Lymphatics and fibroblasts support intestinal stem cells in homeostasis and injury

Norihiro Goto; Saori Goto; Shinya Imada; Sahar Hosseini; Vikram Deshpande; Ömer H Yilmaz

doi:10.1016/j.stem.2022.06.013

Lymphatics and fibroblasts support intestinal stem cells in homeostasis and injury

Cell Stem Cell. 2022 Aug 4;29(8):1246-1261.e6. doi: 10.1016/j.stem.2022.06.013.

Authors

Norihiro Goto¹, Saori Goto², Shinya Imada², Sahar Hosseini³, Vikram Deshpande³, Ömer H Yilmaz⁴

Affiliations

¹ Department of Biology, The David H. Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: ngoto@mit.edu.
² Department of Biology, The David H. Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
³ Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
⁴ Department of Biology, The David H. Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Electronic address: ohyilmaz@mit.edu.

Abstract

Lgr5⁺ intestinal stem cells (ISCs) depend on niche factors for their proper function. However, the source of these ISC niche factors and how they support ISCs in vivo remain controversial. Here, we report that ISCs depend on lymphatic endothelial cells (LECs) and RSPO3⁺GREM1⁺ fibroblasts (RGFs). In the intestine and colon, LECs are surrounded by RGFs and are located near ISCs at the crypt base. Both LECs and RGFs provide the critical ISC niche factor RSPO3 to support ISCs, where RSPO3 loss in both cell types drastically compromises ISC numbers, villi length, and repair after injury. In response to injury, LEC and RGF numbers expand and produce greater amounts of RSPO3 and other growth/angiocrine factors to foster intestinal repair. We propose that LECs represent a novel niche component for ISCs, which together with RGFs serve as the major in vivo RSPO3 source for ISCs in homeostasis and injury-mediated regeneration.

Keywords: Lgr5; RSPO3; fibroblast; intestinal stem cell; lymphatic endothelial cell.

Publication types

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

MeSH terms

Endothelial Cells*
Fibroblasts
Homeostasis
Intestinal Mucosa / metabolism
Intestines
Stem Cells* / metabolism

Abstract

Publication types

MeSH terms

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