Homo- and heterodimerization of bHLH transcription factors balance stemness with bipotential differentiation in theDrosophilagut DOI Creative Commons
Aleix Puig-Barbe,

Svenja Dettmann,

Vinícius Dias Nirello

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2019, Volume and Issue: unknown

Published: June 27, 2019

ABSTRACT Multipotent adult stem cells must balance self-renewal with differentiation into various mature cell types. How this is regulated at the transcriptional level poorly understood. Here we show that a network of basic Helix-Loop-Helix (bHLH) transcription factors controls both stemness and bi-potential in Drosophila intestine. We find homodimers Daughterless (Da), homolog mammalian E proteins, maintain intestinal (ISCs), antagonise activity heterodimers Da Scute (Sc), ASCL known regulator secretory differentiation. The HLH factor Extramacrochaetae (Emc), homologous to Id promotes absorptive by titrating Sc to. further Emc prevents committed progenitor (the enteroblast, EB) from de-differentiating, underscoring plasticity these cells. Switching physical interaction partners way enables active maintenance while priming for along two alternative fates. Such regulatory logic could be recapitulated other bipotent systems.

Language: Английский

EGF receptor in organ development, tissue homeostasis and regeneration DOI Creative Commons

Claudia Tito,

Silvia Masciarelli, Gianni Colotti

et al.

Journal of Biomedical Science, Journal Year: 2025, Volume and Issue: 32(1)

Published: Feb. 19, 2025

Abstract The epidermal growth factor receptor (EGFR) is a protein embedded in the outer membrane of epithelial and mesenchymal cells, bone blood immune heart glia stem neural cells. It belongs to ErbB family, which includes three other related proteins: HER2/ErbB2/c-neu, HER3/ErbB3, HER4/ErbB4. EGFR binds seven known signaling molecules, including (EGF) transforming factor-alpha (TGF-α). This binding triggers formation pairs (dimers), self-phosphorylation EGFR, activation several pathways within cell. These influence various cellular processes like proliferation, differentiation, migration, survival. plays critical role both development tissue homeostasis, repair adult organ regeneration. Altered expression linked disruption homeostasis diseases, among cancer. review focuses on how contributes different organs placenta, gut, liver, bone, skin, brain, T cell regulation, pancreas, kidneys, mammary glands lungs along with their associated pathologies. involvement organ-specific branching morphogenesis process also discussed. level activity its impact vary across organs. Factors as affinity ligands, recycling or degradation processes, transactivation by proteins environmental factors (such heat stress smoking) play regulating activity. Understanding EGFR’s regulatory mechanisms holds promise for developing targeted therapeutic strategies.

Language: Английский

Citations

1
Inter-cell type interactions that control JNK signaling in the Drosophila intestine DOI Creative Commons
Peng Zhang,

Stephen M. Pronovost,

Marco Marchetti

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 28, 2024

Abstract JNK signaling is a critical regulator of inflammation and regeneration, but how it controlled in specific tissue contexts remains unclear. Here we show that, the Drosophila intestine, TNF-type ligand, Eiger (Egr), expressed exclusively by intestinal stem cells (ISCs) enteroblasts (EBs), where induced stress during aging. Egr preferentially activates paracrine fashion differentiated enterocytes (ECs) via its receptor, Grindelwald (Grnd). N -glycosylation genes ( Alg3 , Alg9 ) restrain this activation, stress-induced downregulation correlates with suggesting regulatory switch. activity ECs induces expression intermembrane protease Rhomboid (Rho), driving secretion EGFR ligands Keren (Krn) Spitz (Spi), which turn activate progenitor (ISCs EBs) to stimulate their growth division, as well produce more Egr. This study uncovers an -glycosylation-controlled, JNK-EGFR-JNK feedforward loop that sustains ISC proliferation gut regeneration.

Language: Английский

Citations

5
Long-term PM2.5 exposure disrupts corneal epithelial homeostasis by impairing limbal stem/progenitor cells in humans and rat models DOI Creative Commons

Shengjie Hao,

Zhijian Chen, Yuzhou Gu

et al.

Particle and Fibre Toxicology, Journal Year: 2023, Volume and Issue: 20(1)

Published: Sept. 27, 2023

Limbal stem/progenitor cells (LSPCs) play a crucial role in maintaining corneal health by regulating epithelial homeostasis. Although PM2.5 is associated with the occurrence of several diseases, its effects on LSPCs are not clearly understood.

Language: Английский

Citations

11
Pathways regulating intestinal stem cells and potential therapeutic targets for radiation enteropathy DOI Creative Commons

Si-Min Chen,

Bing-Jie Guo,

A Lei Feng

et al.

Molecular Biomedicine, Journal Year: 2024, Volume and Issue: 5(1)

Published: Oct. 10, 2024

Radiotherapy is a pivotal intervention for cancer patients, significantly impacting their treatment outcomes and survival prospects. Nevertheless, in the course of treating those with abdominal, pelvic, or retroperitoneal malignant tumors, procedure inadvertently exposes adjacent intestinal tissues to radiation, posing risks radiation-induced enteropathy upon reaching threshold doses. Stem cells within crypts, through controlled proliferation differentiation, support critical functions epithelium, ensuring efficient nutrient absorption while upholding its protective barrier properties. Intestinal stem (ISCs) regulation intricately orchestrated by diverse signaling pathways, among which are WNT, BMP, NOTCH, EGF, Hippo, Hedgehog NF-κB, each contributing complex control these cells' behavior. Complementing pathways additional regulators such as metabolic states, microbiota, all contribute fine-tuning ISCs behavior crypts. It harmonious interplay cascades modulating elements that preserves homeostasis epithelial (IECs), thereby gut's overall health function. This review delves into molecular underpinnings how respond context radiation enteropathy, aiming illuminate potential biological targets therapeutic intervention. Furthermore, we have compiled summary several current methodologies. By unraveling mechanisms methods, aspire furnish roadmap development novel therapeutics, advancing our capabilities mitigating damage.

Language: Английский

Citations

4
Alterations in ether phospholipids metabolism activate the conserved UPR-Xbp1- PDIA3/ERp60 signaling to maintain intestinal homeostasis DOI Creative Commons

Stephanie Makdissi,

Rihab Loudhaief, Smitha George

et al.

iScience, Journal Year: 2025, Volume and Issue: 28(3), P. 111946 - 111946

Published: Feb. 4, 2025

Language: Английский

Citations

0
Cell growth and the cell cycle: New insights about persistent questions DOI
Jan Inge Øvrebø, Yiqin Ma, Bruce A. Edgar

et al.

BioEssays, Journal Year: 2022, Volume and Issue: 44(11)

Published: Oct. 12, 2022

Abstract Before a cell divides into two daughter cells, it typically doubles not only its DNA, but also mass. Numerous studies in cells ranging from yeast to mammals have shown that cellular growth, stimulated by nutrients and/or growth factor signaling, is prerequisite for cycle progression most types of cells. The textbook view growth‐regulated cycles signaling activates the transcription G1 Cyclin genes induce proliferation, and stimulates anabolic metabolism parallel. However, genetic knockout tests model organisms indicate this whole story, new show additional, “smarter” mechanisms help coordinate with itself. Here we summarize recent advances field, discuss current models which regulates proliferation targeting core regulators via non‐transcriptional mechanisms.

Language: Английский

Citations

17
Genomic alterations in the WNT/β-catenin pathway and resistance of colorectal cancer cells to pathway-targeting therapies DOI Creative Commons
Ioannis A. Voutsadakis

Exploration of Targeted Anti-tumor Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Colorectal cancer is the most prevalent gastrointestinal malignancy with limited therapeutic options in metastatic setting. The WNT/β-catenin/adenomatous polyposis coli (APC) pathway commonly deregulated disease and presents a rational target for exploitation. publicly available genomic data from colorectal cohort of Cancer Genome Atlas (TCGA) were used to define groups cancers alterations APC or other key genes WNT/β-catenin/APC identify characteristics interest each group. In vitro sensitivity drugs targeting compiled Genomics Drug Sensitivity (GDSC) project. Three-fourths possessed about one four these cases also concomitant pathway, including RNF43, CTNNB1, TCF7L2. more three WNT/β-catenin TCF7L2, absence alterations, frequently microsatellite instability (MSI) high had tumor mutation burden (TMB). Cancers same without presented frequency mutations receptor tyrosine kinases, PI3K/AKT genes, DNA damage response genes. Cell lines components displayed numerically greater inhibitors vitro. Groups differing present diverse landscapes that could have implications development pathway.

Language: Английский

Citations

0
Developmental mitochondrial complex I activity determines lifespan DOI
Rhoda Stefanatos, Fiona Robertson, Beatriz Castejón‐Vega

et al.

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

Published: March 17, 2025

Language: Английский

Citations

0
Dapagliflozin ameliorates intestinal stem cell aging by regulating the MAPK signaling pathway in Drosophila DOI Creative Commons
Jinhua Yan,

Chenxi Feng,

H Zhang

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: April 23, 2025

Intestinal stem cells (ISCs) possess the ability to self-renew and differentiate, which is essential for maintaining intestinal tissue homeostasis. However, their functionality significantly declines with age, leading diminished regeneration an increased risk of age-associated diseases. This study investigates effects Dapagliflozin (DAPA), a novel insulin sensitizer SGLT2 inhibitor, on aging ISCs using Drosophila melanogaster model. Our findings demonstrate that DAPA can inhibit MAPK signaling pathway, as confirmed by network pharmacology analysis molecular docking experiments. ameliorates ISC aging, improves function (including enhanced fecal excretion, restored barrier integrity acid-base balance), enhances healthspan. These results highlight potential anti-aging therapeutic agent. provides new evidence application treatment.

Language: Английский

Citations

0
Nutritional and hormonal regulation of mitochondrial biogenesis drives fat body remodeling for reproductive competence DOI Creative Commons
Yiying Li,

Mengyao Lang,

Qiongjie He

et al.

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0