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Location, location, location! The reality of life for an intestinal stem cell in the crypt
Author(s) -
Walther Viola,
Graham Trevor A
Publication year - 2014
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4370
Subject(s) - stem cell , biology , crypt , microbiology and biotechnology , lgr5 , adult stem cell , cellular differentiation , population , cancer stem cell , genetics , medicine , gene , environmental health , endocrinology
The intestinal crypt has become the archetypal system to understand stem cell behaviour in vivo . Advances in lineage‐tracing technology have identified rapidly cycling stem cells at the crypt base with prominent expression of 'marker' genes such as Lgr5. Elegant quantitative analysis of lineage‐tracing data has shown that each stem cell within the crypt is in continual neutral competition with the others in order to retain its place in the niche and so prevent differentiation into a specialized lineage. Accordingly, it appears that the regulation of the stem cell pool occurs primarily at the level of the stem cell population , as a simple consequence of competition for the limited space within the niche. However, contradictory data showing that cells located away from the crypt base niche can also sometimes function as stem cells has challenged the notion that stemness is fundamentally cell‐extrinsic. Writing in Nature , Ritsma and colleagues have resolved this debate by performing in vivo live‐imaging of the crypt base. By tracking individual stem cells over time, they showed that the relative positioning of the cell within the niche stochastically regulates its fate. Stem cells located in close proximity to the crypt base were more likely to persist long‐term, but peripheral cells could sometimes move into privileged crypt‐base positions. Thus, while many cells within the crypt have stem cell potential, only cells lucky enough to reside in the 'Goldilocks zone' behave as functional stem cells in the long term. The hunt for intestinal stem cells is over: the stem cells are simply found in their niche. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.