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

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

    Research output: Contribution to journalArticle

    10 Citations (Scopus)

    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

    Fingerprint

    Intestines
    Stem Cells
    Population
    Hematopoietic System
    Intestinal Mucosa
    Genes
    Health

    ASJC Scopus subject areas

    • Physiology

    Cite this

    Defining a stem cell hierarchy in the intestine : markers, caveats and controversies. / Smith, Nicholas R.; Gallagher, Alexandra C.; Wong, Melissa.

    In: Journal of Physiology, Vol. 594, No. 17, 01.09.2016, p. 4781-4790.

    Research output: Contribution to journalArticle

    Smith, Nicholas R. ; Gallagher, Alexandra C. ; Wong, Melissa. / Defining a stem cell hierarchy in the intestine : markers, caveats and controversies. In: Journal of Physiology. 2016 ; Vol. 594, No. 17. pp. 4781-4790.
    @article{896f7c1a6af04c5a94a44e6921b02ad8,
    title = "Defining a stem cell hierarchy in the intestine: markers, caveats and controversies",
    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.).",
    author = "Smith, {Nicholas R.} and Gallagher, {Alexandra C.} and Melissa Wong",
    year = "2016",
    month = "9",
    day = "1",
    doi = "10.1113/JP271651",
    language = "English (US)",
    volume = "594",
    pages = "4781--4790",
    journal = "Journal of Physiology",
    issn = "0022-3751",
    publisher = "Wiley-Blackwell",
    number = "17",

    }

    TY - JOUR

    T1 - Defining a stem cell hierarchy in the intestine

    T2 - markers, caveats and controversies

    AU - Smith, Nicholas R.

    AU - Gallagher, Alexandra C.

    AU - Wong, Melissa

    PY - 2016/9/1

    Y1 - 2016/9/1

    N2 - 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.).

    AB - 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.).

    UR - http://www.scopus.com/inward/record.url?scp=84986257298&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=84986257298&partnerID=8YFLogxK

    U2 - 10.1113/JP271651

    DO - 10.1113/JP271651

    M3 - Article

    C2 - 26864260

    AN - SCOPUS:84986257298

    VL - 594

    SP - 4781

    EP - 4790

    JO - Journal of Physiology

    JF - Journal of Physiology

    SN - 0022-3751

    IS - 17

    ER -