Differentiation最新文献

{"title":"The primary cilia: Orchestrating cranial neural crest cell development.","authors":"Hiroyuki Yamaguchi, Matthew D Meyer, William B Barrell, Maryam Faisal, Rebecca Berdeaux, Karen J Liu, Yoshihiro Komatsu","doi":"10.1016/j.diff.2024.100818","DOIUrl":"https://doi.org/10.1016/j.diff.2024.100818","url":null,"abstract":"<p><p>Primary cilia (hereafter \"cilia\") are microtubule-based antenna-like organelles projecting from the surface of vertebrate cells. Cilia can serve as cellular antennae controlling cell growth and differentiation. Absent or dysfunctional cilia frequently lead to craniofacial anomalies known as craniofacial ciliopathies. However, the detailed pathological mechanisms of craniofacial ciliopathies remain unclear. This perspective discusses our current understanding of the role of cilia in cranial neural crest cells. We also describe potential mechanisms of ciliogenesis in cranial neural crest cells, which may contribute to unraveling the complex pathogenesis of craniofacial ciliopathies.</p>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583649","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, Roel Nusse, Peng V Wu","doi":"10.1016/j.diff.2024.100816","DOIUrl":"https://doi.org/10.1016/j.diff.2024.100816","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-10-24","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":"","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":null,"pages":null},"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":"Fibroblast Growth Factor (FGF) 13.","authors":"Lucia J Rivas, Rosa A Uribe","doi":"10.1016/j.diff.2024.100814","DOIUrl":"https://doi.org/10.1016/j.diff.2024.100814","url":null,"abstract":"<p><p>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. Fgf13 mutant mouse lines display various neurological pathologies. Through sequence mapping, FGF13 is considered a candidate causative gene that is mutated in multiple human X-linked neurological diseases.</p>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-25","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":"Fgf17: A regulator of the mid/hind brain boundary in mammals.","authors":"Zane Oberholzer, Chiron Loubser, Natalya V Nikitina","doi":"10.1016/j.diff.2024.100813","DOIUrl":"https://doi.org/10.1016/j.diff.2024.100813","url":null,"abstract":"<p><p>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 Fgf8/FgfD subfamily member, Fgf17, 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. Fgf17 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 Fgf17^-/- 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, FGF17 mutations are implicated in several diseases, including Congenital Hypogonadotropic Hypogonadism and Kallmann Syndrome. FGF17 mutations contribute to CHH/KS in 1.1% of affected individuals, often presenting in conjunction with mutations in other FGF pathway genes like FGFR1 and FLRT3. FGF17 mutations were also identified in patients diagnosed with Dandy-Walker malformation and Pituitary Stalk Interruption Syndrome, however, it remains unclear how FGF17 is implicated in these diseases. Altered FGF17 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.</p>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-16","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":"","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":null,"pages":null},"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":"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":null,"pages":null},"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":"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":null,"pages":null},"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":null,"pages":null},"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":"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":null,"pages":null},"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}