Wnt-responsive stem cell fates in the oral mucosa

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Abstract

Summary Epithelia of the oral cavity exhibit variations in morphologies and turnover rates. Are these differences related to environment or to region-specific stem cell populations? A lineage-tracing strategy allowed visualization of Wnt-responsive cells, and their progeny, in the hard and soft palates. In both anatomic locations, Wnt-responsive basal cells self-renewed and gave rise to supra-basal cells. Palatal injuries triggered an enlargement of this population, and their descendants were responsible for wound re-epithelialization. Compared with the hard palate, soft palate stem cells exhibited an earlier, more robust burst in proliferation, culminating in significantly faster repair. Thereafter, excess Wnt-responsive basal cells were removed, and stem cell numbers were restored back to homeostatic level. Thus, we uncovered a stem cell population in oral mucosa, and its relative abundance is correlate with the rate of oral wound healing. Besides the activation during injury, an endogenous mechanism exists to constrain the stem cell pool after repair.

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Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions.

Cristian Tomasetti, Bert Vogelstein (2015)

Some tissue types give rise to human cancers millions of times more often than other tissue types. Although this has been recognized for more than a century, it has never been explained. Here, we show that the lifetime risk of cancers of many different types is strongly correlated (0.81) with the total number of divisions of the normal self-renewing cells maintaining that tissue's homeostasis. These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to "bad luck," that is, random mutations arising during DNA replication in normal, noncancerous stem cells. This is important not only for understanding the disease but also for designing strategies to limit the mortality it causes. Copyright © 2015, American Association for the Advancement of Science.

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Mechanical forces direct stem cell behaviour in development and regeneration

David Mooney, Kyle Vining (2017)

Stem cells and their local microenvironment, or niche, communicate through mechanical cues to regulate cell fate and cell behaviour and to guide developmental processes. During embryonic development, mechanical forces are involved in patterning and organogenesis. The physical environment of pluripotent stem cells regulates their self-renewal and differentiation. Mechanical and physical cues are also important in adult tissues, where adult stem cells require physical interactions with the extracellular matrix to maintain their potency. In vitro, synthetic models of the stem cell niche can be used to precisely control and manipulate the biophysical and biochemical properties of the stem cell microenvironment and to examine how the mode and magnitude of mechanical cues, such as matrix stiffness or applied forces, direct stem cell differentiation and function. Fundamental insights into the mechanobiology of stem cells also inform the design of artificial niches to support stem cells for regenerative therapies.

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The Hippo pathway effectors TAZ and YAP in development, homeostasis and disease.

Xaralabos Varelas (2014)

Studies over the past 20 years have defined the Hippo signaling pathway as a major regulator of tissue growth and organ size. Diverse roles for the Hippo pathway have emerged, the majority of which in vertebrates are determined by the transcriptional regulators TAZ and YAP (TAZ/YAP). Key processes regulated by TAZ/YAP include the control of cell proliferation, apoptosis, movement and fate. Accurate control of the levels and localization of these factors is thus essential for early developmental events, as well as for tissue homeostasis, repair and regeneration. Recent studies have revealed that TAZ/YAP activity is regulated by mechanical and cytoskeletal cues as well as by various extracellular factors. Here, I provide an overview of these and other regulatory mechanisms and outline important developmental processes controlled by TAZ and YAP.