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Jin Young Huh,
Jong In Kim,
Yoon Jeong Park,
In Jae Hwang,
Yun Sok Lee,
Jee Hyung Sohn,
Sung Kyu Lee,
Assim A Alfadda,
Su Sung Kim,
Sung Hee Choi,
Dong-Sup Lee,
Se-Ho Park, Rho Hyun Seong,
Cheol Soo Choi,
Jae Bum Kim
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ABSTRACT: Systemic low-grade chronic inflammation has been intensively investigated in obese subjects. Recently, various immune cell types, such as macrophages, granulocytes, helper T cells, cytotoxic T cells, and B cells, have been implicated in the pathogenesis of adipose tissue inflammation. However, the roles of invariant natural killer T cells (iNKT cells) and the regulation of iNKT cell activity in adipose tissue are not thoroughly understood. Here, we demonstrated that iNKT cells were decreased in number in the adipose tissue of obese subjects. Interestingly, CD1d, a molecule involved in lipid antigen presentation to iNKT cells, was highly expressed in adipocytes and CD1d-expressing adipocytes stimulated iNKT cell activity through physical interaction. iNKT cell population and CD1d expression were reduced in the adipose tissue of obese mice and humans compared to those of lean subjects. Moreover, iNKT cell-deficient Jα18 knockout mice became more obese and exhibited increased adipose tissue inflammation at the early stage of obesity. These data suggest that adipocytes regulate iNKT cell activity via CD1d and that the interaction between adipocytes and iNKT cells may modulate adipose tissue inflammation in obesity.
Molecular and cellular biology 11/2012; · 6.06 Impact Factor
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ABSTRACT: The entrance of influenza virus into host cells is facilitated by the attachment of the globular region of viral hemagglutinin to the sialic acid receptors on host cell surfaces. In this study, we have cloned the cDNA fragment encoding the entire globular region (residues 101-257) of hemagglutinin of the H9N2 type avian influenza virus (A/ck/Korea/ms96/96). The protein segment (denoted as the H9 peptide), which was expressed and purified in E. coli, was used for the immunization of BALB/c mice to obtain the anti-H9 antiserum. To identify specific DNA aptamers with high affinity to H9 peptide, we conducted the SELEX method; 19 aptamers were newly isolated. A random mixture of these aptamers showed an increased level of binding affinity to the H9 peptide. The sequence alignment analysis of these aptamers revealed that 6 aptamers have highly conserved consensus sequences. Among these, aptamer C7 showed the highest similarity to the consensus sequences. Therefore, based on the C7 aptamer, we synthesized a new modified aptamer designated as C7-35M. This new aptamer showed strong binding capability to the viral particles. Furthermore, it could prevent MDCK cells from viral infection by strong binding to the viral particles. These results suggest that our aptamers can recognize the hemagglutinin protein of avian influenza virus and inhibit the binding of the virus to target receptors required for the penetration of host cells.
Molecules and Cells 11/2011; 32(6):527-33. · 2.18 Impact Factor
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ABSTRACT: Despite the recent identification of surface markers of undifferentiated human embryonic stem cells (hESCs), the crucial cell-surface molecules that regulate the self-renewal capacity of hESCs remain largely undefined. Here, we generated monoclonal antibodies (MAbs) that specifically bind to undifferentiated hESCs but not to mouse embryonic stem cells. Among these antibodies, we selected a novel MAb, 4-63, and identified its target antigen as the L1 cell adhesion molecule (L1CAM) isoform 2. Notably, L1CAM expressed in hESCs lacked the neuron-specific YEGHH and RSLE peptides encoded by exons 2 and 27, respectively. L1CAM colocalized with hESC-specific cell-surface markers, and its expression was markedly downregulated on differentiation. Stable L1CAM depletion markedly decreased hESC proliferation, whereas L1CAM overexpression increased proliferation. In addition, the expression of octamer-binding transcription factor 4, Nanog, sex-determining region Y-box 2, and stage-specific embryonic antigen (SSEA)-3 was markedly downregulated, whereas lineage-specific markers and SSEA-1 were upregulated in L1CAM-depleted hESCs. Interestingly, the actions of L1CAM in regulating the proliferation and differentiation of hESCs were exerted predominantly through the fibroblast growth factor receptor 1 signaling pathway. Taken together, our results suggest that L1CAM is a novel cell-surface molecule that plays an important role in the maintenance of self-renewal and pluripotency in hESCs.
Stem Cells 09/2011; 29(12):2094-9. · 7.78 Impact Factor
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ABSTRACT: The SWI/SNF chromatin-remodeling complex has been implicated in the activation and proliferation of T cells. After T cell receptor signaling, the SWI/SNF complex rapidly associates with chromatin and controls gene expression in T cells. However, the process by which the SWI/SNF complex regulates peripheral T cell activation has not been elucidated. In this study, we show that the SWI/SNF complex regulates cytokine production and proliferation of T cells. During T cell activation, the SWI/SNF complex is recruited to the promoter of the transcription factor AP-1, and it increases the expression of AP-1. Increased expression of the SWI/SNF complex resulted in enhanced AP-1 activity, cytokine production, and proliferation of peripheral T cells, whereas knockdown of the SWI/SNF complex expression impaired the AP-1 expression and reduced the activation and proliferation of T cells. Moreover, mice that constitutively expressed the SWI/SNF complex in T cells were much more susceptible to experimentally induced autoimmune encephalomyelitis than the normal mice were. These results suggest that the SWI/SNF complex plays a critical role during T cell activation and subsequent immune responses.
Journal of Biological Chemistry 11/2009; 285(4):2340-50. · 4.77 Impact Factor
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ABSTRACT: The SWI/SNF chromatin-remodeling complex functions as a transcriptional regulator and plays a significant role in cell proliferation, differentiation and embryonic development. SRG3, a homologue of human BAF155, is a core component of the mouse SWI/SNF chromatin remodeling complex. Mutant mice deficient in Srg3 expression are peri-implantation lethal. To investigate the role of SRG3 in the post-implantation stage, we generated SRG3 transgene-rescued (Srg3-/-Tg+) embryos by inducing exogenous gene expression. These Srg3-/-Tg+ embryos overcame early embryonic lethality and extended the life span until mid-gestation. However, the embryos displayed significant defects in blood vessel formation and fetal circulation within the yolk sac around embryonic day 10.5, which led to developmental retardation and death. We found that SRG3 expression was absent in the visceral endoderm of Srg3-/-Tg+ yolk sacs, while SRG3 was normally expressed in wild-type embryos. In addition, expression of angiogenesis-related genes, including Angiopoietin1, Tie2, EphrinB2, Ihh and Notch1, was markedly reduced in Srg3-/-Tg+ yolk sacs. During normal angiogenesis, maturation of the visceral endoderm development is observed in the yolk sac. However, in Srg3-/-Tg+ yolk sacs, the visceral endoderm did not develop normally. Our results indicate that SRG3 is required for angiogenesis and visceral endoderm development in the yolk sac.
Developmental Biology 04/2008; 315(1):136-46. · 4.07 Impact Factor
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ABSTRACT: Insulin plays a critical role in whole-body energy homeostasis by regulating lipid and glucose metabolism. In fat and liver tissues, ADD1/SREBP1c is a key transcription factor to mediate insulin-dependent regulation of gene expression. Although transcriptional and proteolytic activation of ADD1/SREBP1c has been studied intensively, the mechanism by which insulin regulates expression of its target genes with ADD1/SREBP1c at the chromatin level is unclear. Here, we reveal that SWI/SNF chromatin remodeling factors interact with the ADD1/SREBP1c and actively regulate insulin-dependent gene expression. Insulin enhanced recruitment of SWI/SNF chromatin remodeling factors to its target gene promoters with concomitant changes in the chromatin structures as well as gene expression. Furthermore, in vivo overexpression of BAF155/SRG3, a component of the SWI/SNF complex, substantially promoted insulin target gene expression and insulin sensitivity. Taken together, our results suggest that the SWI/SNF chromatin remodeling complexes confer not only insulin-dependent gene expression but also insulin sensitivity in vivo via interaction with ADD1/SREBP1c.
Molecular and Cellular Biology 02/2007; 27(2):438-52. · 5.53 Impact Factor
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ABSTRACT: MOTIVATION: An important issue in stem cell biology is to understand how to direct differentiation towards a specific cell type. To elucidate the mechanism, previous studies have focused on identifying the responsible gene regulators, which have, however, failed to provide a systemic view of regulatory modules. To obtain a unified description of the regulatory modules, we characterized major stem cell species by employing a co-clustering latent variable model (LVM). The LVM-based method allowed us to elucidate the cell type-specific transcription factors, using genomic sequences as well as expression profiles. RESULTS: We used a list of genes enriched in each of 21 stem cell subpopulations, and their upstream genomic sequences. The LVM-based study allowed us to uncover the regulatory modules for each stem cell cluster, e.g. GABP and E2F for the proliferation phase, and Ap2alpha and Ap2gamma for the quiescence phase. Furthermore, the identities of the stem cell clusters were well revealed by the constituent genes that were directly targeted by the modules. Consequently, our analytical framework was demonstrated to be useful through a detailed case study of stem cell differentiation and can be applied to problems with similar characteristics.
Bioinformatics 09/2006; 22(16):2005-11. · 5.47 Impact Factor
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Bioinformatics. 01/2006; 22:2005-2011.
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Yeon Sung Son,
Jae Hyun Park,
Young Kook Kang,
Jin-Sung Park,
Hong Seo Choi,
Ji Young Lim,
Jeoung Eun Lee,
Jung Bok Lee,
Myoung Seok Ko,
Yong-Sam Kim,
Jeong-Heon Ko,
Hyun Soo Yoon,
Kwang-Woong Lee, Rho Hyun Seong,
Shin Yong Moon,
Chun Jeih Ryu Ph.D,
Hyo Jeong Hong Ph.D
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ABSTRACT: The cell-surface markers used routinely to define the undifferentiated state and pluripotency of human embryonic stem cells (hESCs) are those used in mouse embryonic stem cells (mESCs) because of a lack of markers directly originated from hESC itself. To identify more hESC-specific cell-surface markers, we generated a panel of monoclonal antibodies (MAbs) by immunizing the irradiated cell clumps of hESC line Miz-hES1, and selected 26 MAbs that were able to bind to Miz-hES1 cells but not to mESCs, mouse embryonic fibroblast cells, and STO cells. Most antibodies did not bind to human neural progenitor cells derived from the Miz-hES1 cells, either. Of these, MAb 20-202S (IgG1, κ) immunoprecipitated a cell-surface protein of 72-kDa from the lysate of biotin-labeled Miz-hES1 cells, which was identified to be heat shock 70-kDa protein 8 isoform 1 (HSPA8) by quadrupole time-of-flight tandem mass spectrometry. Immunocytochemical analyses proved that the HSPA8 protein was also present on the surface of hESC lines Miz-hES4, Miz-hES6, and HSF6. Two-color flow cytometric analysis of Miz-hES1 and HSF6 showed the coexpression of the HSPA8 protein with other hESC markers such as stage-specific embryonic antigen 3 (SSEA3), SSEA4, TRA-1-60, and TRA-1-81. Flow cytometric and Western blot analyses using various cells showed that MAb 20-202S specifically bound to the HSPA8 protein on the surface of Miz-hES1, contrary to other anti-HSP70 antibodies examined. Furthermore, the surface expression of the HSPA8 protein on Miz-hES1 was markedly downregulated upon differentiation. These data indicate that a novel MAb 20-202S recognizes the HSPA8 protein on the surface of hESCs and suggest that the HSPA8 protein is a putative cell-surface marker for undifferentiated hESCs.
Stem Cells 10/2005; 23(10):1502 - 1513. · 7.78 Impact Factor
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ABSTRACT: The SWI3-related gene product (SRG3), a component of the mouse SWI/SNF complex, has been suggested to have an alternative function. Here, we demonstrate that in the prostate transactivation of the androgen receptor (AR) is modulated by SRG3 in multiple ways. The expression of SRG3, which is developmentally regulated in the prostate, is induced by androgen through AR. SRG3 in turn enhances the transactivation of AR, providing a positive feedback regulatory loop. The SRG3 coactivation of AR transactivation is achieved through the recruitment of coactivator SRC-1, the protein level of which is upregulated by SRG3, providing another pathway of positive regulation. Interestingly, SRG3 coactivation of AR transactivation is fully functional in BRG1/BRM-deficient C33A cells and the AR/SRG3/SRC-1 complex formed in vivo contains neither BRG1 nor BRM protein, suggesting the possibility of an SRG3 function independent of the SWI/SNF complex. Importantly, the AR/SRG3/SRC-1 complex occupies androgen response elements on the endogenous SRG3 and PSA promoter in an androgen-dependent manner in mouse prostate and LNCaP cells, respectively, inducing gene expression. These results suggest that the multiple positive regulatory mechanisms of AR transactivation by SRG3 may be important for the rapid proliferation of prostate cells during prostate development and regeneration.
Molecular and Cellular Biology 07/2005; 25(12):4841-52. · 5.53 Impact Factor
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ABSTRACT: Adipocyte determination and differentiation dependent factor 1 (ADD1)/sterol regulatory element binding protein isoform (SREBP1c) is a key transcription factor in fatty acid metabolism and insulin- dependent gene expression. Although its transcriptional and post-translational regulation has been extensively studied, its regulation by interacting proteins is not well understood. To identify cellular proteins that associate with ADD1/SREBP1c, we employed the yeast two-hybrid system with an adipocyte cDNA library. Using the N-terminal domain of ADD1/SREBP1c as bait, we identified Twist2 (also known as Dermo-1), a basic helix-loop-helix (bHLH) protein, as a novel ADD1/SREBP1c interacting protein. Over-expression of Twist2 strongly repressed the transcriptional activity of ADD1/SREBP1c, primarily by reducing its binding to target sequences. Inhibition of histone deacetylase (HDAC) activity with HDAC inhibitors relieved this repression. Our data suggest that physical interaction between Twist2 and ADD1/SREBP1c attenuates transcriptional activation by ADD1/SREBP1c by inhibiting its binding to DNA, and that this inhibition is at least partly dependent on chromatin modification by HDACs.
Nucleic Acids Research 01/2004; 31(24):7165-74. · 8.03 Impact Factor
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ABSTRACT: In eukaryotes, Rad51 and Rad52 are two key components of homologous recombination and recombinational repair. These two proteins interact with each other. Here we investigated the role of interaction between Rhp51 and Rad22, the fission yeast homologs of Rad51 and Rad52, respectively, on the function of each protein. We identified a direct association between the two proteins and their self-interactions both in vivo and in vitro. We also determined the binding domains of each protein that mediate these interactions. To characterize the role of Rhp51-Rad22 interaction, we used random mutagenesis to identify the mutants Rhp51 and Rad22, which cannot interact each other. Interestingly, we found that mutant Rhp51 protein, which cannot interact with either Rad22 or Rti1 (G282D), lost its DNA repair ability. In contrast, mutant Rad22 proteins, which cannot specifically bind to Rhp51 (S379L and P381L), maintained their DNA repair ability. These results suggest that the interaction between Rhp51 and Rad22 is crucial for the recombinational repair function of Rhp51. However, the significance of this interaction on the function of Rad22 remains to be characterized further.
Journal of Biological Chemistry 09/2002; 277(33):30264-70. · 4.77 Impact Factor
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ABSTRACT: Hrp3, a paralog of Hrp1, is a novel member of the CHD1 (chromo-helicase/ATPase-DNA binding 1) protein family of Schizosaccharomyces pombe. Although it has been considered that CHD1 proteins are required for chromatin modifications in transcriptional regulations, little is known about their roles in vivo. In this study, we examined the effects of Hrp3 on heterochromatin silencing using several S. pombe reporter strains. The phenotypic analysis revealed that hrp3(+) is not an essential gene for cell viability. However, Hrp3 is required for transcriptional repression at silence loci of mat3. A chromatin immunoprecipitation assay showed that Hrp3 directly associates with mat3 chromatin. Thus, our results strongly suggest that Hrp3 is involved in heterochromatin silencing and plays a direct role as a chromatin remodeling factor at mat3 in vivo.
Biochemical and Biophysical Research Communications 08/2002; 295(4):970-4. · 2.48 Impact Factor
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ABSTRACT: We expressed the allogenic class II MHC antigen and B7.1 (CD80) co-stimulatory molecule in A20 beta-lymphoma cells in order to test their efficacy as immuno-stimulating adjuvant agents in inducing tumor-specific immunity. The transduction of the allogenic I-Ab alpha and beta chain genes into A20 cell resulted in a surface expression of the allogenic class II MHC molecules. The expression of the allogenic class II MHC antigen (I-Ab) in A20 cells enhanced the proliferation of T cells in a mixed lymphocyte tumor culture and in vitro cytotoxic T lymphocyte (CTL) generation against parental cells. The B7.1 gene, which is known to be a potent co-stimulatory molecule, was also transduced and expressed in A20 cells, either alone or in combination with I-Ab. The B7.1 transduction alone leads to a similar in vitro immune enhancing effect as I-Ab. When both the I-Ab and B7.1 genes were transduced, the in vitro immunostimulating capacity was further enhanced. Finally, we also tested the A20 cells that were transduced with I-Ab and/or B7.1 for their efficacy as preventive tumor vaccines in vivo. The results indicate that the A20 cells that express both the I-Ab and B7.1 have more potent vaccinating potential, compared to the cells that express only one of the molecules.
Molecules and Cells 03/2002; 13(1):130-6. · 2.18 Impact Factor
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ABSTRACT: Hepatitis C virus (HCV) is a positive strand RNA virus of the Flaviviridae family and the major cause of post‐transfusion non‐A, non‐B hepatitis. Vaccine development for HCV is essential but has been slowed by poor understanding of the type of immunity that naturally terminates HCV infection. The DNA‐based immunization technique offers the potential advantage of including cellular immune responses against conserved internal proteins of a virus, as well as the generation of antibodies to viral surface proteins. Here, we demonstrate that cell lines expressing the HCV core and/or NS3 proteins can induce a specific CTL response in mice, and these results suggest a possibility that the HCV core and NS3 DNA can be used to induce CTL activity against the antigen in mice and can be further developed as a therapeutic and preventive DNA vaccine.
Korean journal of biological sciences 01/1999; 3(3):337-341.
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ABSTRACT: The Schizosaccharomyces pombe uvi31+ gene has been previously isolated as a UV-inducible gene [Lee JK et al. (1994) Biochem Biophys Res Commun 202:1113–1119]. This gene encodes a protein of about 12 kDa with 57% amino acid sequence similarity to Escherichia coli BolA protein which is known to be involved in switching between the cell elongation and septation systems during the cell division cycle. The putative Mlul cell cycle box (MCB), SWI4/6-dependent cell cycle box (SCB), and gear-box elements are found in the upstream region of uvi31+ gene, suggesting that this gene shows the cell cycle-regulated and growth phase-dependent expression. Interestingly, the level of uvi31− transcript varies throughout the cell cycle, peaking in G1 phase before septation, and also shows the growth phase-dependent pattern during cellular growth, increasing maximally at the diauxic shift phase just before stationary phase. Furthermore, the transcript level of this gene is raised after S phase arrest, and is also increased maximally at 4 hr after UV irradiation of 240 J/m2. These results suggest that the delayed induction of uvi31+ gene after UV irradiation may be caused by cell cycle control of this gene after DNA replication checkpoint arrest. Thus, the uvi31+ gene may play a role in controlling the progress of the cell cycle after DNA damage (UV irradiation). Environ. Mol. Mutagen. 30:72–81, 1997 © 1997 Wiley-Liss, Inc.
Environmental and Molecular Mutagenesis 12/1998; 30(1):72 - 81. · 3.71 Impact Factor
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ABSTRACT: The TcfA (T cell specific factor‐1) is a transcription factor uniquely expressed in T‐lineage cells. Its expression is developmentally regulated, which is high in the specific stage of immature thymocytes, but is much lower in mature T cells. We cloned the TcfA gene by subtractive hybridization and found it to be highly expressed in the thymus compared to the mRNA level in the spleen as expected. Since apoptosis occurs enormously in the thymus, we were interested in whether TcfA gene expression could be regulated by such a high level of apoptotic assault. By using T cell hybridoma 70.7 cells, we induced apoptosis by incubating cells with anti‐CD3 antibody in vitro. After apoptosis induction, TcfA mRNA level was found to be significantly reduced compared to normal cells. Since TcfA is a transcription factor for the CD3‐E gene, we tested how CD3‐E expression is regulated in apoptotic cells. The surface level of CD3‐E protein is also down‐regulated after apoptosis induction. Such a down‐modulation of CD3‐E protein would reduce the TCR/CD3 complex on the cell surface, which would be an important regulator for T cell apoptosis
Korean journal of biological sciences 01/1998; 2(3):403-410.
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ABSTRACT: Hrp1, of Schizosaccharomyces pombe, is a new member of the SWI2/SNF2 protein family that contains a chromodomain and a DNA binding domain as well as ATPase/7 helicase domains. This configuration suggests that Hrp1 could be a homolog of mouse CHD1, which is thought to function in altering the chromatin structure to facilitate gene expression. To understand the enzymatic nature of Hrp1, we purified the 6‐Histidine‐tagged Hrp1 protein (6×His‐Hrp1) to homogeneity from a S. pombe Hrp1‐overexpressing strain and then examined its biochemical properties. We demonstrate that the purified 6×His‐Hrp1 protein exhibited a DNA‐binding activity with a moderate preference to the (A+T)‐rich tract in double‐stranded DNA via a minor groove interaction. However, we failed to detect any intrinsic DNA helicase activity from the purified Hrp1 like other SWI2/SNF2 proteins. These observations suggest that the DNA binding activities of Hrp1 may be involved in the remodeling of the chromatin structure with DNA‐dependent ATPase. We propose that Hrp1 may function in heterochromatins as other proteins with a chromo‐ or ATPase/helicase domain and play an important role in the determination of chromatin architecture
Korean journal of biological sciences 01/1998; 2(4):539-543.
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Yeon Sung Son,
Jae Hyun Park,
Young Kook Kang,
Jin-Sung Park,
Hong Seo Choi,
Ji Young Lim,
Jeoung Eun Lee,
Jung Bok Lee,
Myoung Seok Ko,
Yong-Sam Kim,
Jeong-Heon Ko,
Hyun Soo Yoon,
Kwang-Woong Lee, Rho Hyun Seong,
Shin Yong Moon,
Chun Jeih Ryu,
Hyo Jeong Hong
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ABSTRACT: The cell-surface markers used routinely to define the undifferentiated state and pluripotency of human embryonic stem cells (hESCs) are those used in mouse embryonic stem cells (mESCs) because of a lack of markers directly originated from hESC itself. To identify more hESC-specific cell-surface markers, we generated a panel of monoclonal antibodies (MAbs) by immunizing the irradiated cell clumps of hESC line Miz-hES1, and selected 26 MAbs that were able to bind to Miz-hES1 cells but not to mESCs, mouse embryonic fibroblast cells, and STO cells. Most antibodies did not bind to human neural progenitor cells derived from the Miz-hES1 cells, either. Of these, MAb 20-202S (IgG1, kappa) immunoprecipitated a cell-surface protein of 72-kDa from the lysate of biotin-labeled Miz-hES1 cells, which was identified to be heat shock 70-kDa protein 8 isoform 1 (HSPA8) by quadrupole time-of-flight tandem mass spectrometry. Immunocytochemical analyses proved that the HSPA8 protein was also present on the surface of hESC lines Miz-hES4, Miz-hES6, and HSF6. Two-color flow cytometric analysis of Miz-hES1 and HSF6 showed the coexpression of the HSPA8 protein with other hESC markers such as stage-specific embryonic antigen 3 (SSEA3), SSEA4, TRA-1-60, and TRA-1-81. Flow cytometric and Western blot analyses using various cells showed that MAb 20-202S specifically bound to the HSPA8 protein on the surface of Miz-hES1, contrary to other anti-HSP70 antibodies examined. Furthermore, the surface expression of the HSPA8 protein on Miz-hES1 was markedly downregulated upon differentiation. These data indicate that a novel MAb 20-202S recognizes the HSPA8 protein on the surface of hESCs and suggest that the HSPA8 protein is a putative cell-surface marker for undifferentiated hESCs.
Stem Cells 23(10):1502-13. · 7.78 Impact Factor
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ABSTRACT: The rhp51+ gene encodes three transcripts of 1.9, 1.6 and 1.3 kb which have at least six polyadenylation sites. Primer-extension analysis revealed that two transcription start points (tsp) at -166 and -136 were responsible for the DNA damage inducibility of this gene. Northern blot analyses showed that the three transcripts were expressed differentially in response to a variety of DNA damage. During the mitotic cell cycle, only the largest transcript exhibited periodic expression, reaching the maximal level in front of the cdc22+ transcript which peaks at the G1/S boundary. Unexpectedly, the steady-state levels of the three transcripts were differentially regulated during the growth cycle. The largest and smallest transcripts accumulated in large quantity at the diauxic shift and during the entry into stationary phase, respectively. To localize the regions responsible for the differential expression of rhp51 +, we constructed rhp51::ura4 and ura4::rhp51 hybrid genes, and analyzed their expression patterns in response to methyl methanesulfonate (MMS)-induced DNA damage. The results showed that the promoter region and 5' half of rhp51+ are sufficient to confer damage-responsiveness while the 3′ end of the gene alone can direct the formation of multiple, discrete 3' ends of the transcripts. From these results, we conclude that this novel one gene-multiple product system is possible through the cooperation of both the promoter and 3' terminal regions
Gene 169(1):125-130. · 2.34 Impact Factor
