
A distinct lineage of quiescent intestinal stem cells, independent of the Lgr5-positive crypt base columnar cells, contributes to epithelial regeneration following injury.


coremsg

Collagenase/dispase treatment of intestinal tissue from adult mice generates cells growing in matrigel as immortal cystic spheroids in addition to differentiated organoids. Contrary to classical EDTA-derived organoids, these spheroids display poor intestinal differentiation and are independent of Rspondin/Noggin/EGF for growth. Their transcriptome resembles strikingly that of fetal intestinal spheroids, with downregulation of crypt base columnar cell (CBC) markers (Lgr5, Ascl2, Smoc2, Olfm4). In addition, they display upregulation of inflammatory and mesenchymal genetic programs, together with robust expression of YAP target genes. Lineage tracing, cell-sorting and single cell RNA sequencing experiments demonstrate that adult spheroid-generating cells belong to a hitherto undescribed developmental lineage, independent of Lgr5+ve CBCs, and are involved in regeneration of the epithelium following CBC ablation.

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### Competing Interest Statement

The authors have declared no competing interest.

 [1]: pending:yes

An Lgr5-independent developmental lineage is involved in mouse intestinal regeneration

identification-of-a-novel-lgr5-independent-intestinal-lineage-involved-in-epithelial-regeneration


Identification of a Novel Lgr5-Independent Intestinal Lineage Involved in Epithelial Regeneration
