{"title":"Coupled Mutual Inhibition and Mutual Activation Motifs as Tools for Cell-Fate Control.","authors":"Burhanuddin Sabuwala, Kishore Hari, Abhishek Shanmuga Vengatasalam, Mohit Kumar Jolly","doi":"10.1159/000529558","DOIUrl":"10.1159/000529558","url":null,"abstract":"<p><p>Multistability is central to biological systems. It plays a crucial role in adaptation, evolvability, and differentiation. The presence of positive feedback loops can enable multistability. The simplest of such feedback loops are (a) a mutual inhibition (MI) loop, (b) a mutual activation (MA) loop, and (c) self-activation. While it is established that all three motifs can give rise to bistability, the characteristic differences in the bistability exhibited by each of these motifs is relatively less understood. Here, we use dynamical simulations across a large ensemble of parameter sets and initial conditions to study the bistability characteristics of these motifs. Furthermore, we investigate the utility of these motifs for achieving coordinated expression through cyclic and parallel coupling amongst them. Our analysis revealed that MI-based architectures offer discrete and robust control over gene expression, multistability, and coordinated expression among multiple genes, as compared to MA-based architectures. We then devised a combination of MI and MA architectures to improve coordination and multistability. Such designs help enhance our understanding of the control structures involved in robust cell-fate decisions and provide a way to achieve controlled decision-making in synthetic systems.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"283-296"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9252904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cells Tissues OrgansPub Date : 2024-01-01Epub Date: 2022-12-12DOI: 10.1159/000528601
Maria Chiara Lionetti, Maria Rita Fumagalli, Caterina A M La Porta
{"title":"Nuclear Biophysical Changes during Human Melanoma Plasticity.","authors":"Maria Chiara Lionetti, Maria Rita Fumagalli, Caterina A M La Porta","doi":"10.1159/000528601","DOIUrl":"10.1159/000528601","url":null,"abstract":"<p><p>Tumor plasticity is an emerging property of tumor cells which allows them to change their phenotype in dependence on the environment. The epithelial-mesenchymal transition plays a crucial role in helping cells acquire a more aggressive phenotype when they are in the mesenchymal state. Herein, we investigated the biophysical changes occurring during phenotypic switching in human melanoma cells, considering the blebbiness of the nuclei, their stiffness, and the involvement of polycombs with lamins. We show that the formation of cellular heterogeneity involves many crucial nuclear changes including the interaction between different types of polycombs with lamins and chromosome accessibility. Altogether, our results shed new light on the molecular mechanisms involved in the formation of a heterogeneous cell population during phenotypic switching. In particular, our results show that phenotypic switching in melanoma involves chromatin remodeling changing the transcriptional activity of cells and consequently their phenotype.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"120-132"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10393933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cells Tissues OrgansPub Date : 2024-01-01Epub Date: 2024-01-18DOI: 10.1159/000536210
Fatma M Abdel-Maksoud, Shimaa Ali, Hanan H Abd-Elhafeez, Kamal E H Abdalla
{"title":"Meckel's Diverticulum in Adult Geese (Alopochen egyptiacus): A Comprehensive Study of Structure Using Histological, Electron Microscopy, and Immunohistochemical Methods.","authors":"Fatma M Abdel-Maksoud, Shimaa Ali, Hanan H Abd-Elhafeez, Kamal E H Abdalla","doi":"10.1159/000536210","DOIUrl":"10.1159/000536210","url":null,"abstract":"<p><strong>Introduction: </strong>The intestine plays an important role in mediating between the bird and its nutritional environment. The yolk stalk, also known as Meckel's diverticulum, is a landmark between the jejunum and ileum. This work aimed to investigate the anatomical, histological, and electron microscopical features of cellular components of the Meckel's diverticulum (MD) in adult geese.</p><p><strong>Methods: </strong>The intestine was dissected from the bird's body cavity, and Meckel's diverticulum was exposed and prepared for light and electron microscopical examinations.</p><p><strong>Results: </strong>Our results revealed that the MD mucosa is thrown up into villi and crypts, and the mucosal epithelium is a columnar epithelium with goblet cells as well as intraepithelial lymphocytes. Lymphoid follicles and numerous immune cells were demonstrated within the lamina propria. The mucous glands were also observed within the lamina propria and among the lymphoid follicles. The lining epithelium of MD appeared with different staining affinities: dark cells (electron-dense) and light cells (electron-lucent) contained few mitochondria and more secretory vesicles, while dark cells contained more mitochondria and fewer secretory vesicles. Immunohistochemical analysis of MD revealed positive immunoreactivity for several markers, such as CD117, chromogranin, PLCβ, cytokeratin, MHC II, and S100.</p><p><strong>Conclusion: </strong>Taken together, our findings suggest that MD is considered an immune organ in adult geese.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"390-402"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139490984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cells Tissues OrgansPub Date : 2024-01-01Epub Date: 2024-03-21DOI: 10.1159/000538438
Christina-Marie Baumbach, Nadia Ayurini Anantama, Vuk Savkovic, Christoph K W Mülling, Jan Schinköthe, Jule Kristin Michler
{"title":"3D Approaches to Culturing Bovine Skin: Explant Culture versus Organotypic Skin Model.","authors":"Christina-Marie Baumbach, Nadia Ayurini Anantama, Vuk Savkovic, Christoph K W Mülling, Jan Schinköthe, Jule Kristin Michler","doi":"10.1159/000538438","DOIUrl":"10.1159/000538438","url":null,"abstract":"<p><strong>Introduction: </strong>Digital dermatitis (DD) in cattle appears with high prevalence; nevertheless, the knowledge on its pathogenesis is still limited. In this context, in vitro skin models represent a valuable tool to facilitate the study of DD.</p><p><strong>Methods: </strong>Two in vitro skin models were established using bovine distal limb skin: a skin explant model and an organotypic skin model. For the skin explant model, skin samples were cultured with an air-liquid interface for up to 7 days. Besides routine histopathological examination, readout parameters were Ki-67 and cleaved Caspase-3 stainings. For the organotypic model, primary keratinocytes were layered on top of a dermal equivalent containing mainly mitotically inactive fibroblasts and maintained for up to 21 days. At regular intervals (days 7, 14, and 21), cultured skin samples were taken for (immuno)histological analysis.</p><p><strong>Results: </strong>Both cultures could be maintained for the entire duration of the intended culture period. In the histopathological assessment, explant skin cultures showed ballooning degeneration of keratinocytes and segmental necrosis starting at day 5 of culturing. Initially, basal keratinocytes in the organotypic model differentiated as demonstrated by positive Keratin 14, Desmoglein-1, Loricrin, and Involucrin immunofluorescent stainings. Ki-67 was observed occasionally and suprabasally still after 21 days of culture.</p><p><strong>Conclusion: </strong>Both in vitro models proved dependable and constitute a viable option for replacing experiments on live animals, each with its own benefits. Whereas skin explants include all cell types available in vivo and can therefore reflect realistic cell-cell interactions and signaling pathways, the organotypic model offers a higher standardization and reproducibility. Depending on the focus of future studies, both models can be used for specific experimental purposes of bovine dermatological research in general or specialized questions concerning (infectious) claw diseases as, e.g., DD.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"424-438"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140173785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mild Synovitis Impairs Chondrogenic Joint Environment.","authors":"Sharada Paudel, Tyler Feltham, Lumanti Manandhar, Yi Guo, Lew Schon, Zijun Zhang","doi":"10.1159/000532008","DOIUrl":"10.1159/000532008","url":null,"abstract":"<p><p>The impact of mild synovitis on the chondrogenic environment in the joint pertaining to cartilage repair is often neglected. In this study, 21 synovial samples were collected from foot surgeries for histology and isolation of fibroblast-like synoviocytes (FLSs). Of the 21 samples, 13 were normal and eight were mild synovitis, according to their synovitis scores. In mild synovitis, CD3+ lymphocytes were increased in the sublining layer. When chondrocytes were cultured and treated with the conditioned medium produced by FLSs, their glycosaminoglycan production was negatively correlated with the synovitis scores of the synovium, from which FLSs were isolated. In conclusion, mild synovitis in common joint conditions compromises the process of chondrogenesis, via inhibiting chondrocyte matrix production by FLSs. The results suggest that the concomitant synovitis, even being mild, could significantly alter the joint environment for chondrogenesis and impair the outcome of cartilage repair.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"245-254"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11152049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10286845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cells Tissues OrgansPub Date : 2024-01-01Epub Date: 2023-04-12DOI: 10.1159/000528501
Padmalochini Selvamani, Raghunath Chelakkot, Amitabha Nandi, Mandar M Inamdar
{"title":"Emergence of Spatial Scales and Macroscopic Tissue Dynamics in Active Epithelial Monolayers.","authors":"Padmalochini Selvamani, Raghunath Chelakkot, Amitabha Nandi, Mandar M Inamdar","doi":"10.1159/000528501","DOIUrl":"10.1159/000528501","url":null,"abstract":"<p><p>Migrating cells in tissues are often known to exhibit collective swirling movements. In this paper, we develop an active vertex model with polarity dynamics based on contact inhibition of locomotion (CIL). We show that under this dynamics, the cells form steady-state vortices in velocity, polarity, and cell stress with length scales that depend on polarity alignment rate (ζ), self-motility (v0), and cell-cell bond tension (λ). When the ratio λ/v0 becomes larger, the tissue reaches a near jamming state because of the inability of the cells to exchange their neighbors, and the length scale associated with tissue kinematics increases. A deeper examination of this jammed state provides insights into the mechanism of sustained swirl formation under CIL rule that is governed by the feedback between cell polarities and deformations. To gain additional understanding of how active forcing governed by CIL dynamics leads to large-scale tissue dynamics, we systematically coarse-grain cell stress, polarity, and motility and show that the tissue remains polar even on larger length scales. Overall, we explore the origin of swirling patterns during collective cell migration and obtain a connection between cell-level dynamics and large-scale cellular flow patterns observed in epithelial monolayers.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"269-282"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9295460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cells Tissues OrgansPub Date : 2024-01-01Epub Date: 2023-08-16DOI: 10.1159/000533644
Furkan Erdoğan, Arife Ahsen Kaplan, Hüseyin Sina Coşkun, Gamze Altun, Berrin Zuhal Altunkaynak, Ebru Kelsaka, Suleyman Kaplan, Ahmet Pişkin
{"title":"Momordica charantia Enhances Tendon Healing in Rats: An Experimental Study.","authors":"Furkan Erdoğan, Arife Ahsen Kaplan, Hüseyin Sina Coşkun, Gamze Altun, Berrin Zuhal Altunkaynak, Ebru Kelsaka, Suleyman Kaplan, Ahmet Pişkin","doi":"10.1159/000533644","DOIUrl":"10.1159/000533644","url":null,"abstract":"<p><p>Momordica charantia (MC) is a traditional plant widely used since ancient times for wound healing. This study evaluated its potential effects on tendon healing. Adult male Wistar albino rats (n = 32, 8 rats in each group) were anesthetized, and their Achilles tendons were prepared for surgical procedures. Group 1 (Cont = control group) was not subjected to any surgery and was used as a control group for baseline values. Group 2 (PR = primary repair group) underwent primary repair (PR) with a monofilament suture after a full-thickness incision of the Achilles tendon. A full-thickness incision was also made to the Achilles tendon of group 3 (CT = collagen tube-administered group), followed by PR and collagen tube insertion. In group 4 (MC = M. charantia-administered group), 1 mL of MC extract was applied locally on the collagen tube in addition to the surgical procedure applied to group 3. The Achilles tendons were excised on the postoperative 40th day and examined stereologically, histologically, and bioinformatically. Data showed that the total volume of the collagen fibers was higher in MC and CT groups than in the PR group. The total volume of the tendon was decreased in MC and CT groups than in the Cont group. The ratios between the volumes of the collagen fibers and total tendon in the MC and CT groups were significantly different from PR, but not different from the Cont group. Additionally, MC improved tenoblastic activity, collagen production, and neovascularization. Bioinformatic interactions showed that the proteases of MC could trigger the signals playing a role on vasculogenesis, reducing inflammation, and contributing to tenoblast activation and collagen remodeling. MC extract ameliorates the healing of injured tendon and can provide satisfactory tendon repair. Further works are recommended to explore the healing capacity of MC.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"304-315"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10367404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cells Tissues OrgansPub Date : 2024-01-01Epub Date: 2024-02-15DOI: 10.1159/000537838
Cecibel M León-Félix, Andrea Q Maranhão, Christiani A Amorim, Carolina M Lucci
{"title":"Optimizing Decellularization of Bovine Ovarian Tissue: Toward a Transplantable Artificial Ovary Scaffold with Minimized Residual Toxicity and Preserved Extracellular Matrix Morphology.","authors":"Cecibel M León-Félix, Andrea Q Maranhão, Christiani A Amorim, Carolina M Lucci","doi":"10.1159/000537838","DOIUrl":"10.1159/000537838","url":null,"abstract":"<p><strong>Introduction: </strong>The decellularized extracellular matrix (dECM) from ovarian tissue could be the best scaffold for the development of a transplantable artificial ovary. Typically, dECM from ovarian tissue has been obtained using sodium dodecyl sulfate (SDS), at a concentration of 1% for 24 h. However, SDS can leave residues in the tissue, which may be toxic to the seeded cells. This study aimed to obtain dECM from bovine ovarian tissue using SDS and NaOH at a minimum concentration in the shortest incubation time.</p><p><strong>Methods: </strong>The respective SDS and NaOH concentrations investigated were 1% and 0.2 <sc>m</sc>; 0.5% and 0.1 <sc>m</sc>; 0.1% and 0.02 <sc>m</sc>; and 0.05% and 0.01 <sc>m</sc>, with 24-, 12-, and 6-h incubation periods. After the incubation time, the tissue was washed in 50 mL of distilled water for 6 h.</p><p><strong>Results: </strong>Histological analysis confirmed decellularization and showed the conservation of collagen fibers in all samples following treatment. Furthermore, the lowest SDS and NaOH concentrations that showed no DNA remaining during electrophoresis analysis were 0.1% and 0.02 <sc>m</sc> when incubated for 24 and 12 h. DNA quantification resulted in <0.2 ng DNA/mg ovarian tissue using these protocols. Additionally, the coculture of dECM (obtained by 0.1% SDS and 0.02 <sc>m</sc> NaOH for 12 h) with ovarian cells showed that there was no toxic effect for the cells for up to 72 h.</p><p><strong>Conclusion: </strong>The protocol involving 0.1% SDS and 0.02 <sc>m</sc> NaOH for 12-h incubation decellularizes bovine ovarian tissue, generating a dECM that preserves the native ECM morphology and is nontoxic to ovarian cells.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"413-423"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139740478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cells Tissues OrgansPub Date : 2024-01-01Epub Date: 2024-05-20DOI: 10.1159/000539415
Eleni Miliotou, Irene de Lázaro
{"title":"A Youthful Touch: Reversal of Aging Hallmarks by Cell Reprogramming.","authors":"Eleni Miliotou, Irene de Lázaro","doi":"10.1159/000539415","DOIUrl":"10.1159/000539415","url":null,"abstract":"<p><strong>Background: </strong>With the elderly population projected to double by 2050, there is an urgent need to address the increasing prevalence of age-related debilitating diseases and ultimately minimize discrepancies between the rising lifespan and stagnant health span. Cellular reprogramming by overexpression of Oct3/4, Klf4, Sox2, and cMyc (OKSM) transcription factors is gaining attention in this context thanks to demonstrated rejuvenating effects in human cell cultures and live mice, many of which can be uncoupled from dedifferentiation and loss of cell identity.</p><p><strong>Summary: </strong>Here, we review current evidence of the impact of cell reprogramming on established aging hallmarks and the underlying mechanisms that mediate these effects. We also provide a critical assessment of the challenges in translating these findings and, overall, cell reprogramming technologies into clinically translatable antiaging interventions.</p><p><strong>Key messages: </strong>Cellular reprogramming has the potential to reverse at least partially some key hallmarks of aging. However, further research is necessary to determine the biological significance and duration of such changes and to ensure the safety of cell reprogramming as a rejuvenation approach. With this review, we hope to stimulate new research directions in the quest to extend health span effectively.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"538-550"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141069884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}