Cell Reports, Год журнала: 2020, Номер 32(6), С. 108007 - 108007
Опубликована: Авг. 1, 2020
Язык: Английский
Nature Communications, Год журнала: 2021, Номер 12(1)
Опубликована: Фев. 26, 2021
The precise spatiotemporal control of cell proliferation is key to the morphogenesis epithelial tissues. Epithelial divisions lead tissue crowding and local changes in force distribution, which turn suppress rate divisions. However, molecular mechanisms underlying this mechanical feedback are largely unclear. Here, we identify a critical requirement B-plexin transmembrane receptors response crowding-induced forces during embryonic skin development. Epidermal stem cells lacking B-plexins fail sense compression, resulting disinhibition transcriptional coactivator YAP, hyperproliferation, overgrowth. Mechanistically, show that mediate mechanoresponses through stabilization adhesive junctions lowering cortical stiffness. Finally, provide evidence B-plexin-dependent mechanochemical also pathophysiologically relevant limit tumor growth basal carcinoma, most common type cancer. Our data define central role mechanosensation couple density division development disease.
Язык: Английский
Процитировано
58
Science Advances, Год журнала: 2022, Номер 8(41)
Опубликована: Окт. 14, 2022
Niche-derived factors regulate tissue stem cells, but apart from the mechanosensory pathways, effect of niche geometry is not well understood. We used organoids and bioengineered culture platforms to demonstrate that conical shape Lgr5 + small intestinal cells (ISCs) facilitate their self-renewal function. Inhibition non-muscle myosin II (NM II)–driven apical constriction altered ISC reduced curvature cell capacity. Niche decreased in aged mice, suggesting suboptimal interactions between old ISCs develop with age. show activation NM IIC or physical restriction young topology improves vitro regeneration by epithelium. propose increase lateral surface area induced promotes neighboring curved has evolved maximize signaling cells.
Язык: Английский
Процитировано
42
Frontiers in Cell and Developmental Biology, Год журнала: 2023, Номер 11
Опубликована: Май 19, 2023
Adult stem cells (ASCs) reside throughout the body and support various tissue. Owing to their self-renewal capacity differentiation potential, ASCs have potential be used in regenerative medicine. Their survival, quiescence, activation are influenced by specific signals within microenvironment or niche. In better words, cell function is significantly extrinsic derived from The niche a complex dynamic network surrounding that plays crucial role maintaining stemness. Studies on suggested aged contributes decline function. Notably, functional loss of highly associated with aging age-related disorders. comprised interactions between multiple types. Over years, essential aspects been revealed, including cell-cell contact, extracellular matrix interaction, soluble signaling factors, biochemical biophysical signals. Any alteration causes damage affects properties cells. A pristine might for proper functioning maintenance tissue homeostasis. this regard, niche-targeted interventions may alleviate problems behavior. purpose perspective discuss recent findings field aging, heterogeneity niches, impact changes We further focused how homeostasis, progression malignant diseases. Finally, we detail therapeutic strategies repair, particular emphasis aging.
Язык: Английский
Процитировано
26
Science, Год журнала: 2024, Номер 386(6725)
Опубликована: Ноя. 28, 2024
Stem cells perceive and respond to biochemical physical signals maintain homeostasis. Yet, it remains unclear how stem sense mechanical from their niche in vivo. In this work, we investigated the roles of PIEZO mechanosensitive channels intestinal cell (ISC) niche. We used mouse genetics single-cell RNA sequencing analysis assess requirement for ISC maintenance. vivo measurement basement membrane stiffness showed that ISCs reside a more rigid microenvironment at bottom crypt. Three-dimensional two-dimensional organoid systems combined with bioengineered substrates stretching device revealed extracellular stimuli modulate function. This study delineates mechanistic cascade activation coordinates fate decision
Язык: Английский
Процитировано
11
Free Radical Biology and Medicine, Год журнала: 2025, Номер unknown
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
1
Reproduction, Год журнала: 2019, Номер unknown
Опубликована: Янв. 1, 2019
Sertoli cells regulate male germ cell proliferation and differentiation are a critical component of the spermatogonial stem (SSC) niche, where homeostasis is maintained by interplay several signaling pathways growth factors. These factors secreted located within seminiferous epithelium, interstitial residing between tubules. peritubular myoid produce glial line-derived neurotrophic factor (GDNF), which binds to RET/GFRA1 receptor complex at surface undifferentiated spermatogonia. GDNF known for its ability drive SSC self-renewal their direct progeny. Even though effects well studied, our understanding regulation expression still limited. The purpose this review discuss how in modulated these mechanisms impact homeostasis.
Язык: Английский
Процитировано
60
Scientific Reports, Год журнала: 2019, Номер 9(1)
Опубликована: Фев. 7, 2019
Abstract Signal transduction pathways are important in physiology and pathophysiology. Targeted drugs aim at modifying pathogenic pathway activity, e.g., cancer. Optimal treatment choice requires assays to measure activity individual patient tissue or cell samples. We developed a method enabling quantitative measurement of functional based on Bayesian computational model inference from measurements mRNA levels target genes the pathway-associated transcription factor . Oestrogen receptor, Wnt, PI3K-FOXO have been described previously. Here, we report development for androgen Hedgehog, TGFβ, NFκB assays, biological validation multiple types, analysis data published clinical studies (multiple sclerosis, amyotrophic lateral contact dermatitis, Ewing sarcoma, lymphoma, medulloblastoma, ependymoma, skin prostate cancer). Multiple cancer (PCa) showed increased AR hyperplasia primary PCa but variable castrate resistant (CR) PCa, loss TGFβ Wnt TMPRSS2:ERG fusion protein-positive active PI3K advanced as potential hormonal resistance pathways. Potential value future practice includes disease subtyping prediction targeted therapy response monitoring.
Язык: Английский
Процитировано
56
Development, Год журнала: 2019, Номер 146(12)
Опубликована: Июнь 15, 2019
Complex 3D tissues arise during development following tightly organized events in space and time. In particular, gene regulatory networks local interactions between single cells lead to emergent properties at the tissue organism levels. To understand design principles of organization, we need characterize individual given times, but also consider collective behavior multiple across different spatial temporal scales. recent years, powerful cell methods have been developed address challenging questions how are formed throughout development, maintained homeostasis, repaired after injury disease. These approaches led a massive increase data pertaining both mRNA protein abundances cells. As review here, these new technologies, combination with toto live imaging, now allow us bridge information quantitatively level generate mechanistic understanding development.
Язык: Английский
Процитировано
56
The EMBO Journal, Год журнала: 2021, Номер 40(11)
Опубликована: Апрель 20, 2021
Язык: Английский
Процитировано
50
Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)
Опубликована: Сен. 27, 2022
Abstract Digestive system diseases arise primarily through the interplay of genetic and environmental influences; there is an urgent need in elucidating pathogenic mechanisms these deploy personalized treatments. Traditional long-established model systems rarely reproduce either tissue complexity or human physiology faithfully; shortcomings underscore for better models. Organoids represent a promising research model, helping us gain more profound understanding digestive organs; this can also be used to provide patients with precise individualized treatment build rapid vitro test models drug screening gene/cell therapy, linking basic clinical treatment. Over past few decades, use organoids has led advanced composition each organ facilitated disease modeling, chemotherapy dose prediction, CRISPR-Cas9 intervention, high-throughput screening, identification SARS-CoV-2 targets, infection. However, existing mainly include epithelial system. In order reveal mechanism diseases, it necessary establish completer physiological organoid model. Combining techniques treatments different formulations approach that requires further exploration. This review highlights advancements field technology from perspectives modeling therapy.
Язык: Английский
Процитировано
31