Cell Stem Cell
Volume 29, Issue 8, 4 August 2022, Pages 1262-1272.e5
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Short Article
Lymphangiocrine signals are required for proper intestinal repair after cytotoxic injury

https://doi.org/10.1016/j.stem.2022.07.007Get rights and content
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Highlights

  • Intestinal crypts are in proximity to lymphatics, which express Rspo3

  • Intestinal recovery is impaired in lymphatic Rspo3 knockout mice after 5FU injury

  • Lymphatic Rspo3 knockout mice have decreased progenitor cells after 5FU injury

  • Lymphatic Rspo3 knockout mice have reduced mucus production after 5FU injury

Summary

The intestinal epithelium undergoes continuous renewal and has an exceptional capacity to regenerate after injury. Maintenance and proliferation of intestinal stem cells (ISCs) are regulated by their surrounding niche, largely through Wnt signaling. However, it remains unclear which niche cells produce signals during different injury states, and the role of endothelial cells (ECs) as a component of the ISC niche during homeostasis and after injury has been underappreciated. Here, we show that lymphatic endothelial cells (LECs) reside in proximity to crypt epithelial cells and secrete molecules that support epithelial renewal and repair. LECs are an essential source of Wnt signaling in the small intestine, as loss of LEC-derived Rspo3 leads to a lower number of stem and progenitor cells and hinders recovery after cytotoxic injury. Together, our findings identify LECs as an essential niche component for optimal intestinal recovery after cytotoxic injury.

Keywords

lymphatics
intestine
stem cells
Rspo3
endothelial
lymphangiocrine
regeneration
Sca1
mucus

Data availability

All scRNAseq data have been deposited on the Gene Expression Omnibus (GEO) and can be viewed under accession number GSE198469. This manuscript did not generate any new code. Any additional information required to reanalyze the data reported in this work is available from the lead contact upon request.

Cited by (0)

6

These authors contributed equally

7

Lead contact