Mitochondria Define Intestinal Stem Cell Differentiation Downstream of a FOXO/Notch Axis

• DOI: 10.1016/j.cmet.2020.10.005
• Publication Date: 2020-11-03T20:21:12Z
• Authors: Marlies C. Ludikh...; Maaike Meerlo; Marc Pages Gallego; Despina Xanthakis; Mar Burgaya Julià; Nguyen T.B. Nguyen; Eline C. Brombacher; Nalan Liv; Madelon M. Maurice; Ji-hye Paik; Boudewijn M.T. Bu...; Maria J. Rodrigue...
• Keywords: Cell fate determination; HES1

Differential WNT and Notch signaling regulates differentiation of Lgr5+ crypt-based columnar cells (CBCs) into intestinal cell lineages. Recently we showed that mitochondrial activity supports CBCs, while adjacent Paneth (PCs) show reduced activity. This implies CBC PCs involves a metabolic transition toward downregulation dependency. Here Forkhead box O (FoxO) transcription factors interact in determining fate. In agreement with the organoid data, Foxo1/3/4 deletion mouse intestine induces secretory differentiation. Importantly, FOXO converge on regulation fission, which turn provokes stem goblet PCs. Finally, scRNA-seq-based reconstruction trajectories role FOXO, Notch, mitochondria Together, this points at new signaling-metabolic axis highlights importance