Lymphangiocrine signals are required for proper intestinal repair after cytotoxic injury

Brisa Palikuqi; Jérémie Rispal; Efren A Reyes; Dedeepya Vaka; Dario Boffelli; Ophir Klein

doi:10.1016/j.stem.2022.07.007

Lymphangiocrine signals are required for proper intestinal repair after cytotoxic injury

Cell Stem Cell. 2022 Aug 4;29(8):1262-1272.e5. doi: 10.1016/j.stem.2022.07.007.

Authors

Brisa Palikuqi¹, Jérémie Rispal¹, Efren A Reyes², Dedeepya Vaka³, Dario Boffelli⁴, Ophir Klein⁵

Affiliations

¹ Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
² Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Pharmaceutical Chemistry and TETRAD Program, University of California, San Francisco, San Francisco, CA, USA.
³ Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94158, USA.
⁴ Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
⁵ Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA 94143, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Electronic address: ophir.klein@ucsf.edu.

Abstract

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: Rspo3; Sca1; endothelial; intestine; lymphangiocrine; lymphatics; mucus; regeneration; stem cells.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Cell Proliferation
Endothelial Cells*
Epithelial Cells
Intestinal Mucosa
Intestines*
Stem Cells

Abstract

Publication types

MeSH terms

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