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Differentiation Ability (differentiation + ability)
Selected AbstractsMRG15, a component of HAT and HDAC complexes, is essential for proliferation and differentiation of neural precursor cellsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 7 2009Meizhen Chen Abstract Neurogenesis during development depends on the coordinated regulation of self-renewal and differentiation of neural precursor cells (NPCs). Chromatin regulation is a key step in self-renewal activity and fate decision of NPCs. However, the molecular mechanism or mechanisms of this regulation is not fully understood. Here, we demonstrate for the first time that MRG15, a chromatin regulator, is important for proliferation and neural fate decision of NPCs. Neuroepithelia from Mrg15 -deficient embryonic brain are much thinner than those from control, and apoptotic cells increase in this region. We isolated NPCs from Mrg15 -deficient and wild-type embryonic whole brains and produced neurospheres to measure the self-renewal and differentiation abilities of these cells in vitro. Neurospheres culture from Mrg15 -deficient embryo grew less efficiently than those from wild type. Measurement of proliferation by means of BrdU (bromodeoxyuridine) incorporation revealed that Mrg15 -deficient NPCs have reduced proliferation ability and apoptotic cells do not increase during in vitro culture. The reduced proliferation of Mrg15 -deficient NPCs most likely accounts for the thinner neuroepithelia in Mrg15 -deficient embryonic brain. Moreover, we also demonstrate Mrg15 -deficient NPCs are defective in differentiation into neurons in vitro. Our results demonstrate that MRG15 has more than one function in neurogenesis and defines a novel role for this chromatin regulator that integrates proliferation and cell-fate determination in neurogenesis during development. © 2008 Wiley-Liss, Inc. [source] Programming the genome in embryonic and somatic stem cellsJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2007Philippe Collas ,,Introduction ,,Epigenetic makeup of embryonic stem cells: keeping chromatin loose -,DNA methylation and gene expression -,CpG methylation profiles in mouse ESCs -,CpG methylation patterns in human ESCs -,Both active and inactive histone modification marks on developmentally regulated genes in ESCs suggest transcriptional activation potential -,A regulatory role of histone H1 in gene expression in embryonic stem cells? -,Polycomb group proteins impose a transcriptional brake on lineage-priming genes ,,The epigenetic makeup of mesenchymal stem cells reflects restricted differentiation potential -,CpG methylation patterns on lineage-specific promoters in adipose stem cells -,CpG content affects the relationship between promoter DNA methylation and transcriptional activity -,Bivalent histone modifications on potentially active genes? ,,Linking DNA methylation to histone modifications, chromatin packaging and (re)organization of the nuclear compartment ,,Perspectives: towards remodelling the stem cell epigenome? Abstract In opposition to terminally differentiated cells, stem cells can self-renew and give rise to multiple cell types. Embryonic stem cells retain the ability of the inner cell mass of blastocysts to differentiate into all cell types of the body and have acquired in culture unlimited self-renewal capacity. Somatic stem cells are found in many adult tissues, have an extensive but finite lifespan and can differentiate into a more restricted array of cell types. A growing body of evidence indicates that multi-lineage differentiation ability of stem cells can be defined by the potential for expression of lineage-specification genes. Gene expression, or as emphasized here, potential for gene expression, is largely controlled by epigenetic modifications of DNA and chromatin on genomic regulatory and coding regions. These modifications modulate chromatin organization not only on specific genes but also at the level of the whole nucleus; they can also affect timing of DNA replication. This review highlights how mechanisms by which genes are poised for transcription in undifferentiated stem cells are being uncovered through primarily the mapping of DNA methylation, histone modifications and transcription factor binding throughout the genome. The combinatorial association of epigenetic marks on developmentally regulated and lineage-specifying genes in undifferentiated cells seems to define a pluripotent state. [source] Effects of adenoviral-mediated coexpression of bone morphogenetic protein-7 and insulin-like growth factor-1 on human periodontal ligament cellsJOURNAL OF PERIODONTAL RESEARCH, Issue 4 2010L. Yang Yang L, Zhang Y, Dong R, Peng L, Liu X, Wang Y, Cheng X. Effects of adenoviral-mediated coexpression of bone morphogenetic protein-7 and insulin-like growth factor-1 on human periodontal ligament cells. J Periodont Res 2010; 45: 532,540. © 2010 John Wiley & Sons A/S Background and Objective:, Bone morphogenetic protein-7 (BMP-7) and insulin-like growth factor-1 (IGF-1) are important in periodontal reconstruction. However, their synergistic effect in periodontal regeneration by gene delivery has not been reported. In this study, gene delivery of these two growth factors to human periodontal ligament cells (hPDLCs) was examined for its effects on cell proliferation and differentiation. Material and Methods:, Recombinant adenoviruses containing both human BMP-7 and IGF-1 cDNA created by introducing the internal ribosome entry site (IRES) sequence were used to transfer the genes into hPDLCs. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell cycle analysis were used to observe their effects on cell proliferation, while alkaline phosphatase activity measurement, RT-PCR and in vivo tests were conducted to investigate their effects on cell differentiation. Results:, The proliferation of hPDLCs transduced by adenoviruses coexpressing BMP-7 and IGF-1 was suppressed while their differentiation ability was enhanced. There was a synergism of BMP-7 and IGF-1 in up-regulating alkaline phosphatase activity and mRNA levels of collagen type I and Runx2. Implantation in vivo with scaffolds illustrated that the transduced cells exhibited osteogenic differentiation and formed bone-like structures. Conclusion:, The combined delivery of BMP-7 and IGF-1 genes using an IRES-based strategy synergistically enhanced differentiation of hPDLCs. It is suggested that this could be a new potential method in gene therapy for periodontal reconstruction. [source] Cancer stem cell hypothesis in thyroid cancerPATHOLOGY INTERNATIONAL, Issue 9 2006Ping Zhang There is increasing evidence that many types of cancer contain their own stem cells: cancer stem cells, which are characterized by their self-renewing capacity and differentiation ability. Cancer could be regarded as an abnormal organ initiated by cancer stem cells, and cancer stem cells might play a decisive role in tumor initiation and progression. Dysregulation of stem cell self-renewal is a likely requirement for the development of cancer, and stem cells seem more likely to be the transformed target cells in carcinogenesis. This cancer stem cell model has great implications for understanding of oncogenesis and treatment for cancer. Abundant evidence suggests that, parallel to other solid tumors, cancer stem cells also exist in thyroid cancer, although their characteristics are largely unknown to date. The present review will discuss the potential traits of cancer stem cells in thyroid cancer and their transformation targets: stem cells in the thyroid gland. [source] Effect of Osteogenic Induction on the in Vitro Differentiation of Human Embryonic Stem Cells Cocultured With Periodontal Ligament FibroblastsARTIFICIAL ORGANS, Issue 11 2007Bülend Inanç Abstract:, Osteogenesis is one of the principal components of periodontal tissue development as well as regeneration. As pluripotent cells with unlimited proliferative potential and differentiation ability to all germ layer representatives, embryonic stem cells also hold the promise to become a cell source in bone tissue engineering. Our aim was to investigate osteogenic differentiation potential of human embryonic stem cells (hESCs) under the inductive influence of human periodontal ligament fibroblast (hPDLF) monolayers. After being expanded and characterized morphologically and immunohistochemically, hESCs (HUES-9) were cocultured with hPDLFs for 28 days. Two groups were established: (i) osteogenic induction group with ascorbic acid, ,-glycerophosphate, and dexamethasone containing hESC differentiation medium; and (ii) spontaneous differentiation group cultured in hESC differentiation medium. Morphological shift in cells was analyzed under an inverted microscope, and immunohistochemistry was performed on fixed specimens at days 1 and 28 using antibodies against alkaline phosphatase, osteonectin, osteopontin, bone sialoprotein (BSP), and osteocalcin (OSC). Reverse transcription,polymerase chain reaction was utilized for the detection of octameric binding protein-4, BSP, and OSC expression at mRNA level. Mineralization was assessed using alizarin red, and the surface topology shift in colonies was demonstrated with scanning electron microscopy. Results indicate the feasibility of osteogenic differentiation of hESCs in coculture, and suggest a role of periodontal ligament fibroblasts in their differentiation patterns. Advances in the field could allow for potential utilization of hESCs in periodontal tissue engineering applications involving regeneration of bone in periodontal compartment lost as a result of destructive periodontal diseases. [source] Antibody-immobilized column for quick cell separation based on cell rollingBIOTECHNOLOGY PROGRESS, Issue 2 2010Atsushi Mahara Abstract Cell separation using methodological standards that ensure high purity is a very important step in cell transplantation for regenerative medicine and for stem cell research. A separation protocol using magnetic beads has been widely used for cell separation to isolate negative and positive cells. However, not only the surface marker pattern, e.g., negative or positive, but also the density of a cell depends on its developmental stage and differentiation ability. Rapid and label-free separation procedures based on surface marker density are the focus of our interest. In this study, we have successfully developed an antiCD34 antibody-immobilized cell-rolling column, that can separate cells depending on the CD34 density of the cell surfaces. Various conditions for the cell-rolling column were optimized including graft copolymerization, and adjustment of the column tilt angle, and medium flow rate. Using CD34-positive and -negative cell lines, the cell separation potential of the column was established. We observed a difference in the rolling velocities between CD34-positive and CD34-negative cells on antibody-immobilized microfluidic device. Cell separation was achieved by tilting the surface 20 degrees and the increasing medium flow. Surface marker characteristics of the isolated cells in each fraction were analyzed using a cell-sorting system, and it was found that populations containing high density of CD34 were eluted in the delayed fractions. These results demonstrate that cells with a given surface marker density can be continuously separated using the cell rolling column. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010 [source] Histone deacetylase inhibitors trichostatin A and valproic acid circumvent apoptosis in human leukemic cells expressing the RUNX1 chimeraCANCER SCIENCE, Issue 2 2008Ko Sasaki Disturbance of the normal functions of wild-type RUNX1 resulting from chromosomal translocations or gene mutations is one of the major molecular mechanisms in human leukemogenesis. RUNX1-related chimeras generated by the chromosomal translocations repress transcriptional activity of wild-type RUNX1 by recruiting the co-repressor/histone deacetylase complex. Thus, histone deacetylase inhibitors are expected to restore normal functions of wild-type RUNX1 and thereby affect the growth and differentiation ability of leukemic cells expressing the chimera. We investigated the in vitro effects of histone deacetylase inhibitors, trichostatin A and valproic acid, on human leukemic cell lines such as SKNO-1 and Kasumi-1 expressing RUNX1/ETO, Reh expressing TEL/RUNX1 and SKH-1 co-expressing RUNX1/EVI1 and BCR/ABL. We also employed K562 cells expressing BCR/ABL without such a chimera as a control. Treatment with each inhibitor increased acetylated histone 4 in all of these cell lines. Interestingly, proliferation of SKNO-1, Kasumi-1, SKH-1 and Reh cells was significantly suppressed after 3-day culture with trichostatin A or valproic acid, when compared to that of K562 cells. We observed cell cycle arrest and apoptotic induction in the RUNX1 chimera-expressing cells by the propidium iodide staining. Up- and downregulation of cell cycle regulator genes appeared to be the molecular basis for the former, and activation of both extrinsic and intrinsic apoptotic caspases for the latter. We propose histone deacetylase inhibitors to be an attractive choice in the molecular targeting therapy of RUNX1-related leukemia. (Cancer Sci 2008; 99: 414,422) [source] | |||||||||||||