Intestinal Lymphatic Endothelial Cells Produce R-Spondin3

Ogasawara, Reiki; Hashimoto, Daigo; Kimura, Shunsuke; Hayase, Eiko; Ara, Takahide; Takahashi, Shūichirō; Ohigashi, Hiroyuki; Yoshioka, Kosuke; Tateno, Takahiro; Yokoyama, Emi; Ebata, Ko; Kondo, Takeshi; Sato, Junichi; Onozawa, Masahiro; Iwanaga, Toshihiko; Teshima, Takanori

doi:10.1038/s41598-018-29100-7

Cited by 39 publications

(30 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the intestinal epithelium is not shaped by fibroblast and telocyte-derived products alone. Intestinal endothelial cells have been recently linked to production of RSPO3 to maintain intestinal homeostasis (see Figure 2B ; Ogasawara et al, 2018 ). On the other hand, myocytes produce WNT antagonists, namely DKK3 and SFRP1 that may limit WNT signaling activation above the stem cell zone and thus induce differentiation of stem cell progeny ( McCarthy et al, 2020 ).…”

Section: More Than Stroma – the Intestinal Mesenchymementioning

confidence: 99%

The Intestinal Epithelium – Fluid Fate and Rigid Structure From Crypt Bottom to Villus Tip

Bonis

Rossell

Gehart

2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The single-layered, simple epithelium of the gastro-intestinal tract controls nutrient uptake, coordinates our metabolism and shields us from pathogens. Despite its seemingly simple architecture, the intestinal lining consists of highly distinct cell populations that are continuously renewed by the same stem cell population. The need to maintain balanced diversity of cell types in an unceasingly regenerating tissue demands intricate mechanisms of spatial or temporal cell fate control. Recent advances in single-cell sequencing, spatio-temporal profiling and organoid technology have shed new light on the intricate micro-structure of the intestinal epithelium and on the mechanisms that maintain it. This led to the discovery of unexpected plasticity, zonation along the crypt-villus axis and new mechanism of self-organization. However, not only the epithelium, but also the underlying mesenchyme is distinctly structured. Several new studies have explored the intestinal stroma with single cell resolution and unveiled important interactions with the epithelium that are crucial for intestinal function and regeneration. In this review, we will discuss these recent findings and highlight the technologies that lead to their discovery. We will examine strengths and limitations of each approach and consider the wider impact of these results on our understanding of the intestine in health and disease.

show abstract

Section: More Than Stroma – the Intestinal Mesenchymementioning

confidence: 99%

The Intestinal Epithelium – Fluid Fate and Rigid Structure From Crypt Bottom to Villus Tip

Bonis

Rossell

Gehart

2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…We found that R-Spo3 is the major molecule produced in the small intestine (10). Although it has been reported that mesenchymal cells, including telocytes, produce R-Spo3, we found that CD90 + CD31 + podoplanin + lymphatic endothelial cells are the main producers of R-Spo3 in the intestine (10,16). Importantly, both the R-Spo3 production and absolute numbers of lymphatic endothelial cells are significantly reduced in GVHD (10).…”

Section: Injury Of the Isc Nichementioning

confidence: 53%

“…R-Spo1-R-Spo4 share a similar structure, and each of these four molecules can bind to LGR4, LGR5 and LGR6 (63). We found that R-Spo3 is the major molecule produced in the small intestine (10). Although it has been reported that mesenchymal cells, including telocytes, produce R-Spo3, we found that CD90 + CD31 + podoplanin + lymphatic endothelial cells are the main producers of R-Spo3 in the intestine (10,16).…”

Section: Injury Of the Isc Nichementioning

confidence: 62%

Novel Insights Into the Mechanism of GVHD-Induced Tissue Damage

Ara

Hashimoto

2021

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

Prophylaxis for and treatment of graft-versus-host disease (GVHD) are essential for successful allogeneic hematopoietic stem cell transplantation (allo-SCT) and mainly consist of immunosuppressants such as calcineurin inhibitors. However, profound immunosuppression can lead to tumor relapse and infectious complications, which emphasizes the necessity of developing novel management strategies for GVHD. Emerging evidence has revealed that tissue-specific mechanisms maintaining tissue homeostasis and promoting tissue tolerance to combat GVHD are damaged after allo-SCT, resulting in exacerbation and treatment refractoriness of GVHD. In the gastrointestinal tract, epithelial regeneration derived from intestinal stem cells (ISCs), a microenvironment that maintains healthy gut microbiota, and physical and chemical mucosal barrier functions against pathogens are damaged by conditioning regimens and/or GVHD. The administration of growth factors for cells that maintain intestinal homeostasis, such as interleukin-22 (IL-22) for ISCs, R-spondin 1 (R-Spo1) for ISCs and Paneth cells, and interleukin-25 (IL-25) for goblet cells, mitigates murine GVHD. In this review, we summarize recent advances in the understanding of GVHD-induced tissue damage and emerging strategies for the management of GVHD.

show abstract

“…These CD34+ Gp38+ CSCs acquire the characteristics of lymphoid stromal cells and initiate lymphoid tissue genesis, as these adhesion molecules are essential for the establishment of the cell-cell contact between stromal cells and lymphocytes [51]. Noteworthy, CD45-/CD90+/CD31+ intestinal LECs in the lamina propria produce R-spondin3, which is structurally similar to the other three members of the R-spondin family which potentiate Wnt/β-catenin signalling by inhibiting the turnover of Wnt receptors [53].…”

Section: Discussionmentioning

confidence: 99%

An Immunohistochemical Study of Gastric Mucosa and Critical Review Indicate That the Subepithelial Telocytes Are Prelymphatic Endothelial Cells

et al. 2019

View full text Add to dashboard Cite

There are only a few studies regarding gut subepithelial telocytes (TCs). The telopodes, namely peculiar TCs’ prolongations described on two-dimensional cuts, are not enough to differentiate this specific cell type. Subepithelial TCs were associated with the intestinal stem niche but a proper differential diagnosis with lymphatic endothelial cells (LECs) was not performed. In this study, we will critically review studies suggesting that distinctive TCs could be positioned within the lamina propria. Additionally, we performed an immunohistochemical study of human gastric mucosa to test the expression of D2-40, the lymphatic marker, as well as that of CD31, CD34, CD44, CD117/c-kit, α-smooth muscle actin (α-SMA) and vimentin in the gastric subepithelial niche. The results support the poorly investigated anatomy of intramural gastric lymphatics, with circumferential collectors located on both sides of the muscularis mucosae (mucosal and then submucosal) and myenteric collectors in the muscularis propria. We also found superficial epithelial prelymphatic channels bordered by D2-40+ but CD31–TC-like cells. Deep epithelial lymphatic collectors drain in collectors within the lamina propria. Blood endothelial cells expressed CD31, CD34, CD44, and vimentin. Therefore, the positive diagnosis of TC for subepithelial CD34+ cells should be regarded with caution, as they could also be artefacts, resulting from the two-dimensional examination of three dimensional structures, or as LECs. Lymphatic markers should be routinely used to discriminate TCs from LECs.

show abstract

Intestinal Lymphatic Endothelial Cells Produce R-Spondin3

Cited by 39 publications

References 35 publications

The Intestinal Epithelium – Fluid Fate and Rigid Structure From Crypt Bottom to Villus Tip

The Intestinal Epithelium – Fluid Fate and Rigid Structure From Crypt Bottom to Villus Tip

Novel Insights Into the Mechanism of GVHD-Induced Tissue Damage

An Immunohistochemical Study of Gastric Mucosa and Critical Review Indicate That the Subepithelial Telocytes Are Prelymphatic Endothelial Cells

Contact Info

Product

Resources

About