Adult gastric stem cells and their niches.

Adult gastric stem cells replenish the gastric epithelium throughout life. Recent studies have identified diverse populations of stem cells, progenitor cells, and even differentiated cells that can regain stem cell capacity, so highlighting an unexpected plasticity within the gastric epithelium, both in the corpus and antrum. Two niches seem to co-exist in the gastric unit: one in the isthmus region and the other at the base of the gland, although the precise features of the cell populations and the two niches are currently under debate. A variety of gastric organoid models have been established, providing new insights into niche factors required by the gastric stem cell populations. Here we review our current knowledge of gastric stem cell populations, their markers and interactions, important niche factors, and different gastric organoid systems. For further resources related to this article, please visit the WIREs website.Wellcome-Trus

Organoid Studies in COVID-19 Research

The current COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has completely changed human life for more than two years. Upon the emergence of this new lethal virus, multiple approaches were utilized to gain basic knowledge about its biology. Moreover, modern technologies, such as the organoid model system and next-generation sequencing, enabled us to rapidly establish strategies to tackle the disease, including vaccines and therapeutics. The recently developed organoid technology reflects human physiology more closely than other model systems. Coupled with its rapidness, high efficiency, and outstanding reliability, it has provided an opportunity to develop new drugs and understand the impact of the viral pathogen on the host. Recent findings using organoids have successfully revealed the cellular tropism of the virus in different organs and identified potential drug candidates that impact the disease. This review will summarize current achievements made with organoids in the fight against COVID-19. © 2022 by the Korean Society for Stem Cell Research11Nsciescopu

Exploiting Bacterial Genera as Biocontrol Agents: Mechanisms, Interactions and Applications in Sustainable Agriculture

The rising demand for sustainable agriculture necessitates alternative methods to using chemical pesticides for controlling plant pathogens. Biocontrol involves the use of natural antagonists, such as bacteria, as an alternative to synthetic chemical pesticides, which can be harmful to human health and the environment. This review discusses the potential of Bacillus, Streptomyces, Pseudomonas and Serratia as biocontrol agents (BCAs) against various plant pathogens. These bacteria suppress pathogen growth via various mechanisms, such as antibiosis, nutrient and space competition and systemic resistance, and significantly contribute to plant growth. We provide an overview of the secondary metabolites, plant interactions and microbiota interactions of these bacteria. BCAs offer a promising and sustainable solution to plant pathogens and help maintain the one-health principle.11Nsciescopuskc

A cellular hierarchy of Notch and Kras signaling controls cell fate specification in the developing mouse salivary gland

The development of the mouse salivary gland involves a tip-driven process of branching morphogenesis that takes place in concert with differentiation into acinar, myoepithelial, and ductal (basal and luminal) sub -line-ages. By combining clonal lineage tracing with a three-dimensional (3D) reconstruction of the branched epithelial network and single-cell RNA-seq analysis, we show that in tips, a heterogeneous population of re-newing progenitors transition from a Krt14+ multipotent state to unipotent states via two transcriptionally distinct bipotent states, one restricted to the Krt14+ basal and myoepithelial lineage and the other to the Krt8+ acinar and luminal lineage. Using genetic perturbations, we show how the differential expression of Notch signaling correlates with spatial segregation, exits from multipotency, and promotes the Krt8+ lineage, whereas Kras activation promotes proacinar fate. These findings provide a mechanistic basis for how posi-tional cues within growing tips regulate the process of lineage segregation and ductal patterning.11Nsciescopu

Sensitivity towards HDAC inhibition is associated with RTK/MAPK pathway activation in gastric cancer

Gastric cancer ranks the fifth most common and third leading cause of cancer-related deaths worldwide. Alterations in the RTK/MAPK, WNT, cell adhesion, TP53, TGF beta, NOTCH, and NF kappa B signaling pathways could be identified as main oncogenic drivers. A combination of altered pathways can be associated with molecular subtypes of gastric cancer. In order to generate model systems to study the impact of different pathway alterations in a defined genetic background, we generated three murine organoid models: a RAS-activated (Kras(G12D), Tp53(R172H)), a WNT-activated (Apc(fl/fl), Tp53(R172H)), and a diffuse (Cdh1(fl/fl), Apc(fl/fl)) model. These organoid models were morphologically and phenotypically diverse, differed in proteome expression signatures and possessed individual drug sensitivities. A differential vulnerability to RTK/MAPK pathway interference based on the different mitogenic drivers and according to the level of dependence on the pathway could be uncovered. Furthermore, an association between RTK/MAPK pathway activity and susceptibility to HDAC inhibition was observed. This finding was further validated in patient-derived organoids from gastric adenocarcinoma, thus identifying a novel treatment approach for RTK/MAPK pathway altered gastric cancer patients.11Nsciescopu

SCON—a Short Conditional intrON for conditional knockout with one-step zygote injection

The generation of conditional alleles using CRISPR technology is still challenging. Here, we introduce a Short Conditional intrON (SCON, 189 bp) that enables the rapid generation of conditional alleles via one-step zygote injection. In this study, a total of 13 SCON mouse lines were successfully generated by 2 different laboratories. SCON has conditional intronic functions in various vertebrate species, and its target insertion is as simple as CRISPR/Cas9-mediated gene tagging. © 2022, The Author(s).11Nsciescopuskc