Differentiation最新文献

{"title":"Critical Appraisal of “Osteocyte-like differentiation of osteosarcoma by inorganic phosphate”","authors":"Parth Aphale, Himanshu Shekhar, Shashank Dokania","doi":"10.1016/j.diff.2025.100915","DOIUrl":"10.1016/j.diff.2025.100915","url":null,"abstract":"","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"146 ","pages":"Article 100915"},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145507856","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":"Clinical applications of dental pulp stem cells-derived exosomes in oral and maxillofacial tissue regeneration and repair","authors":"Mahtab Mottaghi ,&nbsp;Camellia Kianbakht ,&nbsp;Shahrzad Samadian ,&nbsp;Alieh Farshbaf ,&nbsp;Majid Mirhashemi ,&nbsp;Farzaneh Ahrari","doi":"10.1016/j.diff.2025.100918","DOIUrl":"10.1016/j.diff.2025.100918","url":null,"abstract":"<div><div>Dental pulp stem cells (DPSCs), as a subclass of mesenchymal stem cells (MSCs), exhibit robust self-renewal capacity and the ability to differentiate into multiple cell lineages. In addition, DPSCs contribute to tissue repair and regeneration through paracrine mechanisms. They secrete cytokines, growth factors, and exosomes that enhance angiogenesis, modulate immune responses and inflammation, promote cell proliferation and migration, limit apoptosis and senescence, and support neuroprotection. Notably, DPSC-derived exosomes carry a unique profile of biomolecules, including microRNAs, which show a potentially safer approach to regeneration and tissue repair. Exosomes derived from DPSCs (DPSC-Exos) can influence the dental microenvironment and promote tissue regeneration in oral and maxillofacial regions, while eliminating the risks linked to direct stem cell transplantation, including immune rejection and unpredictable differentiation. Although there are challenges encountered, including heterogeneity in exosome isolation, culture conditions, the lack of an efficient delivery system, donor variability, and incomplete understanding of their molecular pathways, DPSC-Exos represent a novel frontier in regenerative dentistry and clinical applications in comparison to conventional treatments, such as direct stem cell transplantation. Gaining detailed insight into the miRNA expression patterns within DPSC-Exos is crucial for guiding the design of advanced regenerative therapies. Future investigations should aim to refine experimental procedures and standardize methodologies to achieve reliable outcomes in the therapeutic use of DPSC-Exos. This review highlights the key biological properties of DPSCs that govern the production and function of their exosomes, which underscore their potential applications in successful therapeutic approaches. It also addresses challenges and potential solutions to overcome them.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"146 ","pages":"Article 100918"},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623335","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":"fam20b-dependent proteoglycans do not affect dermal bone formation and fin regeneration, but Bmp signalling promotes fin regenerate outgrowth","authors":"Elham Koosha ,&nbsp;Qian Ma ,&nbsp;Laura Romo Dorantes,&nbsp;Rayan Shafi,&nbsp;B. Frank Eames","doi":"10.1016/j.diff.2025.100914","DOIUrl":"10.1016/j.diff.2025.100914","url":null,"abstract":"<div><div>The role of proteoglycans (PGs) in regulating growth factor signalling during endochondral ossification, or formation of bone around a cartilage template, is established. However, whether PGs regulate other skeletal processes, like intramembranous ossification or fin regeneration, has not been studied extensively. Given that endochondral ossification in PG-deficient <em>fam20b</em> mutant zebrafish is altered due to increased Bmp signalling, we hypothesized that PGs also normally inhibit Bmp signalling during intramembranous ossification and fin regeneration. To test this hypothesis, the functional relevance of Bmp signalling during craniofacial dermal bone formation and caudal fin regeneration was examined in wild type and <em>fam20b</em> mutant zebrafish. Bmp responsiveness of cells around wild-type dermal bones was verified by phospho-Smad1/5/9 immunoreactivity. Dermal bones in <em>fam20b</em> mutants were generally unaffected, apart from early formation of the dentary and quadrate, which actually initiate in the perichondrium of Meckel's cartilage and the palatoquadrate, respectively. Treatment of wild-type or <em>fam20b</em>^{<em>−/−</em>} embryos with the Bmp inhibitor DMH1 did not yield clear differences in the size or morphology of most dermal bones, but did rescue early dentary and quadrate formation in <em>fam20b</em> mutants. During adult fin regeneration, Bmp signalling was confirmed by careful temporal analyses of GFP expression of <em>Tg(5xBmpRE-Xla.Id3:GFP)ir1189</em> and <em>Tg(BmpRE:EGFP)pt510</em> zebrafish, each expressed in different tissue compartments of the regenerating fin. <em>fam20b</em>^{<em>−/−</em>} adults did not show fin regeneration defects. Treatment with DMH1, however, significantly reduced outgrowth of regenerating fins in distinct anatomical regions (the most dorsal and ventral principal rays) in adult zebrafish. Bony ray differentiation also was inhibited by DMH1 treatment. In total, these data do not support a major role of Bmp signalling or <em>fam20b</em>-dependent PGs in craniofacial intramembranous ossification, but do show that Bmp signalling is required for outgrowth of regenerating fins.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"146 ","pages":"Article 100914"},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465385","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":"Regenerative medicine and tissue engineering potential of mesenchymal stem cells exosomes-derived microRNAs","authors":"Navidreza Shayan ,&nbsp;Negin Ghiyasimoghaddam ,&nbsp;Nima Ameli ,&nbsp;Mohammadhasan Baghbani ,&nbsp;Hanieh Alsadat Mirkatuli ,&nbsp;Amir Attaran Khorasani ,&nbsp;Nooshin Mohtasham","doi":"10.1016/j.diff.2025.100911","DOIUrl":"10.1016/j.diff.2025.100911","url":null,"abstract":"<div><div>Mesenchymal stem cells (MSCs) have been revealed as an appropriate candidate for cell-based therapies by isolation from a different range of sources such as bone marrow, umbilical cord, adipose, liver, and orofacial tissues. MSCs showed low immunogenicity, which is considered as a potential alternative therapy for autoimmune and inflammatory diseases. Transplantation of MSCs in different research studies showed that it improves the repairment and regeneration of injured and impaired tissues. MSCs release biologically active molecules, such as extracellular vehicles (EVs) and exosomes (EXOs). EXOs participate in different physiological processes, including immune response, wound healing, bone repair, stem cell maintenance, interaction between the central nervous system (CNS), and pathological impacts in tumorigenesis, inflammation, and heart diseases. Across the tissues, MSCs release exosomes and regenerative molecules and transfer proteins, mRNAs and microRNAs. MicroRNAs (miRNAs) are small noncoding RNAs (21–23 nt) in length that bind to the 3′ untranslated region (3′UTR) of target mRNA and post-transcriptionally regulate gene expression that affects different cellular pathways. More studies are needed relating to the exosome's biogenesis, cellular uptake, trafficking, isolation, qualification, purity, optimization, standardization, and molecular mechanisms of exosome connection with target cells. Recent studies reported promising applications of exosomes derived from various sources in regenerative medicine and tissue engineering approaches. Herein, we are more focused on studies with different approaches in regenerative medicine for tissue repair and healing related to bone, cartilage, tendon-bone, heart, nerves, wounds, skin, and tooth regeneration.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"146 ","pages":"Article 100911"},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145049187","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":"Osteocyte-like differentiation of osteosarcoma by inorganic phosphate","authors":"Yuya Suzuki ,&nbsp;Makoto Takeuchi ,&nbsp;Sumie Koike ,&nbsp;Satoshi Takagi ,&nbsp;Ryohei Katayama","doi":"10.1016/j.diff.2025.100912","DOIUrl":"10.1016/j.diff.2025.100912","url":null,"abstract":"<div><div>Osteosarcoma (OS) cells that deviate from the normal osteogenic differentiation pathway from mesenchymal stem cells (MSCs) to less migratory osteocytes are in an undifferentiated and highly malignant state. β-glycerophosphate (β-gp) is commonly used to induce the osteogenic differentiation of MSCs, inorganic phosphate (Pi) is also widely used to promote MSC differentiation into osteocytes. Recently, OS cells were found to differentiate into an osteocyte-like state by culturing in osteocyte differentiation medium containing β-gp, dexamethasone, and ascorbate. However, whether Pi can induce the osteogenic differentiation of OS cells and its underlying mechanisms remain unclear. In this study, we evaluated the ability of two types of Pi (i.e., disodium phosphate [Na₂HPO₄] and monosodium phosphate [NaH₂PO₄]) to promote the osteogenic differentiation of OS cells. Culturing OS cells in Pi-supplemented medium resulted in increased osteogenic marker gene expression and calcium deposition and reduced cell motility. Notably, Na₂HPO₄ exhibited particularly strong differentiation-inducing effects. Furthermore, our data suggest that WNT5b, a key factor of the noncanonical Wnt signaling pathway, is involved in the Na₂HPO₄-induced osteogenic differentiation of OS cells. These findings suggest that above 3 mM of Na₂HPO₄ function as an inducer of osteocyte-like differentiation in OS cells and that targeting this pathway may offer new therapeutic strategies to suppress OS metastasis.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"146 ","pages":"Article 100912"},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057165","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":"Emerging role of alternative splicing in oral and maxillofacial development","authors":"Yinyu Fu,&nbsp;Bo Yang,&nbsp;Ling Lai,&nbsp;Jun He,&nbsp;Xinzhu Li ,&nbsp;Jin Hou","doi":"10.1016/j.diff.2025.100900","DOIUrl":"10.1016/j.diff.2025.100900","url":null,"abstract":"<div><div>The excision of introns and subsequent ligation of exons in precursor messenger RNA (pre-mRNA) is a fundamental mechanism requisite for the expression of eukaryotic genes. Alternative splicing (AS) serves as a potent amplifying factor, augmenting the spectrum of protein isoforms that can emanate from a singular genetic locus, thereby bolstering proteomic diversity. Perturbations in the regulatory framework of pre-mRNA splicing have been associated with an extensive array of pathological conditions. Oral and maxillofacial morphogenesis, a multifaceted process governed by intricate molecular interactions during embryonic development, is also susceptible to the modulating influence of alternative splicing. Aberrations or dysfunctions in the components responsible for alternative splicing during this critical developmental window can culminate in abnormal craniofacial architectures. In this scholarly review, our emphasis is placed on the exploration of RNA splicing as an emergent feature in oral and maxillofacial development. Importantly, we spotlight instances of splicing dysregulation that contribute to either non-syndromic or syndromic manifestations of cleft palate and enamel developmental anomalies. Deepening our understanding of the role of RNA splicing components and potential downstream effectors in oral and maxillofacial development may provide invaluable insights for prenatal diagnostic modalities.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"145 ","pages":"Article 100900"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144864608","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":"Roles and mechanisms of piRNAs in self-renewal and differentiation of germline stem cells","authors":"Jianchun Zhang ,&nbsp;Xiexin Wang ,&nbsp;Xuanhe Feng ,&nbsp;Yan Chen ,&nbsp;Ke Yu ,&nbsp;Zhiwei Jiang","doi":"10.1016/j.diff.2025.100897","DOIUrl":"10.1016/j.diff.2025.100897","url":null,"abstract":"<div><div>piRNAs are considered to be plentiful and heterogeneous non-coding RNAs, playing a significant role in embryonic patterning and stem cells. In recent research, scientists have explored how piRNAs contribute to both biological processes and roles in stem cells. Their regulatory action is essential for enabling stem cells to both renew themselves and differentiate into specialized types. piRNAs mediate transposable element (TE) silencing to ensure gene integrity via epigenetic repression mechanisms, ‘ping-pong’ mechanism, and splicing. Recent findings reveal that piRNAs are involved in silencing TE and regulating protein-coding mRNAs. This regulation suppresses the target mRNAs either via cleavage mediated by PIWI proteins or through recruiting the CCR4-NOT complex. Thereby the processes of stem cell self-renewal and differentiation have been lightened. piRNAs together with PIWI proteins contribute to controlling the translation of factors. As biological translation regulators, piRNAs in germline stem cells (GSCs) can trigger cell fate by specific regulation of mRNA targets. This role of piRNAs in regulating translation appears to be conserved across stem cells and is likely essential for maintaining stem cell balance. Furthermore, piRNAs along with PIWI proteins can be the biomarkers of stem cells. This review concentrates on recent findings that explore the developmental and biological functions of piRNAs, with a particular emphasis on their contributions to early embryonic organization and the regulation of stem cell behavior.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"145 ","pages":"Article 100897"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763779","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":"WNT7A","authors":"Naomi M. Calhoun,&nbsp;Richard R. Behringer","doi":"10.1016/j.diff.2025.100899","DOIUrl":"10.1016/j.diff.2025.100899","url":null,"abstract":"<div><div>WNT7A regulates numerous developmental processes. It can activate canonical and non-canonical signaling depending on context. It is expressed in the developing central nervous system, limb buds, reproductive organs, and other tissues. Spontaneous and targeted <em>Wnt7a</em> mutations in mouse models resulted in abnormal limbs, defects in male and female reproductive tract organs, infertility, and defects in cerebellar axon remodeling. In zebrafish, <em>wnt7aa</em> mutants exhibited neurogenesis and angiogenesis defects in the central nervous system. In humans, recessive <em>WNT7A</em> missense and nonsense mutations resulted in severe limb and pelvic bone defects. Alterations in <em>WNT7A</em> expression correlated with multiple types of cancer.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"145 ","pages":"Article 100899"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144841502","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":"Bdnf and Ntrk2 functions promote but are not essential for spinal cord myelination in larval zebrafish","authors":"Kristen Russell ,&nbsp;Christina A. Kearns ,&nbsp;Macie B. Walker ,&nbsp;Christopher S. Knoeckel ,&nbsp;Angeles B. Ribera ,&nbsp;Caleb A. Doll ,&nbsp;Bruce Appel","doi":"10.1016/j.diff.2025.100896","DOIUrl":"10.1016/j.diff.2025.100896","url":null,"abstract":"<div><div>Myelin, a specialized membrane produced by oligodendroglial cells in the central nervous system, wraps axons to enhance conduction velocity and maintain axon health. Not all axons are myelinated, and not all myelinated axons are uniformly wrapped along their lengths. Several lines of evidence indicate that neuronal activity can influence myelination, however, the cellular and molecular mechanisms that mediate communication between axons and oligodendrocytes remain poorly understood. Prior research showed that the neurotrophic growth factor Bdnf and its receptor Ntrk2 promote myelination in rodents, raising the possibility that Bdnf and Ntrk2 convey myelin-promoting signals from neurons to oligodendrocytes. We explored this possibility using a combination of gene expression analyses, gene function tests, and myelin sheath formation assays in zebrafish larvae. Altogether, our data indicate that, although not essential for myelination, Bdnf-Ntrk2 signaling contributes to the timely formation of myelin in the developing zebrafish spinal cord.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"145 ","pages":"Article 100896"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144633198","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":"Mettl3 is required for germline function during Drosophila spermatogenesis","authors":"Alannah Morse,&nbsp;Hailey Kaba,&nbsp;Corinne Leighty,&nbsp;Emily MacLean,&nbsp;Rosemarie Mirabella,&nbsp;Mary Reinaker,&nbsp;Rohan Harris,&nbsp;Jazmyn Moodie,&nbsp;Antonio Rockwell","doi":"10.1016/j.diff.2025.100895","DOIUrl":"10.1016/j.diff.2025.100895","url":null,"abstract":"<div><div>The m⁶A modification is responsible for regulating several aspects of RNA metabolism. The enzyme that catalyzes this modification Mettl3, is highly conserved and required for numerous biological processes such as spermatogenesis. Here we examine the role of Mettl3 in germline function during <em>Drosophila</em> spermatogenesis. We find that depletion of Mettl3 in the germline results in errors in late-stage spermatogenesis, the process known as spermiogenesis. In germline knockdowns, actin cones bound to spermatids fail to remain tightly packed during the individualization process. Issues with actin cone assembly appear to disrupt progression through spermiogenesis resulting in waste bag deficiency, an indicator of abnormal spermatid individualization. These errors result in little to no sperm in seminal vesicles culminating in reduced fertility in germline knockdowns. Furthermore, our findings suggest <em>Hsp60B</em> is misregulated in knockdowns, which potentially explains at least some observed phenotypes. Collectively, the data presented in this investigation suggests Mettl3 has a prominent role in regulating spermatid differentiation during <em>Drosophila</em> spermatogenesis.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"145 ","pages":"Article 100895"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144665708","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}