Differentiation最新文献

{"title":"Myogenic and adipogenic potential of porcine muscle satellite cells isolated by flow cytometry","authors":"A. Vincent ,&nbsp;K. Stange ,&nbsp;I. Louveau ,&nbsp;M. Röntgen ,&nbsp;F. Dessauge","doi":"10.1016/j.diff.2025.100871","DOIUrl":"10.1016/j.diff.2025.100871","url":null,"abstract":"<div><div>Skeletal muscle mesenchymal stromal cells (MSCs) are resident cells in the stromal, interstitial or perivascular areas, with satellite cells (SCs) acting as essential precursors for muscle growth and regeneration. This study firstly aimed to phenotype freshly isolated SCs using cell surface markers and gene expression and to assess their ability to differentiate in myogenic or adipogenic conditions. Then, refined SCs populations sorted according to the myogenic CD56 cell surface marker were characterized. SCs were isolated from the l<em>ongissimus</em> muscle of 5-7-day-old piglets and analyzed using flow cytometry. The hematopoietic CD45 + cells represented 20 % of the total isolated cell population. The myogenic CD29 and CD56 positive cell populations were the most abundant (80 % and 50 % respectively). Mesenchymal CD90 positive cells were also highly present (34 %) while the proportions of fibro-adipogenic CD140a and CD34-positive cells were low (&lt;3 %). In this study, we showed that total isolated muscle-derived SCs were able to differentiate into myotubes in both myogenic and adipogenic media. Transcriptional profiles were similar, except for PPARγ, PGC1α, and Myosin Heavy Chain 2B witch present a higher induction during differentiation in the adipogenic medium. Interestingly, non-hematopoietic CD45⁻sorted cells further separated in CD45-/CD56+ and also CD45-/CD56-sub-populations mostly formed myotubes under both conditions, with CD56⁻cells showing potential and gene expression profile of myoblasts. Mature adipocytes were found in the CD45-/CD56+ group after differentiation in adipogenic medium. This study increases knowledge on myogenic cell surface marker and underscores the complexity and heterogeneity of muscle SCs.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"144 ","pages":"Article 100871"},"PeriodicalIF":2.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “The mechanism of EGF in promoting skeletal muscle post-injury regeneration” [Differentiation 143 (2025) 100862]","authors":"Huaixin Teng ,&nbsp;Yongze Liu ,&nbsp;Ruotong Hao ,&nbsp;Lu Zhang ,&nbsp;Xiaoyu Zhang ,&nbsp;Shufeng Li ,&nbsp;Shuang Li ,&nbsp;Huili Tong","doi":"10.1016/j.diff.2025.100885","DOIUrl":"10.1016/j.diff.2025.100885","url":null,"abstract":"","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"144 ","pages":"Article 100885"},"PeriodicalIF":2.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144522185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteins and peptides responsible for bone remodeling","authors":"Jorge Alejandro Barbosa-Nuñez ,&nbsp;José Nabor Haro-González ,&nbsp;Eristeo García-Márquez ,&nbsp;Hugo Espinosa-Andrews ,&nbsp;Eduardo Padilla-Camberos ,&nbsp;Sara Elisa Herrera-Rodríguez","doi":"10.1016/j.diff.2025.100872","DOIUrl":"10.1016/j.diff.2025.100872","url":null,"abstract":"<div><div>Bones are living tissues that are periodically renewed through the bone remodeling process. It starts when monocyte-macrophage-type cells begin to proliferate and recruit into the bone tissue due to the action of various proteins. The proteins are generated by the body in response to a lack of calcium in the blood or a damaged bone tissue. Then, other chemical signals promote the differentiation of monocyte-macrophage-type cells into osteoclasts. Finally, osteoclasts carry out a process known as bone resorption in which they degrade bone tissue. After, bone resorption a process known as osteogenesis takes place. In osteogenesis, pluripotent mesenchymal stem cells proliferate and recruit in the bone damaged by bone resorption in response to the action of different compounds. Then, pluripotent mesenchymal stem cells differentiate into osteoblasts due to the effect of specific proteins. Finally, osteoblasts generate new bone tissue, completing the bone remodeling process. This review aims to summarize and provide recent findings of the proteins and chemical signals involved in osteoclast and osteoblast proliferation, recruitment and maturation during the bone resorption and osteogenesis processes. The information found about these molecules could help to better understand all the complex mechanisms that directly or indirectly influence the bone remodeling process. In this sense, the mechanisms of different bone disorders and diseases could be elucidated in a better way, leading to the generation of efficient and specific treatments for each of them in the future.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"144 ","pages":"Article 100872"},"PeriodicalIF":2.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144189633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One Wnt to lead them all: a Wnt1 primer","authors":"Arne C. Lekven,&nbsp;Sarah Empie ,&nbsp;Richard Saoud","doi":"10.1016/j.diff.2025.100884","DOIUrl":"10.1016/j.diff.2025.100884","url":null,"abstract":"<div><div>Wnt1 was originally identified by virtue of its mutant phenotype in Drosophila and its causation of mammary tumors in mice, but, in its history, Wnt1 has been a nexus for ground-breaking discoveries in developmental biology, evolutionary biology, and disease. Wnt1 orthologs are found across the animal kingdom and play a role in a multitude of developmental and homeostatic mechanisms involving proliferation, cell fate specification, stem cell maintenance and tissue homeostasis. In vertebrates, Wnt1 is located in a syntenic chromosome neighborhood that is essential to its conserved expression in the developing nervous system. Wnt1 is essential for nervous system development, in particular for the midbrain and anterior hindbrain. Wnt1 also is essential for bone homeostasis, and mutant alleles are behind severe cases of recessive osteogenesis imperfecta in humans. This primer reviews the illustrious history of Wnt1, its gene structure and regulation, expression, loss-of-function consequences, and connection to human disease.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"144 ","pages":"Article 100884"},"PeriodicalIF":2.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144489522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of seeding cell density for differentiation of adipose-derived stem cells into epithelial-like cells on bioengineered composite scaffolds","authors":"Yourka D. Tchoukalova ,&nbsp;Manisha K. Shah ,&nbsp;Cheryl E. Myers ,&nbsp;Nan Zhang ,&nbsp;David G. Lott","doi":"10.1016/j.diff.2025.100870","DOIUrl":"10.1016/j.diff.2025.100870","url":null,"abstract":"<div><div>This study investigates the biological factors influencing the epithelial differentiation of adipose-derived stem cells (ASC) to develop an engineered upper airway construct. One fraction of ASC was seeded onto a fibrin sealant (Tisseel) matrix encompassing an additional equal fraction of ASC that has been integrated into a porous polyethylene scaffold (Medpor®). Constructs with ASC seeded at total densities of 5 × 10⁵, 1 × 10⁶, 2.5 × 10⁶, and 5 × 10⁶ cells cm-2 were cultured under submerged conditions for 11 days to achieve partial epithelial differentiation (PD). To simulate post-transplantation exposure to air and interaction with host epithelial cells, PD constructs with ASC at 5 × 10⁶ cells cm-2 were transitioned to air-liquid interface (ALI) conditions for additional 10 days (PD/ALI-21d) or 21 days (PD/ALI-32d). The latter cultures were either maintained alone or co-cultured with bronchial epithelial cells (PD/ALI-32d + BEAS). Gene expressions of mesenchymal and epithelial basal, secretory, and ciliated cell markers were assessed and validated via immunohistochemistry.</div><div>ASC seeded at 5 × 10⁶ cells cm-2 achieved the highest partial epithelial differentiation, supporting the use of this density for further experiments. In PD/ALI-21d, basal and secretory epithelial marker gene expression significantly increased, while ciliated cell markers remained unchanged. In PD/ALI-32d, expression of basal and goblet cell markers and several mesenchymal stem cell markers decreased, but co-culturing with BEAS maintained the levels of their expression. These results indicate that long-term ALI cultures cannot sustain terminal differentiation of ASC into secretory phenotypes without co-culture with primary epithelial cells.</div><div>In conclusion, partially differentiated ASC on constructs maintain a stem cell phenotype and may promote differentiation into basal/secretory phenotypes, but not ciliated cells. Enhancing ciliogenesis and ensuring ASC commitment to the epithelial lineage, require modifications to the study design.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"143 ","pages":"Article 100870"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Wu et al","authors":"Matthew J. Anderson,&nbsp;Mark Lewandoski","doi":"10.1016/j.diff.2025.100865","DOIUrl":"10.1016/j.diff.2025.100865","url":null,"abstract":"","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"143 ","pages":"Article 100865"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the reorganization of F-actin for cell-based implantation cartilage repair therapies","authors":"Alissa T. Rzepski ,&nbsp;Mandy M. Schofield ,&nbsp;Stephanie Richardson-Solorzano ,&nbsp;Mark L. Arranguez ,&nbsp;Alvin W. Su ,&nbsp;Justin Parreno","doi":"10.1016/j.diff.2025.100847","DOIUrl":"10.1016/j.diff.2025.100847","url":null,"abstract":"<div><div>Articular cartilage is an avascular tissue that allows for frictionless mobility of joints. Unfortunately, cartilage is incapable of self-repair and any damage leads to degradation in osteoarthritis (OA). Autologous chondrocyte implantation therapies are currently being used to treat focal cartilage defects caused by post-traumatic OA (PTOA). For chondrocyte implantation, chondrocytes are isolated from healthy regions of cartilage from damaged joints, expanded on stiff polystyrene to increase cell number, and reimplanted into damaged areas to stimulate repair. Unfortunately, chondrocyte implantations can ultimately fail as chondrocytes dedifferentiate during expansion. In dedifferentiation, chondrocytes increase in size, elongate, and express contractile cytoskeletal molecules. Furthermore, cells produce a fibroblastic matrix which is biomechanically inferior to articular cartilage matrix. Therefore, developing a greater understanding of dedifferentiation is imperative. In the dedifferentiation process, cellular actin filaments reorganize from a cortical organization into stress fibers. The formation of stress fibers plays a crucial role in chondrocyte dedifferentiation by regulating chondrocyte cell morphology and gene expression. Determining the actin-based molecular underpinnings in chondrocyte dedifferentiation may enable the specific targeting of stress fibers to promote redifferentiation of passaged cells and improve chondrocyte implantation outcomes. This review focuses on how targeting regulators of actin filament organization may promote the redifferentiation of expanded chondrocytes for implantation, thus increasing potential therapeuticlongevity.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"143 ","pages":"Article 100847"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143593912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune Cell-NSPC interactions: Friend or foe in CNS injury and repair?","authors":"Chih-Wei Zeng","doi":"10.1016/j.diff.2025.100855","DOIUrl":"10.1016/j.diff.2025.100855","url":null,"abstract":"<div><div>Neural stem/progenitor cells (NSPCs) play a crucial role in central nervous system (CNS) development, regeneration, and repair. However, their functionality and therapeutic potential are intricately modulated by interactions with immune cells, particularly macrophages and microglia. Microglia, as CNS-resident macrophages, are distinct from peripheral macrophages in their roles and characteristics, contributing to specialized functions within the CNS. Recent evidence suggests that microglia, as CNS-resident macrophages, contribute to the quality assurance of NSPCs by eliminating stressed or dysfunctional cells, yet the mechanisms underlying this process remain largely unexplored. Furthermore, macrophage polarization states, such as M1 and M2, appear to differentially influence NSPC quality, potentially impacting neurogenesis and regenerative outcomes. Identifying surface markers indicative of NSPC stress could provide a strategy for selecting optimal cells for transplantation therapies. Additionally, <em>in vivo</em> clonal labeling approaches may enable precise tracking of NSPC fate and their interactions with immune cells. Beyond macrophages and microglia, the roles of other immune cells, including T cells and neutrophils, particularly in injury and neurodegenerative disease contexts, in the context of CNS injury and disease are emerging areas of interest. Here, I discuss the emerging evidence supporting the interplay between the immune system and NSPCs, highlighting critical gaps in knowledge and proposing future research directions to harness immune-mediated mechanisms for optimizing neural regeneration and transplantation strategies.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"143 ","pages":"Article 100855"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholecystokinin-antagonist lorglumide inhibits osteogenic differentiation in human bone marrow stem cells","authors":"Catharina Marques Sacramento,&nbsp;Márcio Zaffalon Casati,&nbsp;Enilson Antonio Sallum,&nbsp;Renato Corrêa Viana Casarin,&nbsp;Karina Gonzales Silvério","doi":"10.1016/j.diff.2025.100867","DOIUrl":"10.1016/j.diff.2025.100867","url":null,"abstract":"<div><h3>Background</h3><div>The relationship between gastrointestinal hormones and bone metabolism has gained significant attention, but the specific role of cholecystokinin (CCK) in bone homeostasis remains largely unexplored. This study aimed to evaluate the role of the CCK pathway in osteogenic differentiation by blocking its mechanisms in human bone marrow stem cells (hBMSCs).</div></div><div><h3>Methods</h3><div>hBMSCs were exposed to Lorglumide, a CCK signaling pathway inhibitor, under osteogenic conditions. Cell viability, osteogenic differentiation, RT-qPCR analysis of CCK, FOS, OCN, and RUNX2, IP3 receptor phosphorylation, alkaline phosphatase (ALP) activity, and calcium concentration (Ca²) were assessed to elucidate Lorglumide's effects on osteogenesis and related mechanisms.</div></div><div><h3>Results</h3><div>Lorglumide reduced hBMSC viability at concentrations ≥30 μM over 14 days. Mineralization assays revealed dose-dependent inhibition, with 20 μM maintaining mineralization comparable to controls. RT-qPCR showed that Lorglumide suppressed CCK expression and altered osteogenic gene expression (FOS, RUNX2, OCN). Lorglumide decreased Ca² concentration compared to osteogenic medium (OM) and reduced ALP activity, indicating its inhibitory effect on key osteogenic mechanisms.</div></div><div><h3>Conclusion</h3><div>Lorglumide inhibits hBMSC osteoblastic differentiation, suggesting a possible role for the CCK signaling pathway in bone metabolism. These findings emphasize the involvement of gastrointestinal hormones in bone homeostasis, suggesting new therapeutic opportunities targeting hormonal regulation to promote bone health. Further studies are needed to explore the underlying mechanisms and potential clinical applications of modulating CCK pathways in bone-related disorders.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"143 ","pages":"Article 100867"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progression of differentiation of iPSCs into specific subtypes of neurons","authors":"Jingwen Wang ,&nbsp;Ruijie Ji ,&nbsp;Lei Zhang ,&nbsp;Xiang Cheng ,&nbsp;Xinhua Zhang","doi":"10.1016/j.diff.2025.100869","DOIUrl":"10.1016/j.diff.2025.100869","url":null,"abstract":"<div><div>Induced pluripotent stem cells (iPSCs), generated through somatic cell reprogramming, exhibit self-renewal capacity and multilineage differentiation potential. In recent years, iPSC-derived neurons have emerged as a significant platform for researching mechanisms and developing therapies for neurological diseases. This paper reviews the targeted differentiation strategies of iPSCs into dopaminergic neurons, motor neurons, cholinergic neurons and medium spinal neurons, providing detailed insights into the differentiation processes. Additionally, this paper discusses the challenges associated with the future application of iPSCs-derived neurons in the treatment of nervous system diseases are also discussed in this paper, aiming to provide references for the application of iPSCs in cellular therapies for neurodegenerative disorders.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"143 ","pages":"Article 100869"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144167235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}