subsp. () is a strong pathogen toward lepidopteran larvae thanks to specific Cry toxins causing leaky gut phenotypes. Hence, and its toxins are used worldwide as microbial insecticide and in genetically modified crops, respectively, to fight crop pests. However, belongs to the group, some strains of which are well known human opportunistic pathogens. Therefore, ingestion of along with food may threaten organisms not susceptible to infection. Here we show that Cry1A toxins induce enterocyte death and intestinal stem cell (ISC) proliferation in the midgut of , an organism non-susceptible to . Surprisingly, a high proportion of the ISC daughter cells differentiate into enteroendocrine cells instead of their initial enterocyte destiny. We show that Cry1A toxins weaken the E-Cadherin-dependent adherens junction between the ISC and its immediate daughter progenitor, leading the latter to adopt an enteroendocrine fate. Hence, although not lethal to non-susceptible organisms, Cry toxins can interfere with conserved cell adhesion mechanisms, thereby disrupting intestinal homeostasis and endocrine functions.
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http://dx.doi.org/10.7554/eLife.80179 | DOI Listing |
Elife
November 2024
Aix-Marseille Université, CNRS, IBDM, Marseille, France.
Multiple gut antimicrobial mechanisms are coordinated in space and time to efficiently fight foodborne pathogens. In , production of reactive oxygen species (ROS) and antimicrobial peptides (AMPs) together with intestinal cell renewal play a key role in eliminating gut microbes. A complementary mechanism would be to isolate and treat pathogenic bacteria while allowing colonization by commensals.
View Article and Find Full Text PDFActa Pharm Sin B
September 2024
Department of Pharmacology & the Key Laboratory of Smart Drug Delivery Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201210, China.
The proper differentiation and reorganization of the intestinal epithelial cell population is critical to mucosal regeneration post injury. Label retaining cells (LRCs) expressing SRY-box transcription factor 9 (SOX9) promote epithelial repair by replenishing LGR5 intestinal stem cells (ISCs). While, LRCs are also considered precursor cells for enteroendocrine cells (EECs) which exacerbate mucosal damage in inflammatory bowel disease (IBD).
View Article and Find Full Text PDFSci Rep
May 2024
Divisions of Gastroenterology and Hepatology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Lack of understanding of the pathophysiology of gastrointestinal (GI) complications in type 1 diabetes (T1D), including altered intestinal transcriptomes and protein expression represents a major gap in the management of these patients. Human enteroids have emerged as a physiologically relevant model of the intestinal epithelium but establishing enteroids from individuals with long-standing T1D has proven difficult. We successfully established duodenal enteroids using endoscopic biopsies from pediatric T1D patients and compared them with aged-matched enteroids from healthy subjects (HS) using bulk RNA sequencing (RNA-seq), and functional analyses of ion transport processes.
View Article and Find Full Text PDFNat Commun
March 2024
National Institute of Biological Sciences, No. 7 Science Park Road, Zhongguancun Life Science Park, Beijing, 102206, China.
The manipulation of cell identity by reprograming holds immense potential in regenerative medicine, but is often limited by the inefficient acquisition of fully functional cells. This problem can potentially be resolved by better understanding the reprogramming process using in vivo genetic models, which are currently scarce. Here we report that both enterocytes (ECs) and enteroendocrine cells (EEs) in adult Drosophila midgut show a surprising degree of cell plasticity.
View Article and Find Full Text PDFSci Adv
February 2024
Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki 00790, Finland.
The adult intestine is a regionalized organ, whose size and cellular composition are adjusted in response to nutrient status. This involves dynamic regulation of intestinal stem cell (ISC) proliferation and differentiation. How nutrient signaling controls cell fate decisions to drive regional changes in cell-type composition remains unclear.
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