scholarly journals Spatial gene expression maps of the intestinal lymphoid follicle and associated epithelium identify zonated expression programs

PLoS Biology ◽  
2021 ◽  
Vol 19 (10) ◽  
pp. e3001214
Author(s):  
Noam Cohen ◽  
Hassan Massalha ◽  
Shani Ben-Moshe ◽  
Adi Egozi ◽  
Milena Rozenberg ◽  
...  

The intestine is lined with isolated lymphoid follicles (ILFs) that facilitate sampling of luminal antigens to elicit immune responses. Technical challenges related to the scarcity and small sizes of ILFs and their follicle-associated epithelium (FAE) impeded the characterization of their spatial gene expression programs. Here, we combined RNA sequencing of laser capture microdissected tissues with single-molecule transcript imaging to obtain a spatial gene expression map of the ILF and its associated FAE in the mouse small intestine. We identified zonated expression programs in both follicles and FAEs, with a decrease in enterocyte antimicrobial and absorption programs and a partial induction of expression programs normally observed at the villus tip. We further identified Lepr+ subepithelial telocytes at the FAE top, which are distinct from villus tip Lgr5+ telocytes. Our analysis exposes the epithelial and mesenchymal cell states associated with ILFs.

2021 ◽  
Author(s):  
Noam Cohen ◽  
Hassan Massalha ◽  
Shani Ben-Moshe ◽  
Adi Egozi ◽  
Milena Rozenberg ◽  
...  

AbstractThe intestine is lined with isolated lymphoid follicles (ILFs) that facilitate sampling of luminal antigens to elicit immune responses. Technical challenges related to the scarcity and small sizes of ILFs and their follicle-associated epithelium (FAE) impeded the characterization of their spatial gene expression programs. Here, we combined RNA sequencing of laser capture microdissected tissues with single molecule transcript imaging to obtain a spatial gene expression map of the ILF and its associated FAE in the mouse small intestine. We identified zonated expression programs in both follicles and FAEs, with a decrease in enterocyte anti-microbial and absorption programs and a partial induction of expression programs normally observed at the villus tip. We further identified Lepr+ sub-epithelial telocytes at the FAE top, which are distinct from villus-tip Lgr5+ telocytes. Our analysis exposes the epithelial and mesenchymal cell states associated with ILFs.


2012 ◽  
Vol 25 (5) ◽  
pp. 709-721 ◽  
Author(s):  
Anjali A Satoskar ◽  
John P Shapiro ◽  
Cherri N Bott ◽  
Huijuan Song ◽  
Gyongyi M Nadasdy ◽  
...  

2011 ◽  
Vol 17 (2) ◽  
pp. 375-385 ◽  
Author(s):  
Diana Narita ◽  
Edward Seclaman ◽  
Razvan Ilina ◽  
Natalia Cireap ◽  
Sorin Ursoniu ◽  
...  

2020 ◽  
Vol 8 (Suppl 2) ◽  
pp. A23.1-A23
Author(s):  
M Thelen ◽  
MA García-Márquez ◽  
T Nestler ◽  
S Wagener-Ryczek ◽  
J Lehmann ◽  
...  

BackgroundSecondary lymphoid organs (SLO) are involved in induction and enhancement of anti-tumor immune responses on different tumor entities. Recent evidence suggests that anti-tumor immune responses may also be induced or enhanced in the tumor microenvironment in so called tertiary lymphoid structures (TLS). It is assumed that TLS represent a hotspot for T cell priming, B cell activation, and differentiation, leading to cellular and humoral anti-tumor immune response.MethodsFFPE-slides of 120 primary pancreatic ductal adenocarcinoma (PDAC) patients were immunohistochemically (IHC) stained for CD20, CD3, CD8 and HLA-ABC to analyze spatial distribution of tumor-infiltrating lymphocytes. 5-color immunofluorescence staining was performed to further investigate structural components of TLS in comparison to lymphoid follicles in SLOs. Microscope-based laser microdissection and Nanostring-base RNA expression analysis were used to compare gene expression in PDAC, TLS, SLOs and normal pancreatic tissue.ResultsTLS were frequently detected in PDAC and were mainly localized along the invasive tumor margin. In less than 10% of the cases TLS were infiltrating the tumors. Interestingly, 20% of the patients had no TLS. Results of TLS will be correlated with clinical parameters, Immunoscore and immune escape mechanisms. 5-color Immunofluorescence staining revealed similar organization and function of TLS and SLO. Finally, gene expression analyzed by Nanostring revealed largely overlapping expression patterns in TLS and SLO.ConclusionsThe results clearly demonstrate close similarities between SLO and TLS in terms of composition, distribution and gene expression Patterns.Disclosure InformationM. Thelen: None. M.A. García-Márquez: None. T. Nestler: None. S. Wagener-Ryczek: None. J. Lehmann: None. E. Staib: None. F. Popp: None. F. Gebauer: None. P. Lohneis: None. M. Odenthal: None. S. Merkelbach-Bruse: None. C. Bruns: None. K. Wennhold: None. M. von Bergwelt-Baildon: None. H.A. Schlößer: None.


2008 ◽  
Vol 381 (1) ◽  
pp. 59-66 ◽  
Author(s):  
Correne A. DeCarlo ◽  
Nicholas G. Escott ◽  
Julieta Werner ◽  
Kerry Robinson ◽  
Paul F. Lambert ◽  
...  

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