Differentiation最新文献

{"title":"NOTCH1, 2, and 3 receptors enhance osteoblastogenesis of mesenchymal C3H10T1/2 cells and inhibit this process in preosteoblastic MC3T3-E1 cells.","authors":"Jose-Luis Resuela-González, María-Julia González-Gómez, María-Milagros Rodríguez-Cano, Susana López-López, Eva-María Monsalve, María-José M Díaz-Guerra, Jorge Laborda, María-Luisa Nueda, Victoriano Baladrón","doi":"10.1016/j.diff.2025.100837","DOIUrl":"https://doi.org/10.1016/j.diff.2025.100837","url":null,"abstract":"<p><p>Osteoblastogenesis is governed by complex interplays among signaling pathways, which modulate the expression of specific markers at each differentiation stage. This process enables osteoblast precursor cells to adopt the morphological and biochemical characteristics of mature bone cells. Our study investigates the role of NOTCH signaling in osteogenesis in MC3T3-E1 and C3H10T1/2 cell lines. MC3T3-E1 cells are preosteoblast precursors widely recognized as a model for bone biology research, offering a convenient and physiologically relevant system to study osteoblast transcriptional regulation. Conversely, the mesenchymal C3H10T1/2 cells are multipotent, capable of differentiating into osteoblasts, adipocytes, and chondrocytes under specific extracellular cues. The core of this in vitro study is the comparative analysis of the impact of overexpressing each mammalian NOTCH receptor on osteoblastogenesis in two cell lines reflecting different cell differentiation stages. We generated stable transfectant pools of both cell lines for each of the four NOTCH receptors and characterized their effect on osteoblastogenesis. We successfully obtained transfectant pools that overexpress Notch1, Notch2 and Notch3 at both mRNA and protein levels. However, we were unable to obtain cells overexpressing Notch4 at protein level. Our findings reveal that the overexpression of NOTCH1, NOTCH2, and NOTCH3 receptors promotes osteoblast differentiation in mesenchymal C3H10T1/2 cells, while inhibiting it in preosteoblastic MC3T3-E1 cells. These results provide novel insights into the distinct roles of NOTCH receptors in osteoblastogenesis across two different precursor cell types, potentially guiding the development of new therapeutic approaches for bone diseases.</p>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"142 ","pages":"100837"},"PeriodicalIF":2.2,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069356","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":"Delamination of chick cephalic neural crest cells requires an MMP14-dependent downregulation of Cadherin-6B.","authors":"Cyril Andrieu, Cathy Danesin, Audrey Montigny, Marie Rey, Klara Baqué, Anne Bibonne, Dominique Alfandari, Eric Theveneau","doi":"10.1016/j.diff.2025.100836","DOIUrl":"https://doi.org/10.1016/j.diff.2025.100836","url":null,"abstract":"<p><p>Matrix Metalloproteinases (MMPs) are known for their role in matrix remodeling via their catalytic activities in the extracellular space. Interestingly, these enzymes can also play less expected roles in cell survival, polarity and motility via other substrates (e.g. receptors, chemokines), through an intracellular localization (e.g. the nucleus) or via non-catalytic functions. Most of these unconventional functions are yet to be functionally validated in a physiological context. Here, we used the delamination of the cephalic Neural Crest (NC) cells of the chicken embryo, a well described experimental model of epithelial-mesenchymal transition (EMT), to study the in vivo function of MMP14 (a.k.a MT1-MMP). MMP14 is a transmembrane MMP known for its importance in cell invasion and often associated with poor prognosis in cancer. We found that MMP14 is expressed and required for cephalic NC delamination. More specifically, MMP14 is necessary for the downregulation of Cadherin-6B and a co-inhibition of Cadherin-6B and MMP14 expressions is sufficient to restore NC delamination. Cadherin-6B is normally repressed by Snail2. Surprisingly, in MMP14 knockdown this lack of Cadherin-6B repression occurs in the context of a normal expression and nuclear import of Snail2. We further show that MMP14 is not detected in the nucleus and that Snail2 and MMP14 do not physically interact. These data reveals that a yet to be identified MMP14-dependent signaling event is required for the Snail2-dependent repression of Cadherin-6B. In conclusion, this work provides an in vivo example of atypical regulation of Cadherins by an MMP which emphasizes the importance and diversity of non-canonical functions of MMPs.</p>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":" ","pages":"100836"},"PeriodicalIF":2.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015571","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":"Regulation of trophectoderm morphogenesis by small GTPase RHOA through HIPPO signaling-dependent and -independent mechanisms in mouse preimplantation development.","authors":"Yusuke Marikawa, Vernadeth B Alarcon","doi":"10.1016/j.diff.2025.100835","DOIUrl":"https://doi.org/10.1016/j.diff.2025.100835","url":null,"abstract":"<p><p>The trophectoderm (TE) is the first tissue to differentiate during the preimplantation development of the mammalian embryo. It forms the outer layer of the blastocyst and is responsible for generating the blastocoel, a fluid-filled cavity whose expansion is essential for successful hatching and implantation. Here, we investigated the role of the small GTPase RHOA in the morphogenesis of the TE, particularly its relationship with HIPPO signaling, using mouse embryos as a model. Inhibition of RHOA resulted in the failure to form a blastocoel and significantly altered the expression of numerous genes. Transcriptomic analysis revealed that 330 genes were down-regulated and 168 genes were up-regulated by more than two-fold. Notably, 98.4% of these transcriptional changes were reversed by simultaneous inhibition of LATS kinases, indicating that the transcriptional influence of RHOA is primarily mediated through HIPPO signaling. Many of the down-regulated genes are involved in critical processes of TE morphogenesis, such as apical-basal cell polarization, tight junction formation, and sodium and water transport, suggesting that RHOA supports TE development by enhancing the expression of morphogenesis-related genes through HIPPO signaling, specifically via TEAD transcription factors. However, RHOA inhibition also disrupted apical-basal polarity and tight junctions, effects that were not restored by LATS inhibition, pointing to additional HIPPO signaling-independent mechanisms by which RHOA controls TE morphogenesis. Furthermore, RHOA inhibition impaired cell viability at the late blastocyst stage, with partial rescue observed upon LATS inhibition, suggesting that RHOA maintains cell survival through both HIPPO signaling-dependent and -independent pathways. A deeper knowledge of the molecular mechanisms governing TE morphogenesis, including blastocoel expansion and cell viability, could significantly advance assisted reproductive technologies aimed at producing healthy blastocysts.</p>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"141 ","pages":"100835"},"PeriodicalIF":2.2,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061334","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":"SMAD2/3 signaling determines the colony architecture in a hydrozoan, Dynamena pumila.","authors":"Alexandra A Vetrova, Stanislav V Kremnyov","doi":"10.1016/j.diff.2025.100834","DOIUrl":"https://doi.org/10.1016/j.diff.2025.100834","url":null,"abstract":"<p><p>Most hydrozoan cnidarians form complex colonies that vary in size, shape, and branching patterns. However, little is known about the molecular genetic mechanisms responsible for the diversity of the hydrozoan body plans. The Nodal signaling pathway has previously been shown to be essential for setting up a new body axis in a budding Hydra. This budding process is often compared to the branching of colonial hydrozoans, suggesting that the signaling mechanisms underlying branching and budding are evolutionarily conserved. Using the colonial hydrozoan Dynamena pumila, we demonstrated that colony architecture depends on the activity level of SMAD2/3-mediated signaling. Pharmacological inhibition of the SMAD2/3-mediated Nodal signaling pathway resulted in an altered architecture of D. pumila primary colony, resembling naturally occurring malformation. Additionally, we identified a Nodal-related gene in D. pumila and observed its expression at the earliest stage of new colony module formation. Taken together, our results suggest that TGF-β signaling pathway plays an important role in shaping the morphology of hydrozoan colony.</p>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"141 ","pages":"100834"},"PeriodicalIF":2.2,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015525","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":"WNT16 primer.","authors":"McLean H Williamson, Wilson K Clements","doi":"10.1016/j.diff.2024.100833","DOIUrl":"https://doi.org/10.1016/j.diff.2024.100833","url":null,"abstract":"","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":" ","pages":"100833"},"PeriodicalIF":2.2,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900048","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":"Deciphering endocrine function of adipose tissue and its significant influences in obesity-related diseases caused by its dysfunction.","authors":"Feiyi Duan, Jiaoyan Wu, Jiayi Chang, Haoyuan Peng, Zitao Liu, Pengfei Liu, Xu Han, Tiantian Sun, Dandan Shang, Yutian Yang, Zhihao Li, Pengkun Li, Yixuan Liu, Yonghao Zhu, Yunzhi Lv, Xiumei Guo, Ying Zhao, Yang An","doi":"10.1016/j.diff.2024.100832","DOIUrl":"https://doi.org/10.1016/j.diff.2024.100832","url":null,"abstract":"<p><p>Current research has found that adipose tissue is not only involved in energy metabolism, but also a highly active endocrine organ that secretes various adipokines, including adiponectin, leptin, resistin and apelin, which are involved in the regulation of physiology and pathology of tissues and organs throughout the body. With the yearly increasing incidence, obesity has become a risk factor for a variety of pathological changes, including inflammation and metabolic syndrome in various system (endocrine, circulatory, locomotor and central nervous system). Thus these symptoms lead to multi-organ dysfunctions, including the heart, liver, kidneys, brain and joints. An in-depth summary of the roles of adipokines in the regulation of other tissues and organs can help to provide more effective therapeutic strategies for obesity-related diseases and explore potential therapeutic targets. Therefore, this review has retrospected the endocrine function of adipose tissue under obesity and the role of dysregulated adipokine secretion in related diseases and the underlying mechanisms, in order to provide a theoretical basis for targeting adipokine-mediated systemic dysregulation.</p>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"141 ","pages":"100832"},"PeriodicalIF":2.2,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878121","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":"NEDD4's effect on osteoblastogenesis potential of bone mesenchymal stem cells in rats concerned with PI3K/Akt pathway.","authors":"Bo Li, Shuang Zhang, Xiaoxian Yun, Chengyi Liu, Rui Xiao, Mingjie Lu, Xiaomei Xu, Fuwei Lin","doi":"10.1016/j.diff.2024.100830","DOIUrl":"https://doi.org/10.1016/j.diff.2024.100830","url":null,"abstract":"<p><p>Neural precursor cell expressed developmentally down-regulated 4 (NEDD4) is an E3 ubiquitin ligase implicated in craniofacial development. Emerging evidence suggests that NEDD4 may down-regulates Akt signaling, a key element of the PI3K/Akt pathway involved in cell differentiation. This study aimed to investigate NEDD4's role in bone mesenchymal stem cells (BMSCs) differentiation and its interaction with the PI3K/Akt pathway. BMSCs were isolated from SD rats, and NEDD4 expression increased during osteogenic differentiation. Silencing NEDD4 with siRNA elevated alkaline phosphatase (ALP), osteocalcin (OCN), Akt, and mTORC1 expression during induction, while subsequent treatment with LY294002 (a broad spectrum PI3K inhibitor) reduced Akt, mTORC1, ALP, and OCN levels. These findings suggest that NEDD4 may inhibit BMSCs differentiation by suppressing the PI3K/Akt pathway during osteogenesis.</p>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"141 ","pages":"100830"},"PeriodicalIF":2.2,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824782","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":"Dissecting the role of vitamin B₁₂ metabolism in craniofacial development through analysis of clinical phenotypes and model organism discoveries.","authors":"Briana E Pinales, Carlos E Palomino, German Rosas-Acosta, Giulio Francia, Anita M Quintana","doi":"10.1016/j.diff.2024.100831","DOIUrl":"https://doi.org/10.1016/j.diff.2024.100831","url":null,"abstract":"<p><p>Vitamin B₁₂, otherwise known as cobalamin, is an essential water-soluble vitamin that is obtained from animal derived dietary sources. Mutations in the genes that encode proteins responsible for cobalamin uptake, transport, or processing cause inborn errors of cobalamin metabolism, a group of disorders characterized by accumulation of homocysteine and methylmalonic acid, neurodevelopmental defects, ocular dysfunction, anemia, and failure to thrive. Mild to moderate craniofacial phenotypes have been observed but these phenotypes are not completely penetrant and have not been consistently recognized in the literature. However, in the most recent decade, animal models of cblX and cblC, two cobalamin disorder complementation groups, have documented craniofacial phenotypes. These data indicate a function for cobalamin in facial development. In this review, we performed a literature review of all cobalamin complementation groups to identify which groups, and which human variants, are associated with dysmorphic features, microcephaly, or marfanoid phenotypes. We identified dysmorphic facial features in cblC, cblX, cblG, cblF, and cblJ, which are caused by mutations in MMACHC, HCFC1, MTR, LMBRD1, and ABCD4, respectively. Other complementation groups were associated primarily with microcephaly. Animal models (zebrafish and mouse) of cblC and cblX support these clinical phenotypes and have demonstrated neural crest cell deficits that include reduced expression of prdm1a, sox10, and sox9, key molecular markers of neural crest development. Characterization of a zebrafish mmachc germline mutant also suggests atypical chondrocyte development. Collectively, these data demonstrate an essential role for cobalamin in facial development and warrant future mechanistic inquiries that dissect the cellular and molecular mechanisms underlying human facial phenotypes in cobalamin disorders.</p>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":" ","pages":"100831"},"PeriodicalIF":2.2,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830765","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":"Divergent functions of the evolutionarily conserved, yet seemingly dispensable, Wnt target, sp5.","authors":"Saurav Mohanty, Arne C Lekven","doi":"10.1016/j.diff.2024.100829","DOIUrl":"https://doi.org/10.1016/j.diff.2024.100829","url":null,"abstract":"<p><p>The activation of sp5 in response to Wnt/β-catenin signaling is observed in many species during axis patterning, neural crest induction, maintenance and differentiation of stem cells. Indeed, the conserved response of sp5 orthologs to Wnt-mediated activation is the basis for this gene commonly being used as a readout for Wnt signaling activity. However, several seemingly conflicting findings regarding the function of sp5 in the context of Wnt signaling cast this gene in an enigmatic light. In this review, we examine current knowledge of sp5 structure and function, its relationship to Wnt signaling in varied contexts, and present perspectives on how progress on this interesting gene can move forward.</p>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"141 ","pages":"100829"},"PeriodicalIF":2.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830766","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":"WNT9A and WNT9B in Development and Disease.","authors":"Amber D Ide, Stephanie Grainger","doi":"10.1016/j.diff.2024.100820","DOIUrl":"10.1016/j.diff.2024.100820","url":null,"abstract":"<p><p>WNT9 paralogues, WNT9A and WNT9B, are secreted ligands driving both the canonical (β-catenin dependent) and non-canonical (β-catenin independent) Wnt signaling pathways. These pathways play roles in cell fate determination, embryonic patterning, bone development, and organogenesis, among other biological processes. Studies of Wnt9a and Wnt9b mutant animals demonstrate that they have specific and overlapping roles in these processes. Wnt9a is critical in directing stem and progenitor cell fate during hematopoietic stem cell development, proper bone formation, and chondrogenesis, while Wnt9b is important for kidney and heart development. Both proteins are essential in craniofacial development and convergent extension movements. Dysregulated expression of human WNT9A and WNT9B have been implicated in different cancers and disease, suggesting these proteins or their downstream pathways may represent potential therapeutic targets.</p>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":" ","pages":"100820"},"PeriodicalIF":2.2,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774330","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}