RT Journal Article SR Electronic T1 An Lgr5-independent developmental lineage is involved in mouse intestinal regeneration JF bioRxiv FD Cold Spring Harbor Laboratory SP 2024.03.11.584399 DO 10.1101/2024.03.11.584399 A1 Marefati, Maryam A1 Fernandez-Vallone, Valeria A1 Leprovots, Morgane A1 Vasile, Gabriella A1 Libert, Frédérick A1 Lefort, Anne A1 Dinsart, Gilles A1 Weber, Achim A1 Jetzer, Jasna A1 Garcia, Marie-Isabelle A1 Vassart, Gilbert YR 2024 UL http://biorxiv.org/content/early/2024/08/06/2024.03.11.584399.abstract AB Collagenase/dispase treatment of intestinal tissue from adult mice generates cells growing in matrigel as stably replatable 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. Competing Interest StatementThe authors have declared no competing interest.