Cell mediated ECM-degradation as an emerging tool for anti-fibrotic strategy

Investigation into the role of cells with respect to extracellular matrix(ECM)remodeling is still in its infancy.Particularly,ECM degradation is an indispensable process during the recovery from fibrosis.Cells with ECM degradation ability due to the secretion of various matrix metalloproteinases(MMPs)have emerged as novel contributors to the treatment of fibrotic diseases.In this review,we focus on the ECM degradation ability of cells associated with the repertoire of MMPs that facilitate the attenuation of fibrosis through the inhibition of ECM deposition.Besides,innovative approaches to engineering and characterizing cells with degradation ability,as well as elucidating the mechanism of the ECM degradation,are also illustrated.Studies conducted to date on the use of cell-based degradation for therapeutic purposes to combat fibrosis are summarized.Finally,we discuss the therapeutic potential of cells with high degradation ability,hoping to bridge the gap between benchside research and bedside applications in treating fibrotic diseases.

Development of a 32-gene signature using machine learning for accurate prediction of inflammatory bowel disease

Inflammatory bowel disease(IBD)is a chronic inflammatory condition caused by multiple genetic and environmental factors.Numerous genes are implicated in the etiology of IBD,but the diagnosis of IBD is challenging.Here,XGBoost,a machine learning prediction model,has been used to distinguish IBD from healthy cases following elaborative feature selection.Using combined unsupervised clustering analysis and the XGBoost feature selection method,we successfully identified a 32-gene signature that can predict IBD occurrence in new cohorts with 0.8651 accuracy.The signature shows enrichment in neutrophil extracellular trap formation and cytokine signaling in the immune system.The probability threshold of the XGBoost-based classification model can be adjusted to fit personalized lifestyle and health status.Therefore,this study reveals potential IBD-related biomarkers that facilitate an effective personalized diagnosis of IBD.

Standard:Human intestinal organoids

Organoids have attracted great interest for disease modelling,drug discovery and development,and tissue growth and homeostasis investigations.However,lack of standards for quality control has become a prominent obstacle to limit their translation into clinic and other applications.“Human intestinal organoids”is the first guideline on human intestinal organoids in China,jointly drafted and agreed by the experts from the Chinese Society for Cell Biology and its branch society:the Chinese Society for Stem Cell Research.This standard specifies terms and definitions,technical requirements,test methods,inspection rules for human intestinal organoids,which is applicable to quality control during the process of manufacturing and testing of human intestinal organoids.It was originally released by the Chinese Society for Cell Biology on 24 September 2022.We hope that the publication of this standard will guide institutional establishment,acceptance and execution of proper practical protocols and accelerate the international standardization of human intestinal organoids for applications.

Standard:Human intestinal cancer organoids

Intestinal cancer is one of the most frequent and lethal types of cancer.Modeling intestinal cancer using organoids has emerged in the last decade.Human intestinal cancer organoids are physiologically relevant in vitro models,which provides an unprecedented opportunity for fundamental and applied research in colorectal cancer.“Human intestinal cancer organoids”is the first set of guidelines on human intestinal organoids in China,jointly drafted and agreed by the experts from the Chinese Society for Cell Biology and its branch society:the Chinese Society for Stem Cell Research.This standard specifies terms and definitions,technical requirements,test methods for human intestinal cancer organoids,which apply to the production and quality control during the process of manufacturing and testing of human intestinal cancer organoids.It was released by the Chinese Society for Cell Biology on 24 September 2022.We hope that the publication of this standard will guide institutional establishment,acceptance and execution of proper practocal protocols,and accelerate the international standardization of human intestinal cancer organoids for clinical development and therapeutic applications.

BMP signaling in cancer stemness and differentiation

The BMP(Bone morphogenetic protein)signaling pathway plays a central role in metazoan biology,intricately shaping embryonic development,maintaining tissue homeostasis,and influencing disease progression.In the context of cancer,BMP signaling exhibits context-dependent dynamics,spanning from tumor suppression to promotion.Cancer stem cells(CSCs),a modest subset of neoplastic cells with stem-like attributes,exert substantial influence by steering tumor growth,orchestrating therapy resistance,and contributing to relapse.A comprehensive grasp of the intricate interplay between CSCs and their microenvironment is pivotal for effective therapeutic strategies.Among the web of signaling pathways orchestrating cellular dynamics within CSCs,BMP signaling emerges as a vital conductor,overseeing CSC self-renewal,differentiation dynamics,and the intricate symphony within the tumor microenvironment.Moreover,BMP signaling’s influence in cancer extends beyond CSCs,intricately regulating cellular migration,invasion,and metastasis.This multifaceted role underscores the imperative of comprehending BMP signaling’s contributions to cancer,serving as the foundation for crafting precise therapies to navigate multifaceted challenges posed not only by CSCs but also by various dimensions of cancer progression.This article succinctly encapsulates the diverse roles of the BMP signaling pathway across different cancers,spanning glioblastoma multiforme(GBM),diffuse intrinsic pontine glioma(DIPG),colorectal cancer,acute myeloid leukemia(AML),lung cancer,prostate cancer,and osteosarcoma.It underscores the necessity of unraveling underlying mechanisms and molecular interactions.By delving into the intricate tapestry of BMP signaling’s engagement in cancers,researchers pave the way for meticulously tailored therapies,adroitly leveraging its dualistic aspects-whether as a suppressor or promoter-to effectively counter the relentless march of tumor progression.

Cross-species single-cell transcriptomic analysis of animal gastric antrum reveals intense porcine mucosal immunity

As an important part of the stomach,gastric antrum secretes gastrin which can regulate acid secretion and gastric emptying.Although most cell types in the gastric antrum are identified,the comparison of cell composition and gene expression in the gastric antrum among different species are not explored.In this study,we collected antrum epithelial tissues from human,pig,rat and mouse for scRNA-seq and compared cell types and gene expression among species.In pig antral epithelium,we identified a novel cell cluster,which is marked by high expression of AQP5,F3,CLCA1 and RRAD.We also discovered that the porcine antral epithelium has stronger immune function than the other species.Further analysis revealed that this may be due to the insufficient function of porcine immune cells.Together,our results replenish the information of multiple species of gastric antral epithelium at the single cell level and provide resources for understanding the homeostasis maintenance and regeneration of gastric antrum epithelium.

The cyclooxygenase-expressing mesenchyme resists intestinal epithelial injury by paracrine signaling

Paracrine signals play pivotal roles in organ homeostasis.Mesenchymal stromal cells(MSCs)play a key role in regulating epithelium homeostasis in the intestine while their paracrine effects are poorly characterized.Here,we identified prostaglandin E2(PGE2)secreted by cyclooxygenase(COX)-expressing MSCs as a vital factor to maintain the intestinal mucosal barrier.We found that MSCs-induced organoid swelling through paracrine effect in vitro,a process due to enhanced water adsorption and is mediated by the COX-PGE2-EP4 axis.To further explore the regulatory effect of this axis on the intestinal epithelial barrier in vivo,we established the conditional knockout mouse model to specifically delete COX in MSCs and found that PGE2 reduction downregulated the gene Muc2 and induced a gastric metaplasia-like phenotype.Moreover,PGE2 defects increased the susceptibility of intestinal epithelium to colitis.Our study uncovers the paracrine signaling of COX-expressing MSCs in intestinal mucosal barrier maintenance,providing a basis for understanding the role of mesenchymal cells in the pathophysiological function of the intestine.