Differentiation最新文献

{"title":"Shared and individual expression patterns of pluripotency genes in the developing chick embryo during neurulation and beyond","authors":"Jenny Hsin ,&nbsp;Rita M. Yazejian ,&nbsp;Ceren Pajanoja ,&nbsp;Laura Kerosuo","doi":"10.1016/j.diff.2025.100866","DOIUrl":"10.1016/j.diff.2025.100866","url":null,"abstract":"<div><div>The neural crest (NC) is a transient population of pluripotent-like, pleistopotent stem cells that emerges early in vertebrate development. These cells play a pivotal role in generating a diverse array of tissues, including the craniofacial bone and cartilage, the entire peripheral nervous system, melanocytes of the skin, certain cardiac structures, and chromaffin cells of the adrenal medulla, among others. The stem cell potential of neural crest cells (NCCs) has long intrigued developmental biologists, as the NC originates post-gastrulation in the ectoderm, yet NCCs also give rise to derivatives typically associated with mesodermal or endodermal origins. Recent work has shown that NCCs co-express factors known from the core pluripotency complex from the pre-gastrulation stages in the epiblast, which enables their exceptionally high stem cell potential. However, detailed spatiotemporal data on pluripotency factor expression in vertebrate embryos remain limited, and the distinction between the function of co-expression of pluripotency genes versus their individual expression in the developing embryo is not clear. In this study, to elucidate the NCC formation process across axial levels as well as the putative different roles of these stem cell genes during early embryogenesis, we used multi-channel fluorescent in situ hybridization to comprehensively examine the anterior-to-posterior expression of pluripotency factors PouV (Oct4), Nanog, Klf4 and Lin28A in chick embryos across key developmental stages, from Hamburger and Hamilton (HH) stage 5 to stage 14. From head to trunk, we find that while the early ectoderm, including the future epidermis and central nervous system (CNS) domains, in the neural fold stages broadly co-express these genes, their expression profiles differ significantly after neurulation. Nanog expression remains in the hindbrain and vagal migratory NCCs. Klf4 strongly marks the developing floor plate, and Klf4, PouV and Lin28A are expressed also in the neural tube that forms the CNS as well as in the developing somites, implying additional roles for these factors during embryogenesis.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"144 ","pages":"Article 100866"},"PeriodicalIF":2.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144177534","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":"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":"Letter to the Editor regarding: “Fgf8 promotes survival of nephron progenitors by regulating BAX/BAK mediated apoptosis” by Matthew J. Anderson, et al","authors":"Jian Wu ,&nbsp;Wenya Gao ,&nbsp;Ruili Li ,&nbsp;Mingfei Yang","doi":"10.1016/j.diff.2025.100864","DOIUrl":"10.1016/j.diff.2025.100864","url":null,"abstract":"","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"143 ","pages":"Article 100864"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888021","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":"New genetic tools to define the pathophysiology of inborn errors of cobalamin metabolism impacting mammalian development","authors":"Tiffany Chern ,&nbsp;Xuefei Tong ,&nbsp;William G. Bauer ,&nbsp;David J. Quispe-Parra ,&nbsp;Xia Gao ,&nbsp;Kamryn N. Gerner-Mauro ,&nbsp;Ross A. Poché","doi":"10.1016/j.diff.2025.100868","DOIUrl":"10.1016/j.diff.2025.100868","url":null,"abstract":"<div><div>The congenital, autosomal recessive disorder combined methylmalonic acidemia and homocystinuria – <em>cblC</em> type, is the most common inborn error of cobalamin (vitamin B₁₂) metabolism. In its early onset form, <em>cblC</em> profoundly impacts fetal development of the central nervous system, hematopoietic system, and other tissues. Previously, mutations in the <em>MMACHC</em> gene, which encodes a protein required for the intracellular trafficking and enzymatic processing of free cobalamin into active coenzyme forms, were found to cause <em>cblC</em>. These coenzymes are required in two metabolic pathways which produce either succinyl-CoA in the mitochondria or methionine in the cytosol. However, due to a lack of sufficient animal models, the exact pathophysiology of <em>cblC</em> remains unknown. Moreover, there is evidence to suggest that MMACHC may have roles outside of cobalamin metabolism and that cobalamin itself may be required for additional, unknown metabolic pathways. Here, we report the generation and characterization of three new mouse lines aimed at further defining the role of MMACHC and cobalamin in mammalian development. CRISPR/Cas9 genome editing was used to develop an HA-tagged version of <em>Mmachc</em>, which will aid in affinity purification and spatiotemporal localization of the MMACHC protein. To clarify which metabolic perturbations downstream of <em>Mmachc</em> loss give rise to tissue-specific developmental defects, we also created floxed alleles for both methionine synthase <em>(Mtr)</em> and methylmalonyl-CoA mutase <em>(Mmut)</em>, which are the only known cobalamin dependent enzymes in mammals. In total, these new mouse models significantly expand upon the repertoire of genetic reagents to clarify the pathophysiology of <em>cblC</em> as well as define both the canonical and hypothesized noncanonical roles of MMACHC in mammalian development.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"143 ","pages":"Article 100868"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144116295","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}

{"title":"RANKL promotes MT2 degradation and ROS production in osteoclast precursors through Beclin1-dependent autophagy","authors":"Dianshan Ke ,&nbsp;Tingwei Gao ,&nbsp;Hanhao Dai ,&nbsp;Jie Xu,&nbsp;Tie Ke","doi":"10.1016/j.diff.2025.100863","DOIUrl":"10.1016/j.diff.2025.100863","url":null,"abstract":"<div><div>ROS produced under oxidative stress are crucial for osteoclast differentiation. Metallothionein (MT) is a ROS-scavenging molecule. As a member of MT family, MT2 can clear ROS in osteoclast precursors (OCPs) and contributes to osteoclast differentiation. RANKL can promote OCP autophagy. Given the molecular-degrading effect of autophagy, the relationship between RANKL-dependent autophagy, MT2 and ROS during osteoclast differentiation is worth exploring. We depended <em>in vitro</em> RANKL administration and RANKL-overexpressing (Tg-RANKL) mice to observe the effects of RANKL on ROS production, MT2 protein expression, Beclin1 expression and autophagic activity in OCPs. Spautin1 was used to investigate the relationship between Beclin1-dependent autophagy and RANKL-regulated MT2 expression. Osteoclast-targeting MT2-cDNA-AAVs were applied to assess the therapeutic effect of MT2 on Tg-RANKL-related bone loss. The results showed that RANKL promoted ROS production but reduced MT2 protein expression in OCPs. RANKL also enhanced Beclin1 expression and LC3-puncta abundance. Decreased Beclin1 expression with spautin1 blocked RANKL-increased ROS production and osteoclast differentiation and recovered RANKL-decreased MT2 expression. MT2 selective overexpression with CD11b-promoter-MT2-cDNA-AAVs attenuated ROS production and osteoclastogenesis in Tg-RANKL mice and improved bone loss. Overall, RANKL can reduce MT2 protein expression through Beclin1-dependent autophagy, thereby promoting ROS production and osteoclast differentiation; this suggests that MT2-overexpressing small molecule drugs have the potential to treat RANKL-related bone loss.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"143 ","pages":"Article 100863"},"PeriodicalIF":2.2,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855973","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":"The mechanism of EGF in promoting skeletal muscle post-injury regeneration","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.2025.100862","DOIUrl":"10.1016/j.diff.2025.100862","url":null,"abstract":"<div><div>Epidermal Growth Factor (EGF) is a multifunctional cytokine that plays an important role in the growth and development of skeletal muscle. In this study, a mouse skeletal muscle post-injury regeneration model and the C2C12 myoblasts cell line were used to elucidate the molecular mechanism by which EGF promotes myoblast proliferation and differentiation and then improves skeletal muscle post-injury regeneration. EGF regulates the activities of p38-MAPK and PI3K/AKT/mTOR signaling pathways through the Epidermal Growth Factor Receptor (EGFR), thereby promoting the proliferation and differentiation of myoblasts. This finding will support the treatment of skeletal muscle injury, which is of great value in resolving muscle health problems such as muscular atrophy and sarcopenia.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"143 ","pages":"Article 100862"},"PeriodicalIF":2.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835039","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":"Chondrocalcin: Insights into its regulation and multi-function in cartilage and bone","authors":"Wensha Zhu ,&nbsp;Zilong Zhao ,&nbsp;Weigang Yuwen ,&nbsp;Linlin Qu ,&nbsp;Zhiguang Duan ,&nbsp;Chenhui Zhu ,&nbsp;Daidi Fan","doi":"10.1016/j.diff.2025.100861","DOIUrl":"10.1016/j.diff.2025.100861","url":null,"abstract":"<div><div>Type Ⅱ collagen (COLⅡ) is the primary constituent of the cartilage matrix, specifically present in vitreous bodies, cartilage, bone, and other skeletal elements. Therefore, the normal expression of COLⅡ is crucial for the normal development, linear growth, mechanical properties, and self-repairing ability of cartilage. Chondrocalcin, the C-propeptide of type Ⅱ procollagen, is not only a marker of COLⅡ synthesis but also one of the most abundant polypeptides in cartilage. This work examines the pivotal role of chondrocalcin in the synthesis of COLⅡ, comprehensively examining its regulation and multi-functions in cartilage and bone related diseases. Our findings suggest that mutations in the chondrocalcin-encoding domain of <em>COL2A1</em> affect cartilage and bone development in clinical conditions.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"143 ","pages":"Article 100861"},"PeriodicalIF":2.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725945","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}