Browsing by Subject "Differentiation"
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- PublicationOpen AccessCells from the inner mass of blastocyst as a source of neural derivates for differentiation studies(Murcia : F. Hernández, 2004) Álvarez, A.; Gómez-Urquijo, S.; Ramos, A.; Hilario, E.Our results show that cells derived from the inner cell mass (ICM) show a clear tendency to differentiate into the neural lineage, showing both cells and structures in different degrees of differentiation. Among the experimental paradigms used to learn about neural differentiation, there have been several lines of investigation on stem cells, including embryonic stem (ES) cells isolated from the inner cell mass of embryo and also stem cells derived from embryonic carcinoma (EC). In this work, we have used a cellular line obtained from the inner cell mass of a blastocyst. The cells were cultured and after inoculated subcutaneously in syngenic mice. The neural differentiation was predominant, and could be observed both by morphological and immunohistochemical methods. It was represented by neural-tubes, neurons and glial cells, as expressed by the presence of Microtubule-associated protein-2 (MAP-2) and glial fibrilary acidic protein. Moreover, tyrosine hydroxilase positive labelling was found in neuron-like cells, which suggest the chatecolaminergic differentiation. These results show that isolation of cells from the inner mass of blastocyst represents an easy, reproducible and cheap source of neural derivates suitable for both in vivo and in vitro differentiation studies.
- PublicationOpen AccessEpithelial-to-mesenchymal change of differentiation.(Murcia : F. Hernández, 1995) Guarino, M.ln embryonic morphogenesis, dramatic changes from one state of differentiation to another take place, and some epithelia transform into mesenchymal cells endowed with the ability to migrate and to form connective tissue. In vitro model systems have been developed which have provided new insights into crucial aspects of this differentiation change. Triggered perhaps by either extracellular matrix or growth factors. this phenotypic conversion involves a reorganization of the cytoskeleton, and changes in both cell-cell and cellmatrix interactions. As embryonic and adult tissues contain the same, albeit differently expressed, genetic information, one could expect, under particular circumstances, conversion to mesenchyme from epithelium to occur in adult tissues too. Indeed, there is evidence that this change really occurs in human diseases: some tissue reactions to injury: the process of tumour invasion and metastasis; and the development of carcinosarcomas, are al1 pathological conditions in which an epithelial conversion into mesenchyme probably plays a role. Here, recent observations on embryonic and in vitro epithelialmesenchymal conversion are reviewed. and these data are compared with findings from some pathological situations. Many similarities emerge which further strengthen the belief that this change in differentiation is involved in the pathogenesis, and underlies the pathological pattern of some diseases.
- PublicationOpen AccessHow does retinoic acid (RA) signaling pathway regulate spermatogenesis?(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Zhang, Hua Zhe; Hao, Shuang Li; Yang, Wan XiMale sterility is a worldwide health problem which has troubled many unfortunate families and attracted widespread attention in the field of reproduction. Retinoic acid (RA) is a metabolite of vitamin A. Previous studies have shown that insufficient intake of vitamin A can lead to male infertility. Similarly, RA-deficiency can lead to abnormal spermatogenesis in men. RA signaling is inseparable from hormone stimulation, such as FSH, testosterone and others. It can regulate spermatogenesis as well, including the proliferation and differentiation of spermatogonia, meiosis, spermiogenesis and spermiation. To promote or inhibit spermatogenesis, RA regulates Stra8, Kit, GDNF, BMP4 and other factors in various pathways. At the self-renewal stage, RA inhibits spermatogonia renewal by directly or indirectly inhibiting DMRT, GDNF and Cyclin. At the stage of differentiation and meiosis, RA controls SSC differentiation through Kit induction and Nanos2 inhibition, and controls spermatogonia meiotic entry through up- regulation of Stra8. At the stage of spermiogenesis, RARα, as a key regulator, regulates spermatogenesis by up regulating Stra8 while binding with RA. Although RA plays an important role in all stages of spermatogenesis, RA signaling is more important in the early stage of spermatogonia (spg) differentiation and spermatocyte (spc) meiosis. According to the principle of RA signaling that regulates spermatogenesis, we also speculate on the future clinical application of RA, such as potential induction of SSC in vitro, contraception and restoring spermatogenesis. This paper reviews the regulatory pathways of RA, and prospects the clinical applications of RA signaling in the future.
- PublicationOpen AccessInduction of lncRNA MALAT1 by hypoxia promotes bone formation by regulating the miR-22-3p/CEBPD axis(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Huang, Jiang; Shen, Hui liang; Feng, Ming-li; Li, Zheng; An, Shuai; Cao, Guang-leiAdaptation to hypoxia promotes fracture healing. However, the underlying molecular mechanism remains unknown. Increasing evidence has indicated that long non-coding RNAs (lncRNAs) play crucial roles in several diseases, including fracture healing. In the present study, lncRNA microarray analysis was performed to assess the expression levels of different lncRNAs in MC3T3-E1 cells cultured under hypoxic conditions. A total of 42 lncRNAs exhibited significant differences in their expression, including metastasis associated lung adenocarcinoma transcript 1 (MALAT1), maternally expressed 3, AK046686, AK033442, small nucleolar RNA host gene 2 and distal-less homeobox 1 splice variant 2. Furthermore, overexpression of MALAT1 promoted osteoblast differentiation, alkaline phosphatase (ALP) activity and matrix mineralization of MC3T3-E1 cells, whereas its knockdown diminished hypoxia-induced cell differentiation, ALP activity and matrix mineralization in these cells. Moreover, functional analysis indicated that MALAT1 regulated the mRNA and protein expression levels of CCAAT/ enhancer binding protein δ by competitively binding to microRNA-22-3p. Adenoviral-mediated MALAT1 knockdown inhibited fracture healing in a mouse model. Taken together, the results indicated that MALAT1 may serve a role in hypoxia-mediated osteogenesis and bone formation.
- PublicationOpen AccessInvolvement of gap junctional communication and connexin expression in trophoblast differentiation of the human placenta(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2001) Cronier, L.; Bastide, B.; Defamie, N.; Niger, C.; Pointis, G.; Gasc, J. M.; Malassine, A.Gap junctional intercellular communication (GJIC) permits coordinated cellular activities during development and d ifferentiation processes, and its dysfunction or mutation of connexin genes have been implicated in pathologies. In the human placenta, two distinct differentiation pathways of cytotrophoblastic cell coexist leading to a double model: fusion phenotype (villous trophoblast) a nd proliferative/ invasive phenotype (extravillous trophob last). This review focuses on current knowledge on the connexin expression and the implication of GJIC in trophoblastic differentiation. Experimental evidence obtained in human placenta demonstrates the involvement of connexin 43-gap junctions in the trophoblastic fusion process and of a connexin switch during the spatially and temporally controlled proliferation/invasion process.
- PublicationOpen Accesslnhibited differentiation of Langerhans cells in the rat epidermis upon systemic treatment with cyclosporin A(Murcia : F. Hernández, 2001) Borghi-Cirri, M.B.; Riccardi-Arbi, R.; Bacci, S.; Mori, M.; Pimpinelli, N.; Romagnoli, P.; Filipponi, F.The immunosuppressant drug cyclosporin A (CsA) is known to cause reduction in number, DNA synthesis and function of Langerhans cells (LC). Since also the differentiation of LC is known to be hampered in conditions of acquired immunodeficiency not due to drugs, we investigated whether this occurs with CsA. Rats were injected subcutaneously with CsA (5, 10 and 50 mg.kg-l.d-l) for three weeks; the skin was analyzed by Ia immunohistochemistry and by electron microscopy. Epidermal immunolabeled cells were 1553.5 (mean I SEM) per 100 basa1 keratinocytes in untreated controls and 8.7511.3, 4.7551.0 and 1.751.2 upon increasing doses of CsA (pe0.01). By electron microscopy, monocytoid cells with deep invaginations of the plasma membrane and roundish LC poor in Birbeck granules appeared in the epidermis upon treatment. The results suggest that CsA inhibits the differentiation of LC precursors in the epidermis and that this can in part explain the selective increase in the risk of skin vira1 disease and cancer in chronically treated patients.
- PublicationOpen AccessMicrogravity directs stem cell differentiation(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Chen, Zhe; Luo, Qing; Yuan, Lin; Song, Guanbiny. Stem cells are the cell of origin for organisms and their organs. These cells are critical for tissue regeneration, as well as regenerative medicine. Mechanical forces, such as gravity, have been demonstrated to provide important signals for stem cell fate. In fact, the absence of gravity, that is, microgravity, affects almost all aspects of human physiology, which has been partly attributed to changes in the biological behaviors of stem cells. In this review, we summarize the current understanding of the effects of microgravity on stem cell differentiation that control the fate of stem cells.
- PublicationOpen AccessPluripotent stem cells isolated from umbilical cord form embryonic like bodies in a mesenchymal layer culture(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Tsagias, Nikos; Kouzi-Koliakos, Kokkona; Karagianis, Vasileios; Tsikouras, P.; Koliakos, George G.Recently the matrix of umbilical cord began to use as an alternative source of stem cells additionally to the blood of umbilical cord. Umbilical cord has been used mainly for mesenchymal stem cell banking. The immunological characteristics of mesenchymal stem cells in combination with their ability to avoid rejection make them an attractive biological material for transplantations. In this study the isolation of small in size pluripotent stem cells from umbilical cord expressing early transcription factors with characteristics that resemble to embryonic stem cells is investigated. Pluripotent stem cells were isolated from human umbilical cords, by a new strategy method based on unique characteristics such as the small size and the positivity on early transcription factors OCT and Nanog. An enriched population of CXCR4+ OCT+ Nanog+ CD45- small stem cells from the cord was isolated. This fraction was able to create alkaline phosphatase positive like spheres forms in a mesenchymal layer with multilineage differentiation capacity. Our results were assessed by RT PCR and electophoresis for the pluripotent genes. These data suggest that umbilical cord provides an attractive source not only of mesenchymal stem cells but moreover of pluripotent stem cells. The method described herein should be applied in the field of stem cell banking in addition to the classical umbilical cord harvesting method. Isolation of a population of cells with pluripotent characteristics from umbilical cord. Adoption of a second centrifugation step for the pluripotent stem isolation. Increasing the value of the cord and explaining the pluripotency. This work will enhance the value of umbilical cord harvesting.
- PublicationOpen AccesspPKCδ activates SC35 splicing factor during H9c2 myoblastic differentiation(Murcia: F. Hernández, 2011) Zara, Susi; Falconi, Mirella; Rapino, Monica; Zago, Michela; Orsini, Giovanna; Mazzotti, Giovanni; Cataldi, Amelia; Teti, GabriellaAlthough Protein Kinase C (PKC) isoforms’ role in the neonatal and adult cardiac tissue development and ageing has been widely described “in vivo”, the interaction of such enzymes with specific nuclear substrates needs to be investigated. The aim of our research has been the study of the expression, localization and interaction with the splicing factor SC35 of PKC isoforms (α, δ, ε, ζ) and their potential role in modulating the transcription machinery. H9c2 cells induced to myoblast differentiation in the presence of 1% Horse Serum (HS) have represented our experimental model. The expression of PKC isoforms, their distribution and interaction with SC35 have been evaluated by western blotting, co-immunoprecipitation and double gold immunolabeling for transmission and scanning electron microscopy. Our results show PKCδ as the most expressed isoform in differentiated cells. Surprisingly, the distribution of PKCδ and SC35 does not show any significant modification between 10%FBS and 1%HS treated samples and no co-localization is observed. Moreover the interaction between the phosphorylated form of PKCδ (pPKCδ) and SC35 increases, is distributed and co-localizes within the nucleus of differentiated H9c2. These data represent reasonable evidence of pPKCδ mediated SC35 splicing factor activation, suggesting its direct effect on transcription via interaction with the transcription machinery. Furthermore, this colocalization represents a crucial event resulting in downstream changes in transcription of components which determine the morphological modifications related to cardiomyoblast differentiated phenotype.
- PublicationOpen AccessRegulatory role of microRNAs in the proliferation and differentiation of adipose-derived stem cells(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Yeong Kim, Doo; Sung, Jong HyukAdipose-derived stem cells (ASCs) are multipotent mesenchymal stem cells obtained from stromal-vascular fraction of adipose tissue. ASCs are a promising resource for cell therapy due to their simple isolation, extensive expansion potential, and low immunogenicity. ASCs repair and regenerate damaged tissue by direct differentiation, whereas many other approaches rely on the secretion of paracrine factors. miRNAs target mRNAs for cleavage or translational repression, and have been shown to play critical roles in the regulation of stem cell proliferation and differentiation. The miRNA expression profile of ASCs varies according to the isolation and culturing method, and more than 40 different miRNAs have been reported to regulate ASC proliferation and differentiation. Therefore, this review summarizes the ASC-related miRNAs and their pivotal roles in regulating the proliferation and differentiation of ASCs. A comprehensive understanding of the effects of miRNAs on the proliferation and differentiation of ASCs is important and useful to enhance the regenerative potential of ASCs.
- PublicationOpen AccessSignificados atribuidos a la educación inclusiva por la comunidad educativa(Universidad de Murcia. Servicio de Publicaciones, 2024) Arnaiz Sanchez, Pilar; Alcaraz García, Salvador; Caballero García, Carmen MaríaLa confusión existente en torno al significado de educación inclusiva supone una de las principales barreras para el progreso de este modelo educativo. El objetivo general de esta investigación es analizar los significados que diferentes agentes educativos implicados en la comunidad educativa de la Región de Murcia (España) atribuyen al concepto de educación inclusiva. Esta investigación se enmarca en un estudio descriptivo comprensivo de corte cualitativo. Han participado 74 personas involucradas en la respuesta educativa a las necesidades de aprendizaje del alumnado de centros de educación infantil, primaria y secundaria (equipos directivos y profesorado), miembros de la administración educativa, de asociaciones y estudiantes de postgrado.Para la recogida de información se emplearon técnicas cualitativas: grupos de discusión, entrevistas semiestructuradas y panel de debate. Se siguió un proceso de análisis cualitativo de contenido a través del software ATLAS.ti V.8. El estudio muestra que el concepto de educación inclusiva es conocido por los participantes, sin embargo, le atribuyen diferentes significados y enfoques. Esto determina que sea una noción poco clara y notablemente discutida entre los miembros de la comunidad educativa, lo que genera prácticas educativas de muy diferente índole y muchas veces no inclusivas.
- PublicationOpen AccessSubmucosal gland differentiation and implications in esophageal basaloid squamous cell carcinomas(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Nie, Ling; Chen, Tingting; Wu, Hongyan; Ni, Muhan; Zhou, Leying; Fan, Xiangshan; Cui, Xiaobin; Sun, QiEsophageal basaloid squamous cell carcinoma (BSCC) is a heterogenous entity with multilineage differentiation. It lacks systematical analysis on submucosal gland differentiation (SGD) due to the histological diversity and low incidence of esophageal BSCC. This study aims to find the correlation of SGD and clinicopathological features. A total of 152 esophageal BSCCs were separated into three histological groups: pure, mixed, and borderline group. The clinicopathological features were compared between different groups. The prevalence of SGD was also compared between cases of different groups. A panel of antibodies were used to identify SGD. The pure group differed from the mixed and borderline groups in many aspects, lymph node metastasis (LNM), cancer embolus, perineural invasion, and advanced stage occurred less frequently in the pure group (P<0.01). The pure group had a better but statistically insignificant overall survival (P=0.097). The squamous cell carcinoma (SCC) component or focal squamous differentiation was present in metastatic lymph nodes in almost all mixed BSCCs (95.7%, 22/23) with LNM. The LNM rate of superficial (T1b) BSCCs (17.6%, 6/34) was comparable to that of superficial (T1b) SCCs (18.5%, 57/308). However, LNM exclusively occurred in superficial mixed (3/5) and borderline (3/10) BSCCs. The IHC results demonstrated a prevalence of SGD in pure group (77%, 43/56). SGD is considered to be a favorable factor, while the squamous differentiation or invasive SCC component is an adverse factor in esophageal BSCCs. Refinement of classification is a promising way to improve patient management.
- PublicationOpen AccessTranscription factors GATA4 and TBX5 promote cardiomyogenic differentiation of rat bone marrow mesenchymal stromal cells(Universidad de Murcia. Departamento de Biología Celular e Histología, 2015) Chen, Wei; Zhang, Lei; Shao, Su-Xia; Wang, Hai-Ping; Cui, Shi-Jie; Zhang, Ya-Nan; Kong, Xiang-Zeng; Yin, Qing; Zhang, Jin-Ping. Bone marrow mesenchymal stromal cells (BMSCs) have potential applications in cell and gene therapies for cardiac disease. The cardiac-specific transcription factors GATA-binding protein 4 (GATA4) and T-Box protein 5 (TBX5) are considered to be pivotal in cardiogenesis. The aim of this study was to investigate the effects of GATA4 and TBX5 on cardiomyogenic differentiation of BMSCs. The BMSCs were initially isolated and identified. Vectors harboring cardiac transcription factor genes GATA4 and TBX5 or empty vectors were transferred into BMSCs. Cardiomyogenic cells differentiated from BMSCs were identified by expression of cardiac-specific markers including cardiac troponin T, connexin 43, β-myosin heavy chain, and myosin light chain-2 using immunocytochemical staining, western blotting, and quantitative real-time PCR. The ultrastructures of the differentiated cells were examined by transmission electron microscopy, which were similar to those of fetal cardiomyocytes. The differentiated cells exhibited L-type calcium current activities reflective of the electrophysiological characteristics of cardiomyocytes. These findings indicate that exogenous expression of cardiac-specific transcription factors GATA4 and TBX5 enhance cardiomyogenic differentiation of BMSCs
- PublicationOpen AccessVillous trophoblast of human placenta: a coherent view of its turnover, repair and contributions to villous development and maturation(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2001) Mayhew, T. M.J\ coh e re nt vicw o f hum a n v illou s trophoblast as a continuously renewing epithelium is presented. Epithelia undergoing continuous rcnewal (e.g. intestinal mucosa, epidermis) display clonogenic ce lls which pass throug h sevc ral transit di visions be fore migrating out of proliferation zones and into zones of maturati on/differenti ati on. Quantitative relations (e.g. re lati ve numbers of cells) betwee n proliferati on and diffe rentiation zones help to define the steady state and this may va ry in res po nse to ph ysi o log ic al and pathological circumstances. From the differenti ati on compartment, ce lls or ce ll fr agments arc eve ntu all y extruded by mechanisms which may involve apoptosis. All these features are seen in trophoblastic epithelium. Cy totrophobl ast ce lls (CT, proliferation zone) divide continuously throughout gestation and post-mitotic cells are recruitcd into syncytiotrophoblast (ST, diffe rentiation zone) aft cr membrane fusion. Evidence of fu sion events includes localised confluence of CT and ST cytoplasms, and intrasy ncyti al plasma membrane segments bearing desmosomal remn ants. During diffe renti ati on, nu clei undergo changes in shape, chromatin condensation and packing densit y. Densely-clustered nuclei are associated with cy tokeratin intermed iate fil aments and annul ate lamellae . Both clustered and non-clustered nuclei show ultrastructural fea tures of pre-apoptosis and apoptosis. Normall y, apoptosis is triggered only when nuclei are in the syncytium. Some (pre-)apoptotic nuclear aggregates are se qu este red in sy nc yti a l knots, extrud ed as troph obl ast fr agments into the intervill ous space and th e n depo rt ed int o th e mate rn a l c irc ul ati o n to be ph agocytosed at extrapl acental sites. During gestation, there is some constancy in the numerical ratios between CT and ST nuclei pointing to a normal steady state. The steady state may be perturbed when the epithelium is damaged loca ll y. Whe re the epithelium is denud ed, fibrin-type fibrinoid from the intervillous space plugs the discontinuity and , with CT proliferation, facilitates reepitheli alisation. Features of normal villous development (e.g. sprouting, int ervillous bridge formati on, bridge abrupt ion, sy ncytial knot formation) arc explicable in the co nt ex t of tr o ph obl ast turn ove r with ea rl y CT pro li fe rati o n be in g ma inl y fo r g row th a nd la te r proliferation for renewa l and repair. Adaptive re-settings of the epithelial steady state may also occur in abnormal pregnancies.