Exploiting induced senescence in intestinal organoids to drive enteroendocrine cell expansion
The remarkable plasticity of adult stem cells within the gastrointestinal tract has been further highlighted by a recent paper from the Clevers’ group published in Cell Stem Cell this year (1). This study reports on some fundamental aspects of organoid biology that are of general interest as well as putting a focus on how differentiation is regulated in one of the remaining under-explored cell lineages—enteroendocrine cells. Enteroendocrine cells play diverse roles serving as factories for hormone secretion but as they comprise a minor fraction of cell types in the epithelium and are not easily identified under light microscopy via morphological criteria alone, there have been less studies on the molecular mechanisms that control their cell fate. It is important to note that despite the relatively low cellular abundance the intestine is arguably the largest endocrine organ in the body (2). In organoids, enteroendocrine cells also represent a relatively small fraction of the cell types present and are inherently heterogeneous so they have been challenging to study. The recent paper by Onour Basak and colleagues made use of the organoid system but instead of driving proliferation of stem/progenitor cells, they exploited the consequences of induced quiescence and revealed the expansion of enteroendocrine progenitors when the organoids were reactivated.