Core clock gene BMAL1 and RNA-binding protein MEX3A collaboratively regulate Lgr5 expression in intestinal crypt cells DOI Creative Commons
Li-Tzu Cheng, Grace Y.T. Tan, Fang–Pei Chang

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Oct. 16, 2023

Abstract The intestinal epithelium is highly regenerative. Rapidly proliferating LGR5 + crypt base columnar (CBC) cells are responsible for epithelial turnover needed to maintain homeostasis. Upon tissue damage, loss of CBCs can be compensated by activation quiescent +4 stem (ISCs) or early progenitor restore regeneration. CBC self-renewal and ISC conversion regulated external signals originating from the niche. In contrast, little known about intrinsic regulatory mechanisms critical maintenance We found that expression in controlled circadian core clock gene BMAL1 BMAL1-regulated RNA-binding protein MEX3A. directly activated transcription Mex3a . MEX3A turn bound stabilized Lgr5 mRNA. Bmal1 depletion reduced led increased ferroptosis, which consequently decreased numbers number expressing marker BMI1. Together, these findings reveal a BMAL1-centered pathway maintains suggest potential mechanism contributing

Language: Английский

Lipid metabolism around the body clocks DOI Creative Commons

Volodymyr Petrenko,

Flore Sinturel, Howard Riezman

et al.

Progress in Lipid Research, Journal Year: 2023, Volume and Issue: 91, P. 101235 - 101235

Published: May 15, 2023

Lipids play important roles in energy metabolism along with diverse aspects of biological membrane structure, signaling and other functions. Perturbations lipid are responsible for the development various pathologies comprising metabolic syndrome, obesity, type 2 diabetes. Accumulating evidence suggests that circadian oscillators, operative most cells our body, coordinate temporal homeostasis. In this review we summarize current knowledge on regulation digestion, absorption, transportation, biosynthesis, catabolism, storage. Specifically, focus molecular interactions between functional clockwork biosynthetic pathways major classes cholesterol, fatty acids, triacylglycerols, glycerophospholipids, glycosphingolipids, sphingomyelins. A growing body epidemiological studies associate a socially imposed misalignment common modern society incidence disorders, however disruption rhythms connection has only been recently revealed. Here, highlight recent unravel mechanistic link intracellular clocks, homeostasis diseases based animal models clock innovative translational humans. We also discuss perspectives manipulating oscillators as potentially powerful approach preventing managing disorders human patients.

Language: Английский

Citations

55
Histone Deacetylase Inhibition by Gut Microbe-Generated Short-Chain Fatty Acids Entrains Intestinal Epithelial Circadian Rhythms DOI Creative Commons

Jibraan A. Fawad,

Deborah Luzader, Gabriel F. Hanson

et al.

Gastroenterology, Journal Year: 2022, Volume and Issue: 163(5), P. 1377 - 1390.e11

Published: Aug. 4, 2022

Language: Английский

Citations

60
Modelling metabolic diseases and drug response using stem cells and organoids DOI Open Access
Wenxiang Hu, Mitchell A. Lazar

Nature Reviews Endocrinology, Journal Year: 2022, Volume and Issue: 18(12), P. 744 - 759

Published: Sept. 7, 2022

Language: Английский

Citations

60
Organoids‐On‐a‐Chip for Personalized Precision Medicine DOI Open Access

Yunqi Man,

Yanfei Liu, Qi‐Wen Chen

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 13, 2024

Abstract The development of personalized precision medicine has become a pivotal focus in modern healthcare. Organoids‐on‐a‐Chip (OoCs), groundbreaking fusion organoid culture and microfluidic chip technology, emerged as promising approach to advancing patient‐specific treatment strategies. In this review, the diverse applications OoCs are explored, particularly their role medicine, potential cutting‐edge technology is highlighted. By utilizing patient‐derived organoids, offer pathway optimize treatments, create precise disease models, investigate mechanisms, conduct drug screenings, individualize therapeutic emphasis on significance technological revolutionizing healthcare improving patient outcomes. Furthermore, transformative future prospects, ongoing advancements field, with genomic multi‐omics integration, ethical frameworks discussed. convergence these innovations can empower patients, redefine approaches, shape

Language: Английский

Citations

7
Ontogeny and function of the circadian clock in intestinal organoids DOI Creative Commons

Andrew E. Rosselot,

Miri Park, Mari Kim

et al.

The EMBO Journal, Journal Year: 2021, Volume and Issue: 41(2)

Published: Oct. 27, 2021

Circadian rhythms regulate diverse aspects of gastrointestinal physiology ranging from the composition microbiota to motility. However, development intestinal circadian clock and detailed mechanisms regulating intestine remain largely unknown. In this report, we show that both pluripotent stem cell-derived human organoids engrafted into mice patient-derived enteroids possess demonstrate phase-dependent necrotic cell death responses Clostridium difficile toxin B (TcdB). Intriguingly, mouse anti-phasic TcdB. RNA-Seq analysis shows ~3-10% detectable transcripts are rhythmically expressed in enteroids. Remarkably, observe gene expression Rac1, a small GTPase directly inactivated by TcdB, between enteroids, disruption Rac1 abolishes clock-dependent responses. Our findings uncover robust functions clock-controlled genes governing organism-specific, responses, lay foundation for organ- disease-specific investigation using translational applications.

Language: Английский

Citations

39
Chronotoxici‐Plate Containing Droplet‐Engineered Rhythmic Liver Organoids for Drug Toxicity Evaluation DOI Creative Commons
Jiaqi Zhou,

Yi‐chun Huang,

Wanlong Wang

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(28)

Published: May 8, 2024

Abstract The circadian clock coordinates the daily rhythmicity of biological processes, and its dysregulation is associated with various human diseases. Despite direct targeting rhythmic genes by many prevalent World Health Organization (WHO) essential drugs, traditional approaches can't satisfy need explore multi‐timepoint drug administration strategies across a wide range drugs. Here, droplet‐engineered primary liver organoids (DPLOs) are generated characteristics in 4 days, developed Chronotoxici‐plate as an vitro high‐throughput automated tool for chronotherapy assessment within 7 days. Cryptochrome 1 ( Cry1 ) identified marker DPLOs, providing insights rapid organoid rhythmicity. Using oxaliplatin representative drug, time‐dependent variations demonstrated toxicity on Chronotoxici‐plate, highlighting importance considering effects. Additionally, role chronobiology underscored modeling. This study may provide tools both precision chronotoxicity development optimizing timing.

Language: Английский

Citations

4
Visual trends and hot research on the relationship between circadian rhythm and gut microbiota: a bibliometric analysis DOI Creative Commons

Weiwei Tang,

Qiao Wen Tan, Jing Cui

et al.

Biological Rhythm Research, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 19

Published: March 17, 2025

Language: Английский

Citations

0
Genetic disruption of the circadian gene Bmal1 in the intestinal epithelium reduces colonic inflammation DOI Creative Commons

Shan Hua,

Ze Zhang, Zhe Zhang

et al.

EMBO Reports, Journal Year: 2025, Volume and Issue: unknown

Published: April 30, 2025

Disruption of the circadian clock is associated with development inflammatory bowel disease (IBD), but underlying mechanisms remain unclear. Here, we observe that mice in early active phase (Zeitgeber time 12, ZT12) are more tolerant to dextran sodium sulfate (DSS)-induced colitis, compared those resting (ZT0). The expression gene Bmal1 peaks and declines phase. knockout intestinal epithelium reduces DSS-induced symptoms. Mechanistically, BMAL1 promotes apoptosis by binding apoptosis-related genes, including Bax, p53, Bak1, their expression. Intriguingly, apoptotic rhythms homeostatic epithelium, while deletion cell apoptosis. Consistently, reducing REV-ERBα agonist SR9009 has best therapeutic efficacy against colitis at ZT0. Collectively, our data demonstrate Bmal1-centered involved injury repair.

Language: Английский

Citations

0
Metabolic Studies in Organoids: Current Applications, Opportunities and Challenges DOI Creative Commons
Elena Richiardone, Valentin Van den Bossche, Cyril Corbet

et al.

Organoids, Journal Year: 2022, Volume and Issue: 1(1), P. 85 - 105

Published: June 13, 2022

Organoid technologies represent a major breakthrough in biomedical research since they offer increasingly sophisticated models for studying biological mechanisms supporting human development and disease. Organoids are three-dimensional (3D) physiological vitro systems that recapitulate the genetic, histological functional features of vivo tissues origin more accurately than classical cell culture methods. In last decade, organoids have been derived from various healthy diseased used wide range applications basic translational research, including (cancer) tissue biology, development, regeneration, disease modeling, precision medicine, gene editing, biobanking drug screening. Here, we report current organoid to study (stem) metabolism several pathophysiological contexts such as cancer metabolic diseases. More precisely, discuss relevance limitations these 3D cultures model (dys)functions associated with hepatic, renal or pancreatic disorders, well tumor progression. We also describe use understand dynamic interaction between diet, microbiota intestinal epithelium. Finally, this review explores recent methodological improvements may help better integrate influence microenvironmental conditions phenotypes.

Language: Английский

Citations

15
Modeling hypothalamic pathophysiology in vitro for metabolic, circadian, and sleep disorders DOI
Helena Leal, Catarina Carvalhas-Almeida, Ana Rita Álvaro

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 35(6), P. 505 - 517

Published: Feb. 1, 2024

Language: Английский

Citations

3