Defining a stem cell hierarchy in the intestine: markers, caveats and controversies

Nicholas R. Smith, Alexandra C. Gallagher, Melissa H. Wong

    Research output: Contribution to journalArticle

    11 Scopus citations

    Abstract

    The past decade has appreciated rapid advance in identifying the once elusive intestinal stem cell (ISC) populations that fuel the continual renewal of the epithelial layer. This advance was largely driven by identification of novel stem cell marker genes, revealing the existence of quiescent, slowly- and active-cycling ISC populations. However, a critical barrier for translating this knowledge to human health and disease remains elucidating the functional interplay between diverse stem cell populations. Currently, the precise hierarchical and regulatory relationships between these ISC populations are under intense scrutiny. The classical theory of a linear hierarchy, where quiescent and slowly-cycling stem cells self-renew but replenish an active-cycling population, is well established in other rapidly renewing tissues such as the haematopoietic system. Efforts to definitively establish a similar stem cell hierarchy within the intestinal epithelium have yielded conflicting results, been difficult to interpret, and suggest non-conventional alternatives to a linear hierarchy. While these new and potentially paradigm-shifting discoveries are intriguing, the field will require development of a number of critical tools, including highly specific stem cell marker genes along with more rigorous experimental methodologies, to delineate the complex cellular relationships within this dynamic organ system. (Figure presented.).

    Original languageEnglish (US)
    Pages (from-to)4781-4790
    Number of pages10
    JournalJournal of Physiology
    Volume594
    Issue number17
    DOIs
    StatePublished - Sep 1 2016

    ASJC Scopus subject areas

    • Physiology

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