Differentiation最新文献

{"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}

{"title":"Fibroblast Growth Factor (FGF) 13","authors":"Lucia J. Rivas ,&nbsp;Rosa A. Uribe","doi":"10.1016/j.diff.2024.100814","DOIUrl":"10.1016/j.diff.2024.100814","url":null,"abstract":"<div><div>Fibroblast Growth Factor (FGF) 13, also referred to as FGF homologous factor (FHF) 2, is a member of the FGF11 subfamily that is characterized as having sequence similarities to classical FGF receptor (FGFR)-binding FGFs, but functionally do not bind FGFRs. In this primer mini-review, we summarize current knowledge regarding FGF13 expression, mutant analyses, and gene and protein structure. Similar to other FHFs, FGF13 has been considered a non-secreted protein that lacks an amino signal and is prominently expressed in developing and mature neurons of the central and peripheral nervous systems, as well as the heart. The expression of FGF13 is not limited to early embryonic stages and has been shown to persist in adult tissues. As well, FGF13 is known to localize subcellularly, both within the cytoplasm and the nucleus. FGF13 is extremely adaptable, as it interacts with MAPK scaffolding protein islet brain 2 (IB2), stabilizes microtubules, or binds to voltage-gated sodium channels. <em>Fgf13</em> mutant mouse lines display various neurological pathologies. Through sequence mapping, <em>FGF13</em> is considered a candidate causative gene that is mutated in multiple human X-linked neurological diseases.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"140 ","pages":"Article 100814"},"PeriodicalIF":2.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331691","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":"Redefining retinoic acid receptor expression in zebrafish embryos using Hybridization Chain Reaction","authors":"Raèden Gray,&nbsp;C. Ben Lovely","doi":"10.1016/j.diff.2024.100822","DOIUrl":"10.1016/j.diff.2024.100822","url":null,"abstract":"<div><div>Retinoic Acid (RA) is the key signaling molecule during embryonic development with the RA pathway playing multiple roles in throughout development. Previous work has shown RA signaling to be key in development of the craniofacial skeleton. RA signaling is driven by RA binding to the nuclear transcription factors, retinoic acid receptor (RAR) and retinoic X receptor (RXR). RARs and RXR heterodimerize to bind specific DNA sequences known as retinoic acid response elements or RAREs. Though the genes that code for these receptors are known to be involved during craniofacial development, in which tissues they are expressed remains uncharacterized, varying temporally and spatially. To address this, we used Hybridization Chain Reaction (HCR) to fluorescently visualize <em>rar</em> and <em>rxr</em> mRNA expression in tissue-specific transgenic zebrafish embryos. Here, we show the overall and tissue-specific expression of each receptor in the pharyngeal endoderm and Cranial Neural Crest Cells (CNCC), two cell types that have been shown to be sensitive to RA perturbations. Here we show that the expression of many of the <em>rar/rxr</em> genes overlap with the endoderm-specific <em>sox17:eGFP</em> and/or the CNCC-specific <em>sox10:eGFP</em> transgenic lines between 12 and 32 h post fertilization; time points that capture CNCC and endoderm migration and morphogenesis.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"140 ","pages":"Article 100822"},"PeriodicalIF":2.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11653530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774115","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":"Monoallelic loss of RB1 enhances osteogenic differentiation and delays DNA repair without inducing tumorigenicity","authors":"Ambily Vincent ,&nbsp;Subramanian Krishnakumar ,&nbsp;Sowmya Parameswaran","doi":"10.1016/j.diff.2024.100815","DOIUrl":"10.1016/j.diff.2024.100815","url":null,"abstract":"<div><div>The Retinoblastoma (<em>RB1)</em> gene plays a pivotal role in osteogenic differentiation. Our previous study, employing temporal gene expression analysis using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), revealed the deregulation of osteogenic differentiation in patient-derived heterozygous RB1 mutant orbital adipose-derived mesenchymal stem cells (OAMSCs). The study revealed increased Alizarin Red staining, suggesting heightened mineralization without a corresponding increase in osteogenic lineage-specific gene expression. In this study, we performed high-throughput RNA sequencing on <em>RB1</em>^<em>+/+</em> and <em>RB1</em>^{<em>+/−</em>} patient-derived OAMSCs differentiated towards the osteogenic lineage to investigate the pathways and molecular mechanisms. The pathway analysis revealed significant differences in cell proliferation, DNA repair, osteoblast differentiation, and cancer-related pathways in <em>RB1</em>^{<em>+/−</em>} OAMSC-derived osteocytes. These findings were subsequently validated through functional assays. The study revealed that osteogenic differentiation is increased in <em>RB1</em>^{<em>+/−</em>} cells, along with enhanced proliferation of the osteocytes. There were delayed but persistent DNA repair mechanisms in <em>RB1</em>^{<em>+/−</em>} osteocytes, which were sufficient to maintain genomic integrity, thereby preventing or delaying the onset of tumors. This contrasts with our earlier observation of increased mineralization without corresponding gene expression changes, emphasizing the importance of high-throughput analysis over preselected gene set analysis in comprehending functional assay results.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"140 ","pages":"Article 100815"},"PeriodicalIF":2.2,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142326633","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":"FGF12: biology and function","authors":"","doi":"10.1016/j.diff.2023.100740","DOIUrl":"10.1016/j.diff.2023.100740","url":null,"abstract":"<div><p><span>Fibroblast growth factor 12 (FGF12) belongs to the fibroblast growth factor homologous factors (FHF) subfamily, which is also known as the FGF11 subfamily. The human </span><em>FGF12</em><span><span><span> gene is located on chromosome 3<span><span> and consists of four introns and five coding exons. Their alternative splicing results in two FGF12 isoforms – the shorter ‘b’ isoform and the longer ’a’ isoform. Structurally, the core domain of FGF12, is highly homologous to that of the other FGF proteins, providing the classical </span>tertiary structure of β-trefoil. FGF12 is expressed in various tissues, most abundantly in excitable cells such as neurons and cardiomyocytes. For many years, FGF12 was thought to be exclusively an intracellular protein, but recent studies have shown that it can be secreted despite the absence of a canonical signal for secretion. The best-studied function of FGF12 relates to its interaction with sodium channels. In addition, FGF12 forms complexes with signaling proteins, regulates the </span></span>cytoskeletal system<span>, binds to the FGF receptors activating signaling cascades to prevent apoptosis and interacts with the </span></span>ribosome biogenesis complex. Importantly, FGF12 has been linked to nervous system disorders, cancers and cardiac diseases such as epileptic encephalopathy, pulmonary hypertension and cardiac arrhythmias, making it a potential target for gene therapy as well as a therapeutic agent.</span></p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"139 ","pages":"Article 100740"},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138479135","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}