Differentiation最新文献

{"title":"Disruption of hedgehog signaling leads to hyoid bone dysplasia during embryogenesis","authors":"Yan Guo ,&nbsp;Xingyu Chen ,&nbsp;Yongzhen Lai ,&nbsp;Meng Lu ,&nbsp;Chengyong Wang ,&nbsp;Yun Shi ,&nbsp;Chengyan Ren ,&nbsp;Weihui Chen","doi":"10.1016/j.diff.2023.05.001","DOIUrl":"10.1016/j.diff.2023.05.001","url":null,"abstract":"<div><p>The development of the hyoid bone is a complex process that involves the coordination of multiple signaling pathways. Previous studies have demonstrated that disruption of the hedgehog pathway in mice results in a series of structural malformations. However, the specific role and critical period of the hedgehog pathway in the early development of the hyoid bone have not been thoroughly characterized. In this study, we treated pregnant ICR mice with the hedgehog pathway inhibitor vismodegib by oral gavage in order to establish a model of hyoid bone dysplasia. Our results indicate that administration of vismodegib at embryonic days 11.5 (E11.5) and E12.5 resulted in the development of hyoid bone dysplasia. We were able to define the critical periods for the induction of hyoid bone deformity through the use of a meticulous temporal resolution. Our findings suggest that the hedgehog pathway plays a crucial role in the early development of the hyoid bone. Additionally, our research has established a novel and easily established mouse model of synostosis in the hyoid bone using a commercially available pathway-selective inhibitor.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"131 ","pages":"Pages 82-88"},"PeriodicalIF":2.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9669823","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":"Fgf8 promotes survival of nephron progenitors by regulating BAX/BAK-mediated apoptosis","authors":"Matthew J. Anderson ,&nbsp;Salvia Misaghian ,&nbsp;Nirmala Sharma ,&nbsp;Alan O. Perantoni ,&nbsp;Mark Lewandoski","doi":"10.1016/j.diff.2022.12.001","DOIUrl":"10.1016/j.diff.2022.12.001","url":null,"abstract":"<div><p>Fibroblast growth factors (<em>Fgfs</em>) have long been implicated in processes critical to embryonic development, such as cell survival, migration, and differentiation. Several mouse models of organ development ascribe a prosurvival requirement specifically to FGF8. Here, we explore the potential role of prosurvival FGF8 signaling in kidney development. We have previously demonstrated that conditional deletion of <em>Fgf8</em> in the mesodermal progenitors that give rise to the kidney leads to renal aplasia in the mutant neonate. Deleterious consequences caused by loss of FGF8 begin to manifest by E14.5 when massive aberrant cell death occurs in the cortical nephrogenic zone in the rudimentary kidney as well as in the renal vesicles that give rise to the nephrons. To rescue cell death in the <em>Fgf8</em> mutant kidney, we inactivate the genes encoding the pro-apoptotic factors BAK and BAX. In a wild-type background, the loss of <em>Bak</em> and <em>Bax</em> abrogates normal cell death and has minimal effect on renal development. However, in <em>Fgf8</em> mutants, the combined loss of <em>Bak</em> and <em>Bax</em> rescues aberrant cell death in the kidneys and restores some measure of kidney development: 1) the nephron progenitor population is greatly increased; 2) some glomeruli form, which are rarely observed in <em>Fgf8</em> mutants; and 3) kidney size is rescued by about 50% at E18.5. The development of functional nephrons, however, is not rescued. Thus, FGF8 signaling is required for nephron progenitor survival by regulating BAK/BAX and for subsequent steps involving, as yet, undefined roles in kidney development.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"130 ","pages":"Pages 7-15"},"PeriodicalIF":2.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9486845","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":"Retinoic acid signaling in mouse retina endothelial cells is required for early angiogenic growth","authors":"Christina N. Como ,&nbsp;Cesar Cervantes ,&nbsp;Brad Pawlikowski ,&nbsp;Julie Siegenthaler","doi":"10.1016/j.diff.2022.12.002","DOIUrl":"10.1016/j.diff.2022.12.002","url":null,"abstract":"<div><p>The development of the retinal vasculature is essential to maintain health of the tissue, but the developmental mechanisms are not completely understood. The aim of this study was to investigate the cell-autonomous role of retinoic acid signaling in endothelial cells during retina vascular development. Using a temporal and cell-specific mouse model to disrupt retinoic acid signaling in endothelial cells in the postnatal retina (<em>Pdgfb</em>^{<em>icre/+</em>} <em>dnRAR403</em>^{<em>fl/fl</em>} mutants), we discovered that angiogenesis in the retina is significantly decreased with a reduction in retina vascularization, endothelial tip cell number and filipodia, and endothelial ‘crowding’ of stalk cells. Interestingly, by P15, the vasculature can overcome the early angiogenic defect and fully vascularized the retina. At P60, the vasculature is intact with no evidence of retina cell death or altered blood retinal barrier integrity. Further, we identified that the angiogenic defect seen in mutants at P6 correlates with decreased <em>Vegfr3</em> expression in endothelial cells. Collectively, our work identified a previously unappreciated function for endothelial retinoic acid signaling in early retinal angiogenesis.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"130 ","pages":"Pages 16-27"},"PeriodicalIF":2.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10006372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9486849","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":"T, NK, then macrophages: Recent advances and challenges in adaptive immunotherapy from human pluripotent stem cells","authors":"Su Hang ,&nbsp;Nan Wang ,&nbsp;Ryohichi Sugimura","doi":"10.1016/j.diff.2023.01.001","DOIUrl":"10.1016/j.diff.2023.01.001","url":null,"abstract":"<div><p>Adaptive cellular immunotherapy, especially chimeric antigen receptor-T (CAR-T) cell therapy, has advanced the treatment of hematological malignancy. However, major limitations still remain in the source of cells comes from the patients themselves. The use of human pluripotent stem cells to differentiate into immune cells, such as T cells, NK cells, and macrophages, then arm with chimeric antigen receptor (CAR) to enhance tumor killing has gained major attention. It is expected to solve the low number of immune cells recovery from patients, long waiting periods, and ethical issues(reprogramming somatic cells to produce induced pluripotent stem cells (iPS cells) avoids the ethical issues unique to embryonic stem cells (<span>Lo and Parham, 2009</span>). However, there are still major challenges to be further solved. This review summarizes the progress, challenges, and future direction in human pluripotent stem cell-based immunotherapy.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"130 ","pages":"Pages 51-57"},"PeriodicalIF":2.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9487938","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":"Facile methods for reusing laboratory plastic in developmental biology experiments","authors":"Maggie Clancy,&nbsp;Isabel S. Wade,&nbsp;John J. Young","doi":"10.1016/j.diff.2022.11.001","DOIUrl":"10.1016/j.diff.2022.11.001","url":null,"abstract":"<div><p>Plastic pollution negatively affects ecosystems and human health globally, with single-use plastic representing the majority of marine litter in some areas. Life science laboratories prefer pristine conditions for experimental reliability and therefore make use of factory standardized single-use plastic products. This contributes to overall plastic waste in the United States and globally. Here, we investigate the potential of reusing plastic culture dishes and subsequently propose methods to mitigate single-use plastic waste in developmental biology research laboratories. We tested the efficacy of bleach and ethyl alcohol in sterilizing used dishes. We then tested the feasibility of washing and reusing plastic to culture <em>Xenopus laevis</em> embryos subjected to various manipulations. Cleaning and reusing laboratory plastic did not affect the development or survival of <em>X. laevis</em>, indicating that these cleaning methods do not adversely affect experimental outcome and can be used to sterilize plastic before reuse or recycling. Lastly, we performed a survey of various life science laboratories to estimate both waste reduction and savings associated with recycling single-use plastics. Standardization of these procedures would allow research laboratories to benefit economically while practicing environmentally conscious consumption.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"130 ","pages":"Pages 1-6"},"PeriodicalIF":2.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9111723","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":"Tuberin levels during cellular differentiation in brain development","authors":"Elizabeth Fidalgo da Silva,&nbsp;Bashaer Abu Khatir ,&nbsp;Christopher Drouillard ,&nbsp;Isabelle Hinch ,&nbsp;Gordon Omar Davis,&nbsp;Mariam Sameem,&nbsp;Rutu Patel,&nbsp;Jackie Fong,&nbsp;Dorota Lubanska,&nbsp;Lisa A. Porter","doi":"10.1016/j.diff.2022.12.004","DOIUrl":"10.1016/j.diff.2022.12.004","url":null,"abstract":"<div><p>Tuberin is a member of a large protein complex, Tuberous Sclerosis Complex (TSC), and acts as a sensor for nutrient status regulating protein synthesis and cell cycle progression. Mutations in the Tuberin gene, <em>TSC2</em>, permits the formation of tumors that can lead to developmental defects in many organ systems, including the central nervous system. Tuberin is expressed in the brain throughout development and levels of Tuberin have been found to decrease during neuronal differentiation in cell lines <em>in vitro.</em> Our current work investigates the levels of Tuberin at two stages of embryonic development <em>in vivo</em>, and we study the mRNA and protein levels during a time course using immortalized cell lines <em>in vitro</em>. Our results show that total Tuberin levels are tightly regulated through developmental stages in the embryonic brain. At a cell biology level, we show that Tuberin levels are higher when cells are cultured as neurospheres, and knockdown of Tuberin results in a reduction in the number of neurospheres. This functional data supports the hypothesis that Tuberin is an important regulator of stemness and the reduction of Tuberin levels might support functional differentiation in the central nervous system. Understanding how Tuberin expression is regulated throughout neural development is essential to fully comprehend the role of this protein in several developmental and neural pathologies.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"130 ","pages":"Pages 43-50"},"PeriodicalIF":2.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9471048","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":"The International Society of Differentiation: Past, present, and future","authors":"Richard R. Behringer ,&nbsp;Robert G. McKinnell ,&nbsp;Dimitri Viza ,&nbsp;Alan O. Perantoni ,&nbsp;Elizabeth J. Robertson ,&nbsp;Sally L. Dunwoodie ,&nbsp;Mark Lewandoski","doi":"10.1016/j.diff.2022.12.003","DOIUrl":"10.1016/j.diff.2022.12.003","url":null,"abstract":"<div><p>The International Society of Differentiation was born from the First International Conference on Cell Differentiation conceived by D.V. and held in Nice, France in 1971. The conference also resulted in the creation of the journal of the Society named <em>Differentiation</em>. The Society advocates for the field of differentiation through the journal <em>Differentiation</em>, organizing and supporting international scientific conferences, honoring scientific achievements, and supporting trainees.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"130 ","pages":"Pages 28-31"},"PeriodicalIF":2.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9486857","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":"Zebrafish anterior segment mesenchyme progenitors are defined by function of tfap2a but not sox10","authors":"Oliver Vöcking ,&nbsp;K. Van Der Meulen,&nbsp;M.K. Patel,&nbsp;J.K. Famulski","doi":"10.1016/j.diff.2022.11.002","DOIUrl":"10.1016/j.diff.2022.11.002","url":null,"abstract":"<div><p>The anterior segment is a critical component of the visual system. Developing independent of the retina, the AS relies partially on cranial neural crest cells (cNCC) as its earliest progenitors. The cNCCs are thought to first adopt a periocular mesenchyme (POM) fate and subsequently target to the AS upon formation of the rudimentary retina. AS targeted POM is termed anterior segment mesenchyme (ASM). However, it remains unknown when and how the switch from cNCC to POM or POM to ASM takes place. As such, we sought to visualize the timing of these transitions and identify the regulators of this process using the zebrafish embryo model. Using two color fluorescence in situ hybridization, we tracked cNCC and ASM target gene expression from 12 to 24hpf. In doing so, we identified a <em>tfap2a</em> and <em>foxC1a</em> co-expression at 16hpf, identifying the earliest ASM to arrive at the AS. Interestingly, expression of two other key regulators of NCC, <em>foxD3</em> and <em>sox10</em> was not associated with early ASM. Functional analysis of tfap2a, foxD3 and sox10 revealed that tfap2a and foxD3 are both critical regulators of ASM specification and AS formation while sox10 was dispensable for either specification or development of the AS. Using genetic knockout lines, we show that in the absence of tfap2a or foxD3 function ASM cells are not specified, and subsequently the AS is malformed. Conversely, sox10 genetic mutants or CRISPR Cas9 injected embryos displayed no defects in ASM specification, migration or the AS. Lastly, using transcriptomic analysis, we show that GFP + cNCCs derived from Tg [<em>foxD3</em>:GFP] and Tg [<em>foxC1b</em>:GFP] share expression profiles consistent with ASM development whereas cNCCs isolated from Tg [<em>sox10</em>:GFP] exhibit expression profiles associated with vasculogenesis, muscle function and pigmentation. Taken together, we propose that the earliest stage of anterior segment mesenchyme (ASM) specification in zebrafish is approximately 16hpf and involves tfap2a/foxC1a positive cNCCs.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"130 ","pages":"Pages 32-42"},"PeriodicalIF":2.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10006344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9486861","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":"Early development of the human embryonic testis","authors":"Marta Himelreich Perić ,&nbsp;Marta Takahashi ,&nbsp;Davor Ježek ,&nbsp;Gerald R. Cunha","doi":"10.1016/j.diff.2022.07.001","DOIUrl":"10.1016/j.diff.2022.07.001","url":null,"abstract":"<div><p>Human gonadal development culminating in testicular differentiation is described through analysis of histologic sections derived from 33-day to 20-week human embryos/fetuses, focusing on early development (4–8 weeks of gestation). Our study updates the comprehensive studies of Felix (1912), van Wagenen and Simpson (1965), and Juric-Lekic et al. (2013), which were published in books and thus are unsearchable via PubMed. Human gonads develop from the germinal ridge, a thickening of coelomic epithelium on the medial side of the urogenital ridge. The bilateral urogenital ridges contain elements of the mesonephric kidney, namely the mesonephric duct, mesonephric tubules, and mesonephric glomeruli. The germinal ridge, into which primordial germ cells migrate, is initially recognized as a thickening of coelomic epithelium on the urogenital ridge late in the 4th week of gestation. Subsequently, in the 5th week of gestation, a dense mesenchyme develops sub-adjacent to the epithelium of the germinal ridge, and together these elements bulge into the coelomic cavity forming bilateral longitudinal ridges attached to the urogenital ridges. During development, primordial cells migrate into the germinal ridge and subsequently into testicular cords that form within the featureless dense mesenchyme of the germinal ridge at 6–8 weeks of gestation. The initial low density of testicular cords seen at 8 weeks remodels into a dense array of testicular cords surrounded by α-actin-positive myoid cells during the second trimester. Human testicular development shares many features with that of mice being derived from 4 elements: coelomic epithelium, sub-adjacent mesenchyme, primordial germ cells, and the mesonephros.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"129 ","pages":"Pages 4-16"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9173147","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":"Role of mesonephric contribution to mouse testicular development revisited","authors":"Gerald R. Cunha ,&nbsp;Mei Cao ,&nbsp;Sena Aksel ,&nbsp;Amber Derpinghaus ,&nbsp;Laurence S. Baskin","doi":"10.1016/j.diff.2021.11.002","DOIUrl":"10.1016/j.diff.2021.11.002","url":null,"abstract":"<div><p>The role of the mesonephros in testicular development was re-evaluated by growing embryonic day 11.5 (E11.5) mouse testes devoid of mesonephros for 8–21 days in vivo under the renal capsule of castrated male athymic nude mice. This method provides improved growth conditions relative to previous studies based upon short-term (4–7 days) organ culture. Meticulous controls involved wholemount examination of dissected E11.5 mouse testes as well as serial sections of dissected E11.5 mouse testes which were indeed shown to be devoid of mesonephros. As expected, grafts of E11.5 mouse testes with mesonephros attached formed seminiferous tubules and also contained mesonephric derivatives. Grafts of E11.5 mouse testes without associated mesonephros also formed seminiferous tubules and never contained mesonephric derivatives. The consistent absence of mesonephric derivatives in grafts of E11.5 mouse testes grafted alone is further proof of the complete removal of the mesonephros from the E11.5 mouse testes. The testicular tissues that developed in grafts of E11.5 mouse testes alone contained canalized seminiferous tubules composed of Sox9-positive Sertoli cells as well as GENA-positive germ cells. The seminiferous tubules were surrounded by α-actin-positive myoid cells, and the interstitial space contained 3βHSD-1-positive Leydig cells. Grafts of E11.5 GFP mouse testes into wild-type hosts developed GFP-positive vasculature indicating that E11.5 mouse testes contain vascular precursors. These results indicate that the E11.5 mouse testis contains precursor cells for Sertoli cells, Leydig cells, myoid cells and vasculature whose development and differentiation are independent of cells migrating from the E11.5 mesonephros.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"129 ","pages":"Pages 109-119"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10570011","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}