Differentiation最新文献

{"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}

{"title":"FGF20","authors":"","doi":"10.1016/j.diff.2023.10.005","DOIUrl":"10.1016/j.diff.2023.10.005","url":null,"abstract":"<div><p>Fibroblast growth factor 20 (FGF20) is a neurotrophic factor and a member of the FGF9 subfamily. It was first identified in <em>Xenopus</em> embryos and was isolated shortly thereafter from the adult rat brain. Its receptors include FGFR4, FGFR3b, FGFR2b and the FGFRc splice forms. In adults it is highly expressed in the brain, while it is expressed in a variety of regions during embryonic development, including the inner ear, heart, hair placodes, mammary buds, dental epithelium and limbs. As a result of its wide-spread expression, <em>FGF20</em> mouse mutants exhibit a variety of phenotypes including congenital deafness, lack of hair, small kidneys and delayed mammary ductal outgrowth. <em>FGF20</em> is also associated with human diseases including Parkinson's Disease, cancer and hereditary deafness.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"139 ","pages":"Article 100737"},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301468123000762/pdfft?md5=8f8ddc5c2c340ebf4919b49753cc422f&pid=1-s2.0-S0301468123000762-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135509552","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":"Fibroblast growth factor 10","authors":"","doi":"10.1016/j.diff.2023.100741","DOIUrl":"10.1016/j.diff.2023.100741","url":null,"abstract":"<div><p><span><span><span>Fibroblast growth factor<span> 10 (FGF10) is a major morphoregulatory factor that plays essential signaling roles during vertebrate multiorgan development and homeostasis. FGF10 is predominantly expressed in mesenchymal cells and signals though </span></span>FGFR2b<span> in adjacent epithelia to regulate branching morphogenesis, stem cell fate, tissue differentiation and proliferation, in addition to autocrine roles. </span></span>Genetic<span> loss of function analyses have revealed critical requirements for FGF10 signaling during limb, lung, digestive system, ectodermal, nervous system, craniofacial and cardiac development. Heterozygous FGF10 mutations have been identified in human genetic syndromes associated with craniofacial anomalies, including lacrimal and salivary gland aplasia. Elevated </span></span><em>Fgf10</em> expression is associated with poor prognosis in a range of cancers. In addition to developmental and disease roles, FGF10 regulates homeostasis and repair of diverse adult tissues and has been identified as a target for regenerative medicine.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"139 ","pages":"Article 100741"},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138471170","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":"FGF5","authors":"","doi":"10.1016/j.diff.2023.10.004","DOIUrl":"10.1016/j.diff.2023.10.004","url":null,"abstract":"<div><p><span>FGF5 functions as a negative regulator of the hair cycle in mammals. It is expressed in the outer root sheath of hair follicles during the late anagen phase of the hair cycle. It functions as a signaling molecule, mediating the transition of the anagen growth phase to catagen regression phase of the hair cycle. Spontaneous and engineered </span><span><em>FGF5</em></span><span> mutations in mammalian animal models result in long hair phenotypes. In humans, inherited </span><em>FGF5</em> mutations result in trichomegaly (long eyelashes). Knockdown of <em>fgf5</em> in zebrafish embryos results in inner ear alterations. Alterations in <em>FGF5</em> expression are also associated with various human pathologies.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"139 ","pages":"Article 100736"},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92157224","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 21","authors":"","doi":"10.1016/j.diff.2024.100793","DOIUrl":"10.1016/j.diff.2024.100793","url":null,"abstract":"<div><p>Fibroblast growth factor 21<span><span> (FGF21) belongs to the FGF19 subfamily and acts systemically, playing a key role in inter-organ crosstalk. Ranging from metabolism, reproduction, and immunity, FGF21 is a pleiotropic hormone which contributes to various </span>physiological processes<span>. Although most of its production across species stems from hepatic tissues, expression of FGF21 in mice has also been identified in adipose tissue, thymus, heart, pancreas, and skeletal muscle. Elevated FGF21 levels are affiliated with various diseases and conditions, such as obesity, type 2 diabetes, preeclampsia, as well as cancer. Murine knockout models are viable and show modest weight gain, while overexpression and gain-of-function models display resistance to weight gain, altered bone volume, and enhanced immunity. In addition, FGF21-based therapies are at the forefront of biopharmaceutical strategies aimed at treating metabolic dysfunction-associated steatotic liver disease.</span></span></p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"139 ","pages":"Article 100793"},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592032","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":"FGF18","authors":"","doi":"10.1016/j.diff.2023.10.003","DOIUrl":"10.1016/j.diff.2023.10.003","url":null,"abstract":"<div><p><em>FGF18</em> was discovered in 1998. It is a pleiotropic growth factor that stimulates major signalling pathways involved in cell proliferation and growth, and is involved in the development and homeostasis of many tissues such as bone, lung, and central nervous system. The gene consists of five exons that code for a 207 amino acid glycosylated protein. <em>FGF18</em> is widely expressed in developing and adult chickens, mice, and humans, being seen in the mesenchyme, brain, skeleton, heart, and lungs. Knockout studies of <em>FGF18</em> in mice lead to perinatal death, characterised by distinct phenotypes such as cleft palate, smaller body size, curved long bones, deformed ribs, and reduced crania. As can be expected from a protein involved in so many functions <em>FGF18</em> is associated with various diseases such as idiopathic pulmonary fibrosis, congenital diaphragmatic hernia, and most notably various types of cancer such as breast, lung, and ovarian cancer.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"139 ","pages":"Article 100735"},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301468123000749/pdfft?md5=1acdf26f625714a9092eebc66a86c92d&pid=1-s2.0-S0301468123000749-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135510249","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":"Primer on fibroblast growth factor 7 (FGF 7)","authors":"Yangxi Zheng ,&nbsp;Wei-Hsin Liu ,&nbsp;Boxuan Yang ,&nbsp;Irit Milman Krentsis","doi":"10.1016/j.diff.2024.100801","DOIUrl":"10.1016/j.diff.2024.100801","url":null,"abstract":"<div><p>Fibroblast growth factor 7 (FGF7), also known as keratinocyte growth factor (KGF), is an important member of the FGF family that is mainly expressed by cells of mesenchymal origin while affecting specifically epithelial cells. Thus, FGF7 is widely expressed in diverse tissues, especially in urinary system, gastrointestinal tract (GI-tract), respiratory system, skin, and reproductive system. By interacting specifically with FGFR2-IIIb, FGF7 activates several downstream signal pathways, including Ras, PI3K-Akt, and PLCs. Previous studies of FGF7 mutants also have implicated its roles in various biological processes including development of essential organs and tissue homeostasis in adults. Moreover, more publications have reported that FGF7 and/or FGF7/FGFR2-IIIb-associated signaling pathway are involved in the progression of various heritable or acquired human diseases: heritable conditions like autosomal dominant polycystic kidney disease (ADPKD) and non-syndromic cleft lip and palate (NS CLP), where it promotes cyst formation and affects craniofacial development, respectively; acquired non-malignant diseases such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), mucositis, osteoarticular disorders, and metabolic diseases, where it influences inflammation, repair, and metabolic control; and tumorigenesis and malignant diseases, including benign prostatic hyperplasia (BPH), prostate cancer, gastric cancer, and ovarian cancer, where it enhances cell proliferation, invasion, and chemotherapy resistance. Targeting FGF7 pathways holds therapeutic potential for managing these conditions, underscoring the need for further research to explore its clinical applications. Having more insights into the function and underlying molecular mechanisms of FGF7 is warranted to facilitate the development of effective treatments in the future.</p><p>Here, we discuss FGF7 genomic structure, signal pathway, expression pattern during embryonic development and in adult organs and mutants along with phenotypes, as well as associated diseases.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"139 ","pages":"Article 100801"},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762360","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}