殖异质性方面是独特的。我们确定驻留在候选的利基，交界区（JZ）内以前未表征的，不经常分裂的干细胞群体。JZ干细胞倾向于通过平面对称分裂自我更新，响应咀嚼压力并促进伤口愈合，而频繁分裂的细胞位于JZ外部，优先通过垂直的不对称分裂进行更新，并且对损伤的反应较弱。LRIG1丰富了动态平衡中不常见的人群，可根据组织压力动态改变表达，并促进静止，而Igfbp5优先标记快速增长且易于分化的种群。这些研究将口腔粘膜确立为研究上皮干细胞种群及其对组织应激反应的重要模型系统。

更新日期：2019-12-05

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