Differentiation最新文献

{"title":"Regulation of trophectoderm morphogenesis by small GTPase RHOA through HIPPO signaling-dependent and -independent mechanisms in mouse preimplantation development","authors":"Yusuke Marikawa,&nbsp;Vernadeth B. Alarcon","doi":"10.1016/j.diff.2025.100835","DOIUrl":"10.1016/j.diff.2025.100835","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"141 ","pages":"Article 100835"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","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":"NEDD4's effect on osteoblastogenesis potential of bone mesenchymal stem cells in rats concerned with PI3K/Akt pathway","authors":"Bo Li ,&nbsp;Shuang Zhang ,&nbsp;Xiaoxian Yun ,&nbsp;Chengyi Liu ,&nbsp;Rui Xiao ,&nbsp;Mingjie Lu ,&nbsp;Xiaomei Xu ,&nbsp;Fuwei Lin","doi":"10.1016/j.diff.2024.100830","DOIUrl":"10.1016/j.diff.2024.100830","url":null,"abstract":"<div><div>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.</div><div>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.</div><div>These findings suggest that NEDD4 may inhibit BMSCs differentiation by suppressing the PI3K/Akt pathway during osteogenesis.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"141 ","pages":"Article 100830"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","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":"OA","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 ,&nbsp;Jiaoyan Wu ,&nbsp;Jiayi Chang ,&nbsp;Haoyuan Peng ,&nbsp;Zitao Liu ,&nbsp;Pengfei Liu ,&nbsp;Xu Han ,&nbsp;Tiantian Sun ,&nbsp;Dandan Shang ,&nbsp;Yutian Yang ,&nbsp;Zhihao Li ,&nbsp;Pengkun Li ,&nbsp;Yixuan Liu ,&nbsp;Yonghao Zhu ,&nbsp;Yunzhi Lv ,&nbsp;Xiumei Guo ,&nbsp;Ying Zhao ,&nbsp;Yang An","doi":"10.1016/j.diff.2024.100832","DOIUrl":"10.1016/j.diff.2024.100832","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"141 ","pages":"Article 100832"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","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":"SMAD2/3 signaling determines the colony architecture in a hydrozoan, Dynamena pumila","authors":"Alexandra A. Vetrova ,&nbsp;Stanislav V. Kremnyov","doi":"10.1016/j.diff.2025.100834","DOIUrl":"10.1016/j.diff.2025.100834","url":null,"abstract":"<div><div>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 <em>Hydra</em>. 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 <em>Dynamena pumila,</em> 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 <em>D. pumila</em> primary colony, resembling naturally occurring malformation. Additionally, we identified a <em>Nodal-related</em> gene in <em>D. pumila</em> 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.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"141 ","pages":"Article 100834"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","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":"Cspg4 sculpts oligodendrocyte precursor cell morphology","authors":"Samantha Bromley-Coolidge,&nbsp;Diego Iruegas,&nbsp;Bruce Appel","doi":"10.1016/j.diff.2024.100819","DOIUrl":"10.1016/j.diff.2024.100819","url":null,"abstract":"<div><div>The extracellular matrix (ECM) provides critical biochemical and structural cues that regulate neural development. Chondroitin sulfate proteoglycans (CSPGs), a major ECM component, have been implicated in modulating oligodendrocyte precursor cell (OPC) proliferation, migration, and maturation, but their specific roles in oligodendrocyte lineage cell (OLC) development and myelination <em>in vivo</em> remain poorly understood. Here, we use zebrafish as a model system to investigate the spatiotemporal dynamics of ECM deposition and CSPG localization during central nervous system (CNS) development, with a focus on their relationship to OLCs. We demonstrate that ECM components, including CSPGs, are dynamically expressed in distinct spatiotemporal patterns coinciding with OLC development and myelination. We found that zebrafish lacking <em>cspg4</em> function produced normal numbers of OLCs, which appeared to undergo proper differentiation. However, OPC morphology in mutant larvae was aberrant. Nevertheless, the number and length of myelin sheaths produced by mature oligodendrocytes were unaffected. These data indicate that <em>Cspg4</em> regulates OPC morphogenesis <em>in vivo</em>, supporting the role of the ECM in neural development.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"140 ","pages":"Article 100819"},"PeriodicalIF":2.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683463","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":"A primer on the pleiotropic endocrine fibroblast growth factor FGF19/FGF15","authors":"Agathe Bouju ,&nbsp;Roel Nusse ,&nbsp;Peng V. Wu","doi":"10.1016/j.diff.2024.100816","DOIUrl":"10.1016/j.diff.2024.100816","url":null,"abstract":"<div><div>Fibroblast Growth Factor 19 (FGF19) is a member of the Fibroblast Growth Factor (FGF) family, known for its role in various cellular processes including embryonic development and metabolic regulation. FGF19 functions as an endocrine factor, influencing energy balance, bile acid synthesis, glucose and lipid metabolism, as well as cell proliferation. FGF19 has a conserved structure typical of FGFs but exhibits unique features. Unlike most FGFs, which act locally, FGF19 travels through the bloodstream to distant targets including the liver. Its interaction with the β-Klotho (KLB) co-receptor and FGF Receptor 4 (FGFR4) in hepatocytes or FGFR1c in extrahepatic tissues initiates signaling cascades crucial for its biological functions. Although the mouse ortholog, FGF15, diverges significantly from human FGF19 in protein sequence and receptor binding, studies of FGF15-deficient mice have led to a better understanding of the proteins’ role in bile acid regulation, metabolism, and embryonic development. Overexpression studies in transgenic mice have further revealed roles in not only ameliorating metabolic diseases but also in promoting hepatocyte proliferation and tumorigenesis. This review summarizes the gene and protein structure of FGF19/15, its expression patterns, phenotypes in mutant models, and implication in human diseases, providing insights into potential therapeutic strategies targeting the FGF19 signaling pathway.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"140 ","pages":"Article 100816"},"PeriodicalIF":2.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A primer for Fibroblast Growth Factor 16 (FGF16)","authors":"Diana Rigueur","doi":"10.1016/j.diff.2024.100817","DOIUrl":"10.1016/j.diff.2024.100817","url":null,"abstract":"<div><div>During the discovery of the Fibroblast Growth Factor superfamily, scientists were determined to uncover all the genes that encoded FGF proteins. In 1998, <em>FGF16</em> was discovered with classical cloning techniques in human and rat heart samples. <em>FGF16</em> loss- and gain-of-function experiments in several organisms demonstrated a conserved function in vertebrates, and as a component of the FGF9 subfamily of ligands (FGF-E/-9/-20), is functionally conserved and sufficient to rescue loss-of-function phenotypes in invertebrates, like <em>C. elegans</em>. <em>FGF16</em> has a broad expression pattern, predominantly expressed in brown adipose tissue, heart, with low but detectable levels in the brain, olfactory bulb, inner ear, muscle, thymus, pancreas, spleen, stomach, small intestine, and gonads (testis and ovary). FGF16 is also expressed moderately in the late developing limb bud. Despite its expression levels, this ligand plays notable roles in autopod metacarpal development; loss of one allele causes congenital metacarpal 4–5 fusion and hand deformities in humans. The broad expression pattern of <em>FGF16</em> in several tissues underscores its multifaceted roles in stem cell maintenance, proliferation, cell fate specification, and metabolism.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"140 ","pages":"Article 100817"},"PeriodicalIF":2.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo movement of retinoblastoma-related protein (RBR) towards cytoplasm during mitosis in Arabidopsis thaliana","authors":"Sergio Miguel-Hernández ,&nbsp;Estephania Zluhan-Martínez ,&nbsp;Adriana Garay-Arroyo ,&nbsp;Lourdes Cabrera-Muñoz ,&nbsp;Adriana Hernández-Angeles ,&nbsp;Noé Valentín Durán-Figueroa ,&nbsp;Vadim Pérez-Koldenkova ,&nbsp;M. Verónica Ponce-Castañeda","doi":"10.1016/j.diff.2024.100800","DOIUrl":"10.1016/j.diff.2024.100800","url":null,"abstract":"<div><div><span><span><span>Retinoblastoma protein<span> is central in signaling networks of fundamental cell decisions such as proliferation and differentiation in all metazoans and cancer development. </span></span>Immunostaining and biochemical evidence demonstrated that during </span>interphase retinoblastoma protein is in the nucleus and is hypophosphorylated, and during mitosis is in the cytoplasm and is hyperphosphorylated. The purpose of this study was to visualize </span><em>in vivo</em><span> in a non-diseased tissue, the dynamic spatial and temporal nuclear exit toward the cytoplasm of this protein during mitosis and its return to the nucleus to obtain insights into its potential cytosolic functions. Using high-resolution time-lapse images from confocal microscopy, we tracked </span><em>in vivo</em><span> the ortholog in plants the RETINOBLASTOMA RELATED (RBR) protein tagged with Green Fluorescent Protein (GFP) in </span><span><span>Arabidopsis thaliana</span></span><span><span>'s root. RBR protein exits from dense aggregates in the nucleus before chromosomes are in </span>prophase<span> in less than 2 min, spreading outwards as smaller particles projected throughout the cytosol during mitosis like a diffusive yet controlled event until telophase<span>, when the daughter's nuclei form; RBR returns to the nuclei in coordination with decondensing chromosomal DNA forming new aggregates again in punctuated larger structures in each corresponding nuclei. We propose RBR diffused particles in the cytoplasm may function as a cytosolic sensor of incoming signals, thus coordinating re-aggregation with DNA is a mechanism by which any new incoming signals encountered by RBR may lead to a reconfiguration of the nuclear transcriptomic context. The small RBR diffused particles in the cytoplasm may preserve topologic-like properties allowing them to aggregate and restore their nuclear location, they may also be part of transient cytoplasmic storage of the cellular pre-mitotic transcriptional context, that once inside the nuclei may execute both the pre mitosis transcriptional context as well as new transcriptional instructions.</span></span></span></div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"140 ","pages":"Article 100800"},"PeriodicalIF":2.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581446","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":"Fgf17: A regulator of the mid/hind brain boundary in mammals","authors":"Zane Oberholzer,&nbsp;Chiron Loubser,&nbsp;Natalya V. Nikitina","doi":"10.1016/j.diff.2024.100813","DOIUrl":"10.1016/j.diff.2024.100813","url":null,"abstract":"<div><div>The Fibroblast growth factor (FGFs) family consists of at least 22 members that exert their function by binding and activating fibroblast growth factor receptors (FGFRs). The <em>Fgf8/FgfD</em> subfamily member, <em>Fgf17</em>, is located on human chromosome 8p21.3 and mouse chromosome 14 D2. In humans, FGF17 can be alternatively spliced to produce two isoforms (FGF17a and b) whereas three isoforms are present in mice (Fgf17a, b, and c), however, only Fgf17a and Fgf17b produce functional proteins. Fgf17 is a secreted protein with a cleavable N-terminal signal peptide and contains two binding domains, namely a conserved core region and a heparin binding site. <em>Fgf1</em>7 mRNA is expressed in a wide range of different tissues during development, including the rostral patterning centre, midbrain-hindbrain boundary, tailbud mesoderm, olfactory placode, mammary glands, and smooth muscle precursors of major arteries. Given its broad expression pattern during development, it is surprising that adult <em>Fgf17</em>^{<em>−/−</em>} mice displayed a rather mild phenotype; such that mutants only exhibited morphological changes in the frontal cortex and mid/hind brain boundary and changes in certain social behaviours. In humans, <em>FGF17</em> mutations are implicated in several diseases, including Congenital Hypogonadotropic Hypogonadism and Kallmann Syndrome. <em>FGF17</em> mutations contribute to CHH/KS in 1.1% of affected individuals, often presenting in conjunction with mutations in other <em>FGF</em> pathway genes like <em>FGFR1</em> and <em>FLRT3</em>. <em>FGF17</em> mutations were also identified in patients diagnosed with Dandy-Walker malformation and Pituitary Stalk Interruption Syndrome, however, it remains unclear how <em>FGF17</em> is implicated in these diseases. Altered <em>FGF17</em> expression has been observed in several cancers, including prostate cancer, hematopoietic cancers (acute myeloid leukemia and acute lymphoblastic leukemia), glioblastomas, perineural invasion in cervical cancer, and renal cell carcinomas. Furthermore, FGF17 has demonstrated neuroprotective effects, particularly during ischemic stroke, and has been shown to improve cognitive function in ageing mice.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"140 ","pages":"Article 100813"},"PeriodicalIF":2.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RUNX2 regulation in osteoblast differentiation: A possible therapeutic function of the lncRNA and miRNA-mediated network","authors":"Pakkath Narayanan Arya,&nbsp;Iyyappan Saranya,&nbsp;Nagarajan Selvamurugan","doi":"10.1016/j.diff.2024.100803","DOIUrl":"10.1016/j.diff.2024.100803","url":null,"abstract":"<div><div>Osteogenic differentiation is a crucial process in the formation of the skeleton and the remodeling of bones. It relies on a complex system of signaling pathways and transcription factors, including Runt-related transcription factor 2 (RUNX2). Non-coding RNAs (ncRNAs) control the bone-specific transcription factor RUNX2 through post-transcriptional mechanisms to regulate osteogenic differentiation. The most research has focused on microRNAs (miRNAs) and long ncRNAs (lncRNAs) in studying how they regulate RUNX2 for osteogenesis in both normal and pathological situations. This article provides a concise overview of the recent advancements in understanding the critical roles of lncRNA/miRNA/axes in controlling the expression of RUNX2 during bone formation. The possible application of miRNAs and lncRNAs as therapeutic agents for the treatment of disorders involving the bones and bones itself is also covered.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"140 ","pages":"Article 100803"},"PeriodicalIF":2.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141848584","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}