Review gut enteroendocrine cells in light of new data

[dosumis]

Background:

• gut enteroendocrine cells have classically been thought of as a diverse set of cell types each of which secretes one hormone. Recent data questions this, finding evidence for multiple hormones per cell type, a restricted number of lineage, some level of plasticity and evidence that different hormones may be expressed at different levels of maturity.

The purpose of this ticket is to review new data and evidence to decide how we should modify CL to reflect it. One possibility would be to keep classical terms as classifications and overlay a more modern understanding on top of that. More radically, we could re-organise to reflect new understanding of lineage.

Key papers to review:

• Review: https://academic.oup.com/edrv/article/41/5/bnaa018/5856764
• Gehart, Helmuth, Johan H. van Es, Karien Hamer, Joep Beumer, Kai Kretzschmar, Johanna F. Dekkers, Anne Rios, and Hans Clevers. 2019. “Identification of Enteroendocrine Regulators by Real-Time Single-Cell Differentiation Mapping.” Cell 176 (5): 1158-1173.e16. https://doi.org/10.1016/j.cell.2018.12.029.
• Hysenaj, Franc, Michael Lauber, Andrea Bast-Habersbrunner, Markus List, and Martin Klingenspor. 2024. “Single-Cell Transcriptome Analysis Reveals Secretin as a Hallmark of Human Enteroendocrine Cell Maturation.” Scientific Reports 14 (1): 13525. https://doi.org/10.1038/s41598-024-63699-0.
• Older review - includes morphology details: Latorre, R., C. Sternini, R. De Giorgio, and B. Greenwood-Van Meerveld. 2016. “Enteroendocrine Cells: A Review of Their Role in Brain-Gut Communication.” Neurogastroenterology and Motility: The Official Journal of the European Gastrointestinal Motility Society 28 (5): 620–30. https://doi.org/10.1111/nmo.12754.

[dosumis]

First impressions:

As these are rare cell types, sc transcriptomics of sorted cells are likely to give better resolution. See:

https://doi.org/10.1016/j.cell.2018.12.029.

In this case, many of the cell types we have are supported - but not S cells.

.
There is no discrete S-cell cluster - (Relevant ticket #2902)

.

This is a list of major enteroendocrine cell types in CL (not limited to gut)

'type A enteroendocrine cell'
'type D enteroendocrine cell'
'type EC enteroendocrine cell'
'type G enteroendocrine cell'
'type I enteroendocrine cell'
'type L enteroendocrine cell'
'type N enteroendocrine cell'
'type S enteroendocrine cell'
'type TG enteroendocrine cell'
'type X enteroendocrine cell'
'GIP cell'
'P enteroendocrine cell'
'P/D1 enteroendocrine cell'
'PP cell of intestine'
'PP cell'

But:

• These types are not defined in terms of single hormones, so defs may need to be tweaked.

Proposed lineage - from tracking + KO. Bold blue = genes whose K/O => enteroendocrine phenotype

[dosumis]

1. Look through definitions - if they assert single hormones, check against data and compose new defs if needed.
2. Make plan for S cells - do we keep as a class but add a warning comment or obsolete and add synonyms.