Differentiation最新文献

{"title":"A model to study human ovotesticular syndrome","authors":"Laurence Baskin,&nbsp;Mei Cao,&nbsp;Amber Derpinghaus,&nbsp;Sena Aksel,&nbsp;Maya Overland,&nbsp;Yi Li,&nbsp;Gerald Cunha","doi":"10.1016/j.diff.2021.12.003","DOIUrl":"10.1016/j.diff.2021.12.003","url":null,"abstract":"<div><p>Ovotesticular syndrome is a rare disorder of sex development characterized by the presence of testicular and ovarian tissue. The histologic characteristics of human testicular tissue are well defined by the presence of seminiferous cords or tubules containing TSPY-positive germ cells and Sox9-positive Sertoli cells surrounded by interstitial tissue containing cytochrome P450-positive Leydig cells and smooth muscle α-actin-positive peritubular myoid cells. The histological characteristics of the ovary can be defined by germ cell nests and the development of follicles. In contrast to the testis, the ovary has a paucity of defined specific protein markers, with the granulosa cell marker FOXL2 being the most widely used. In practice, defining the ovarian component of the ovotestis can be quite difficult.</p><p>We developed a model of human ovotesticular syndrome by combining fetal human testis and ovary in a xenograft model. Ovotesticular xenografts were grown under the renal capsules of gonadectomized athymic nude mice for 6–32 weeks along with age matched control grafts of fetal testis and ovary. Forty ovotesticular xenografts and their controls were analyzed by histology, immunohistochemistry, and fluorescent <em>in situ</em> hybridization to determine the protein expression and karyotype of the cells within the grafts.</p><p>The ovotesticular xenografts exhibited recognizable testicular and ovarian tissue based on testis-specific and ovary-specific markers defined above. The xenografts simulated a bipolar ovotestis in which the testicular and ovarian elements retain their separate histological characteristics and are separated by a well-defined border. This contrasts with the compartmentalized ovotestis previously described in the literature where the testicular tissue is surrounded by ovarian tissue or a mixed histology where testicular and ovarian tissues are interspersed throughout the gonad.</p><p>In conclusion, we have characterized a human model of ovotestis which will allow a deeper understanding of ovotestis development in humans and facilitate a more accurate diagnosis of the ovotesticular syndrome.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"129 ","pages":"Pages 60-78"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10568032","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":"Development of the human fetal testis: Morphology and expression of cellular differentiation markers","authors":"Yi Li ,&nbsp;Maya Overland ,&nbsp;Amber Derpinghaus ,&nbsp;Sena Aksel ,&nbsp;Mei Cao ,&nbsp;Nicholas Ladwig ,&nbsp;Gerald R. Cunha ,&nbsp;Laurence S. Baskin","doi":"10.1016/j.diff.2022.03.002","DOIUrl":"10.1016/j.diff.2022.03.002","url":null,"abstract":"<div><p>A comprehensive immunohistochemical ontogeny of the developing human fetal testis has remained incomplete in the literature to date. We collected human fetal testes from 8 to 21 weeks of fetal age, as well as postnatal human testes at minipuberty, pre-pubertal, and pubertal stages. Immunohistochemistry was performed with a comprehensive panel of antigens targeting gonadocytes, Sertoli cells, fetal Leydig cells, peritubular myoid cells, and other hormonal and developmental targets.</p><p>Testicular cords, precursor structures to seminiferous tubules, developed from 8 to 14 weeks of fetal age, separating the testis into the interstitial and intracordal compartments. Fetal gonadocytes were localized within the testicular cords and evaluated for Testis-Specific Protein Y, Octamer-binding transcription factor 4, Sal-like protein 4, and placental alkaline phosphatase expression. Fetal Sertoli cells were also localized in the testicular cords and evaluated for SRY-box Transcription Factor 9, inhibin, and anti-Mullerian hormone expression. Fetal Leydig cells were present in the interstitium and stained for cytochrome p450c17 and calretinin, while interstitial peritubular myoid cells were examined using smooth muscle α-actin staining. Androgen receptor expression was localized close to the testicular medulla at 8 weeks and then around the testicular cords in the interstitium as they matured in structure.</p><p>Postnatal staining showed that Testis-Specific Protein Y remained positive of male gonadocytes throughout adulthood. Anti-Mullerian hormone, SRY-box Transcription Factor 9, and Steroidogenic factor 1 are expressed by the postnatal Sertoli cells at all ages examined. Leydig cell markers cytochrome p450c17 and calretinin are expressed during mini-puberty and puberty, but not expressed during the pre-pubertal period. Smooth muscle α-actin and androgen receptor were not expressed during mini-puberty or pre-puberty, but again expressed during the pubertal period.</p><p>The ontogenic map of the human fetal and postnatal testicular structure and expression patterns described here will serve as a reference for future investigations into normal and abnormal testicular development.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"129 ","pages":"Pages 17-36"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10573917","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":"Hox proteins as regulators of extracellular matrix interactions during neural crest migration","authors":"Aubrey G.A. Howard IV ,&nbsp;Rosa A. Uribe","doi":"10.1016/j.diff.2022.09.003","DOIUrl":"10.1016/j.diff.2022.09.003","url":null,"abstract":"<div><p>Emerging during embryogenesis, the neural crest are a migratory, transient population of multipotent stem cell that differentiates into various cell types in vertebrates. Neural crest cells arise along the anterior-posterior extent of the neural tube, delaminate and migrate along routes to their final destinations. The factors that orchestrate how neural crest cells undergo delamination and their subsequent sustained migration is not fully understood. This review provides a primer about neural crest epithelial-to-mesenchymal transition (EMT), with a special emphasis on the role of the Extracellular matrix (ECM), cellular effector proteins of EMT, and subsequent migration. We also summarize published findings that link the expression of Hox transcription factors to EMT and ECM modification, thereby implicating Hox factors in regulation of EMT and ECM remodeling during neural crest cell ontogenesis.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"128 ","pages":"Pages 26-32"},"PeriodicalIF":2.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301468122000731/pdfft?md5=d2fe301f07f65b349872ff55cda6243e&pid=1-s2.0-S0301468122000731-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9088165","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 neurogenic properties of iPSC-derived neurosphere formation in Japanese macaque monkeys","authors":"Risako Nakai ,&nbsp;Yusuke Hamazaki ,&nbsp;Haruka Ito ,&nbsp;Masanori Imamura","doi":"10.1016/j.diff.2022.10.002","DOIUrl":"10.1016/j.diff.2022.10.002","url":null,"abstract":"<div><p><span>Non-human primates are important models for investigations of neural development and evolution, and the use of Japanese macaque<span> monkeys has especially contributed to the advancement of neuroscience studies. However, these studies are restricted by the number of animals able to be evaluated and the invasiveness of the methodologies. Induced pluripotent stem cells (iPSCs) can provide an alternative strategy for investigating neural development </span></span><em>in vitro</em>. We have established direct neurosphere (dNS) formation cultures of primate iPSCs as an <em>in vitro</em><span> model of early neurodevelopment in primate species. Here, we used dNS formation and neuronal differentiation cultures established from Japanese macaque iPSCs (jm-iPSCs) to investigate the usefulness of these cells as an </span><em>in vitro</em> model of early neural development. Time-course analyses of developmental potency and gene expression kinetics were performed during dNS formation culture of jm-iPSCs. During a 1-week culture, jm-iPSC-derived dNSs became neurogenic by day 3 and underwent stepwise expression changes of key developmental regulators along early neural development in a similar manner to chimpanzee dNS formation previously reported. Meanwhile, a subset of genes, including <span><em>CYP26A1</em></span> and <em>NPTX1</em>, showed differential expression propensity in Japanese macaque, chimpanzee, and human iPSC-derived dNSs. Spontaneous upregulation of NOTCH signaling-associated genes <em>HES5</em> and <em>DLL1</em> was also observed in neuronal differentiation cultures of Japanese macaque but not chimpanzee dNSs, possibly reflecting the earlier neurogenic competence in Japanese macaques. The use of jm-iPSCs provides an alternative approach to neurological studies of primate development. Furthermore, jm-iPSCs can be used to investigate species differences in early neural development that are key to primate evolution.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"128 ","pages":"Pages 33-42"},"PeriodicalIF":2.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10735890","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":"Myhre syndrome is caused by dominant-negative dysregulation of SMAD4 and other co-factors","authors":"Dimuthu Alankarage ,&nbsp;Annabelle Enriquez ,&nbsp;Robert D. Steiner ,&nbsp;Cathy Raggio ,&nbsp;Megan Higgins ,&nbsp;Di Milnes ,&nbsp;David T. Humphreys ,&nbsp;Emma L. Duncan ,&nbsp;Duncan B. Sparrow ,&nbsp;Philip F. Giampietro ,&nbsp;Gavin Chapman ,&nbsp;Sally L. Dunwoodie","doi":"10.1016/j.diff.2022.09.002","DOIUrl":"10.1016/j.diff.2022.09.002","url":null,"abstract":"<div><p><span><span>Myhre syndrome is a connective tissue disorder characterized by congenital cardiovascular, craniofacial, respiratory, skeletal, and cutaneous anomalies as well as intellectual disability and progressive fibrosis. It is caused by </span>germline variants in the transcriptional co-regulator </span><span><em>SMAD4</em></span><span> that localize at two positions within the SMAD4 protein, I500 and R496, with I500 V/T/M variants more commonly identified in individuals with Myhre syndrome. Here we assess the functional impact of SMAD4-I500V variant, identified in two previously unpublished individuals with Myhre syndrome, and provide novel insights into the molecular mechanism of SMAD4-I500V dysfunction. We show that SMAD4-I500V can dimerize, but its transcriptional activity is severely compromised. Our data show that SMAD4-I500V acts dominant-negatively on SMAD4 and on receptor-regulated SMADs, affecting transcription of target genes. Furthermore, SMAD4-I500V impacts the transcription and function of crucial developmental transcription regulator, NKX2-5. Overall, our data reveal a dominant-negative model of disease for SMAD4-I500V where the function of SMAD4 encoded on the remaining allele, and of co-factors, are perturbed by the continued heterodimerization of the variant, leading to dysregulation of TGF and BMP signaling<span>. Our findings not only provide novel insights into the mechanism of Myhre syndrome pathogenesis but also extend the current knowledge of how pathogenic variants in SMAD proteins cause disease.</span></span></p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"128 ","pages":"Pages 1-12"},"PeriodicalIF":2.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10039907","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":"Macrophage polarization in THP-1 cell line and primary monocytes: A systematic review","authors":"Zahidah Nasuha Mohd Yasin ,&nbsp;Fatin Najiah Mohd Idrus ,&nbsp;Chee Hock Hoe ,&nbsp;Get Bee Yvonne-Tee","doi":"10.1016/j.diff.2022.10.001","DOIUrl":"10.1016/j.diff.2022.10.001","url":null,"abstract":"<div><p>Macrophages derived from human monocytic leukemia THP-1 cell line are often used as the alternative of human primary macrophage. However, the polarization method of THP-1 to macrophages varies between different laboratories, which may unknowingly affect the relevance of research output across research groups. In this regard, a systematic search was developed in Pubmed, BioOne, Scopus, and Science Direct to identify articles focusing on THP-1 polarization into M1 and M2 macrophages. All selected articles were read and discussed by two independent reviewers. The selection process was based on selected keywords on the title, abstract and full-text level. A total of 85 articles were selected and categorized based on the field of studies, method of THP-1 differentiation, and markers or genes expressed upon differentiation. THP-1 derived macrophages were mainly used together with primary monocyte-derived macrophages in cellular inflammation studies, while it was commonly employed alone in cancer research. THP-1 derived macrophages are also of paramount importance in biomaterials studies to prevent unfavorable immune responses in-vivo. We explored various methods of THP-1 differentiation and suggested several common genes encountered to characterize M1 and M2 macrophages differentiated from THP-1. The systematic review highlights the relevance of using THP-1 derived macrophage as a useful alternative to primary macrophage. Although it is not possible to derive a standard method of THP-1 polarization into M1 and M2 macrophages from this review, it may lead researchers to obtain reproducible polarization protocol based on commonly used stimulants and markers of differentiation.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"128 ","pages":"Pages 67-82"},"PeriodicalIF":2.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10718287","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":"Regulation of Wnt signaling by non-coding RNAs during osteoblast differentiation","authors":"I. Saranya,&nbsp;R.L. Akshaya,&nbsp;N. Selvamurugan","doi":"10.1016/j.diff.2022.10.003","DOIUrl":"10.1016/j.diff.2022.10.003","url":null,"abstract":"<div><p><span><span>Bone is a rigid, mineralized connective tissue that constitutes part of the skeleton in most vertebrate animals. Bone remodeling is a complex process that involves the coordination of ossification and </span>bone resorption activities by osteoblasts and </span>osteoclasts<span>, respectively, resulting in maintaining bone mass. This process involves several growth factors/cytokines and hormones regulating the various signaling pathways<span>. Wnt is one of the major molecular signaling pathways that positively regulate the osteogenic differentiation of mesenchymal stem cells. Dysregulation in the Wnt signaling<span> leads to serious bone-related disorders like osteoporosis and osteosclerosis. Recently, several studies reported the critical role of non-coding RNAs (ncRNAs), including microRNAs<span><span><span>, long ncRNAs, and </span>circular RNAs, in the regulation of bone </span>homeostasis via modulating the Wnt signaling cascade. This review summarizes the importance of such ncRNAs in mediating the Wnt cascade and its effect on osteoblast differentiation. Understanding the regulatory role of these ncRNAs would serve as a novel therapeutic strategy for treating bone-related disorders.</span></span></span></span></p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"128 ","pages":"Pages 57-66"},"PeriodicalIF":2.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10718288","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":"Steroidogenic factor 1 (NR5A1) induces multiple transcriptional changes during differentiation of human gonadal-like cells","authors":"Kirsi Sepponen ,&nbsp;Karolina Lundin ,&nbsp;Dawit A. Yohannes ,&nbsp;Sanna Vuoristo ,&nbsp;Diego Balboa ,&nbsp;Matti Poutanen ,&nbsp;Claes Ohlsson ,&nbsp;Steinar Hustad ,&nbsp;Ersilia Bifulco ,&nbsp;Pauliina Paloviita ,&nbsp;Timo Otonkoski ,&nbsp;Olli Ritvos ,&nbsp;Kirsi Sainio ,&nbsp;Juha S. Tapanainen ,&nbsp;Timo Tuuri","doi":"10.1016/j.diff.2022.08.001","DOIUrl":"10.1016/j.diff.2022.08.001","url":null,"abstract":"<div><p>Nuclear receptor subfamily 5 group A member 1 (<em>NR5A1</em>) encodes steroidogenic factor 1 (SF1), a key regulatory factor that determines gonadal development and coordinates endocrine functions. Here, we have established a stem cell-based model of human gonadal development and applied it to evaluate the effects of <em>NR5A1</em> during the transition from bipotential gonad to testicular cells. We combined directed differentiation of human induced pluripotent stem cells (46,XY) with activation of endogenous <em>NR5A1</em> expression by conditionally-inducible CRISPR activation. The resulting male gonadal-like cells expressed several Sertoli cell transcripts, secreted anti-Müllerian hormone and responded to follicle-stimulating hormone by producing sex steroid intermediates. These characteristics were not induced without <em>NR5A1</em> activation. A total of 2691 differentially expressed genetic elements, including both coding and non-coding RNAs, were detected immediately following activation of <em>NR5A1</em> expression. Of those, we identified novel gonad-related putative <em>NR5A1</em> targets, such as SCARA5, which we validated also by immunocytochemistry. In addition, <em>NR5A1</em> activation was associated with dynamic expression of multiple gonad- and infertility-related differentially expressed genes. In conclusion, by combining targeted differentiation and endogenous activation of <em>NR5A1</em> we have for the first time, been able to examine in detail the effects of <em>NR5A1</em> in early human gonadal cells. The model and results obtained provide a useful resource for future investigations exploring the causative reasons for gonadal dysgenesis and infertility in humans.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"128 ","pages":"Pages 83-100"},"PeriodicalIF":2.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301468122000627/pdfft?md5=0da28e3431e42b334933817e1c25a649&pid=1-s2.0-S0301468122000627-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10372188","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":"Comparative role of SOX10 gene in the gliogenesis of central, peripheral, and enteric nervous systems","authors":"Chacchu Bhattarai ,&nbsp;Phanindra P. Poudel ,&nbsp;Arnab Ghosh ,&nbsp;Sneha G. Kalthur","doi":"10.1016/j.diff.2022.09.001","DOIUrl":"10.1016/j.diff.2022.09.001","url":null,"abstract":"<div><p><span><em>SOX10</em></span><span><span> gene and SOX10 protein are responsible for the gliogenesis of </span>neuroglia<span> from the neural crest cells. Expression of </span></span><em>SOX10</em><span> gene encodes SOX10 protein which binds with DNA<span> at its minor groove via its HMG domain upon activation. SOX10 protein undergoes bending and changes its conformation after binding with DNA. Via its transactivation domain and HMG domain, it further activates several other transcription factors, these cause gliogenesis of the neural crest cells into neuroglia. In literature, it is stated that the </span></span><em>SOX10</em><span> gene helps in the formation of schwann cells<span>, oligodendrocytes, and enteric ganglia from neural crest cells. Altered expression of the </span></span><em>SOX10</em> gene results in agliogenesis, dysmyelination, and demyelination in the nervous system as well as intestinal aganglionosis. This review highlighted that there is a role of the <em>SOX10</em> gene and SOX10 protein in enteric gliogenesis from the neural crest cells.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"128 ","pages":"Pages 13-25"},"PeriodicalIF":2.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10372228","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":"Interferon-beta induces major histocompatibility complex of class I (MHC-I) expression and a proinflammatory phenotype in cultivated human astrocytes","authors":"Raffaela Silvestre Ignarro ,&nbsp;André Luis Bombeiro ,&nbsp;Gabriela Bortolança Chiarotto ,&nbsp;Luciana Politti Cartarozzi ,&nbsp;Lilian de Oliveira Coser ,&nbsp;Enrico Ghizoni ,&nbsp;Helder Tedeschi ,&nbsp;Fernando Cendes ,&nbsp;Iscia Lopes-Cendes ,&nbsp;Fabio Rogerio ,&nbsp;Alexandre Leite Rodrigues de Oliveira","doi":"10.1016/j.diff.2022.10.004","DOIUrl":"10.1016/j.diff.2022.10.004","url":null,"abstract":"<div><p><span><span>Major histocompatibility complex class I (MHC-I) has been implicated in several types of neuroplasticity phenomena. Interferon beta-1b (IFN-β) increases MHC-I expression by motoneurons after sciatic nerve crush in mice, improving axonal growth and functional recovery. Additionally, IFN-β induces glial hypertrophy associated with upregulation of </span>glial fibrillary acidic protein (GFAP) and MHC-I in murine astrocytes </span><em>in vitro</em><span><span><span>. As knowledge about MHC-I and its role in synaptic plasticity in human astrocytes (HAs) is scarce, we investigated these aspects in mature HAs obtained from the neocortex of patients undergoing surgery due to hippocampal sclerosis. Cells were exposed to media in the absence (0 IU/ml) or presence of IFN-β for 5 days (500 IU/ml). Beta-2 microglobulin (β2m), a component of the MHC-I, GFAP and vimentin proteins, was quantified by flow cytometry (FC) and increased by 100%, 60% and 46%, respectively, after IFN-β exposure. We also performed qRT–PCR gene expression analyses for </span>β2m, GFAP, vimentin, and pro- and anti-inflammatory cytokines. Our data showed that IFN-β-treated astrocytes displayed β2m and GFAP gene upregulation. Additionally, they presented a proinflammatory profile with increase in the IL-6 and IL-1β genes and a tendency to upregulate TNF-α. Moreover, we evaluated the effect of HAs conditioned medium (CM) on the formation/maintenance of neurites/synapses by the PC12 lineage. </span>Synaptophysin<span> protein expression was quantified by FC. The CM of IFN-β-activated astrocytes was not harmful to PC12 neurites, and there was no change in synaptophysin protein expression. Therefore, IFN-β activated HAs by increasing GFAP, vimentin and MHC-I protein expression. Like MHC-I modulation and astrocyte activation may be protective after peripheral nerve damage and in some neurodegenerative conditions, this study opens perspectives on the pathophysiological roles of astroglial MHC-I in the human CNS.</span></span></p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"128 ","pages":"Pages 43-56"},"PeriodicalIF":2.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10366711","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}