Hierarchy and plasticity in the crypt: back to the drawing board
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The prevailing concept in the field of stem cell research is that of a multipotent self-renewing cell,positioned at the origin of a hierarchical tree of branching specificities,increasing maturity and decreasing self-renewal ability.In the epithelium of the small intestine,until very recently,the supra-Paneth crypt base columnar (CBC) cell position +4(cp4) (counting from the bottom of the crypt) was widely assumed to be the preferred position of multipotent stem cells ”1,2”.Yet electron microscopy,as well as autoradiography and lineage tracing studies,supported the presence of undifferentiated ”3”,actively cycling ”4”,multipotent CBC stem cells located between Paneth cells in the crypt ”5-7”.Based on the results of expression and lineage studies with Lgr5-EGFP-IRES-CreERT2 knock-in mice and Rosa26-LacZ reporter mice,it was possible to show that multipotent CBC cells expressing the Lgr5 orphan receptor are present throughout the gastro-intestinal tract ”7”.But they are not alone.Another recent lineage study revealed the existence of multipotent,self-renewing Lgr5- CBC cells expressing the Bmi1 proto-oncogene and preferentially located above the highest Paneth cell ”8”.This discovery brought the cp4 model back under the spotlight,and subsequent expression studies revealed a partial overlap between the Lgr5+ and Bmi1+ CBC cell populations ”9”.In a recent issue of Nature,Huan Tian and colleagues now tackle the issue of their contribution to the turnover of the intestinal epithelium ”10”.
the Agence Nationale pour la RechercheANR-09-BLAN-0368-01;Institut National du CancerINCa PLBIO09-070;Association pour la Recherche Contre le CancerARC SL220110603456