Lineage Tracing of FOXL1+ Cells in the Tunica Muscularis Suggests Mutual Origin for Telocytes and Smooth Muscle Cells.

Moriya Shushan,Michal Shoshkes-Carmel

doi:10.3390/life12020176

Moriya Shushan, Michal Shoshkes-Carmel

Open Access

https://doi.org/10.3390/life12020176

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Journal: Life (Basel, Switzerland)	Publication Date: Jan 26, 2022
Citations: 1	License type: CC BY 4.0

Affiliation: Hebrew University of Jerusalem

Abstract

We recently identified a FOXL1+ intestinal subepithelial network of telocytes (TCs) without which epithelial stem and progenitor cells cannot proliferate and support regeneration. In addition to FOXL1 lineage cell distribution along the intestinal epithelium, we also observed their presence within the muscle layers. Here, we characterized FOXL1+ lineage cells along the muscle layers of the duodenum in order to understand their progeny and relation to interstitial Cajal cells (ICCs), smooth muscle cells (SMCs) and the previously reported PDGFRa+ TCs. Using a FOXL1-Cre transgenic line in conjunction with genetic lineage labeling using the Rosa26-mTmG allele, in which Cre-marked cells produce a membrane-targeted version of green fluorescent protein (GFP), we found that within the muscle layers FOXL1 lineage GFP+ cells had two main progeny; (i) elongated multinucleated SMA+ SMCs, intermingled in parallel or perpendicular to muscle fibers. (ii) TCs displaying small cell body with multiple cell processes, expressing PDGFRa and CD34. These findings may suggest a mutual origin for TCs and SMCs.

Highlights

Muscularis Suggests Mutual OriginThe intestine is an outstanding model with which to study cellular coordination and cooperation and how they are regulated to achieve functional tissue
Using a FOXL1-Cre transgenic line in conjunction with genetic lineage labeling using the Rosa26-mTmG allele [3], in which Cre-marked cells produce a membrane targeted version of green fluorescent protein (GFP), we unexpectedly found that FOXL1-expressing cells belong to a novel type of mesenchymal cells called telocytes (TCs) that form a continuous comprehensive threedimensional network of contact with the entire intestinal epithelium, from the crypt base to the tip of the villi
We used a transgenic reporter mouse in which FOXL1 Cre drives the expression of a membrane-tag GFP in order to understand the identity of FOXL1 lineage cells and their relations to interstitial Cajal cells (ICCs), smooth muscle cells (SMCs) and PDGFRa+ CD34+ TCs

Summary

Introduction

Muscularis Suggests Mutual OriginThe intestine is an outstanding model with which to study cellular coordination and cooperation and how they are regulated to achieve functional tissue. In searching for the source of cells which provide the signals required for epithelial functional support, we identified mesenchymal cells expressing the transcription factor FOXL1 as an important source of Wnt proteins without which intestinal stem and progenitor cells cannot proliferate and support regeneration [1,2]. Using a FOXL1-Cre transgenic line in conjunction with genetic lineage labeling using the Rosa26-mTmG allele [3], in which Cre-marked cells produce a membrane targeted version of green fluorescent protein (GFP), we unexpectedly found that FOXL1-expressing cells belong to a novel type of mesenchymal cells called telocytes (TCs) that form a continuous comprehensive threedimensional network of contact with the entire intestinal epithelium, from the crypt base to the tip of the villi. In support of our work, recent studies from different research groups used diverse markers to label TCs and demonstrated their importance as a critical stem cell niche component that supports intestinal crypts [4,5,6]

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