• 제목/요약/키워드: De-differentiation

검색결과 103건 처리시간 0.02초

Global DNA Methylation of Porcine Embryos during Preimplantation Development

  • Yeo, S.E.;Kang, Y.K.;Koo, D.B.;Han, J.S.;Yu, K.;Kim, C.H.;Park, H.;Chang, W.K.;Lee, K.K.;Han, Y.M.
    • 한국가축번식학회지
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    • 제27권4호
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    • pp.309-315
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    • 2003
  • DNA methylation at CpG sites, which is a epigenetic modification, is associated with gene expression without change of DNA sequences. During early mouse embryogenesis, dynamic changes of DNA methylation occur. In this study, DNA methylation patterns of porcine embryos produced in vivo and in vitro were examined at various developmental stages by the immunocytochemical staining method. Interestingly, active demethylation was not observed on the paternal pronucleus of porcine zygotes. However, differences were detected in the passive demethylation process between in vivo and in vitro embryos. There was no change in the DNA methylation state until the blastocyst stage of in vivo embryos, whereas partial demethylation was observed in several blastomeres from a 4 cell stage to a morula stage of in vitro embryos. The whole genome of inner cell mass (ICM) and trophectoderm (TE) cells in porcine blastocysts were evenly methylated without de novo methylation. Our findings demonstrate that genome-wide demethylation does not occur in pig embryos during preimplantation development unlike murine and bovine embryos. It indicates that the machinery regulating epigenetic reprogramming may be different between species.

Analysis and characterization of the functional TGFβ receptors required for BMP6-induced osteogenic differentiation of mesenchymal progenitor cells

  • Zhang, Yan;Zhang, De-Ying;Zhao, Yan-Fang;Wang, Jin;He, Juan-Wen;Luo, Jinyong
    • BMB Reports
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    • 제46권2호
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    • pp.107-112
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    • 2013
  • Although BMP6 is highly capable of inducing osteogenic differentiation of mesenchymal progenitor cells (MPCs), the molecular mechanism involved remains to be fully elucidated. Using dominant negative (dn) mutant form of type I and type II $TGF{\beta}$ receptors, we demonstrated that three dn-type I receptors (dnALK2, dnALK3, dnALK6), and three dn-type II receptors (dnBMPRII, dnActRII, dnActRIIB), effectively diminished BMP6-induced osteogenic differentiation of MPCs. These findings suggested that ALK2, ALK3, ALK6, BMPRII, ActRII and ActRIIB are essential for BMP6-induced osteogenic differentiation of MPCs. However, MPCs in this study do not express ActRIIB. Moreover, RNA interference of ALK2, ALK3, ALK6, BMPRII and ActRII inhibited BMP6-induced osteogenic differentiation in MPCs. Our results strongly suggested that BMP6-induced osteogenic differentiation of MPCs is mediated by its functional $TGF{\beta}$ receptors including ALK2, ALK3, ALK6, BMPRII, and ActRII.

Hyaluronic acid and proteoglycan link protein 1 suppresses platelet-derived growth factor-BB-induced proliferation, migration, and phenotypic switching of vascular smooth muscle cells

  • Dan Zhou;Hae Chan Ha;Goowon Yang;Ji Min Jang;Bo Kyung Park;Bo Kyung Park;In Chul Shin;Dae Kyong Kim
    • BMB Reports
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    • 제56권8호
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    • pp.445-450
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    • 2023
  • The development of atherosclerotic cardiovascular disease is associated with the phenotypic switching of vascular smooth muscle cells (SMCs) from a contractile to a synthetic state, leading to cell migration and proliferation. Platelet-derived growth factor-BB (PDGF-BB) modulates this de-differentiation by initiating a number of biological processes. In this study, we show that gene expression of hyaluronic acid (HA) and proteoglycan link protein 1 (HAPLN1) was upregulated during differentiation of human aortic SMCs (HASMCs) into a contractile state, but downregulated upon during PDGF-BB-induced dedifferentiation. This is the first study showing that the treatment of HASMCs with full-length recombinant human HAPLN1 (rhHAPLN1) significantly reversed PDGF-BB-induced decrease in the protein levels of contractile markers (SM22α, α-SMA, calponin, and SM-MHC), and inhibited the proliferation and migration of HASMCs induced by PDGF-BB. Furthermore, our results show that rhHAPLN1 significantly inhibited the phosphorylation of FAK, AKT, STAT3, p38 MAPK and Raf mediated by the binding of PDGF-BB to PDGFRβ. Together, these results indicated that rhHAPLN1 can suppress the PDGF-BB-stimulated phenotypic switching and subsequent de-differentiation of HASMCs, highlighting its potential as a novel therapeutic target for atherosclerosis and other vascular diseases.

HOXA9 is Underexpressed in Cervical Cancer Cells and its Restoration Decreases Proliferation, Migration and Expression of Epithelial-to-Mesenchymal Transition Genes

  • Alvarado-Ruiz, Liliana;Martinez-Silva, Maria Guadalupe;Torres-Reyes, Luis Alberto;Pina-Sanchez, Patricia;Ortiz-Lazareno, Pablo;Bravo-Cuellar, Alejandro;Aguilar-Lemarroy, Adriana;Jave-Suarez, Luis Felipe
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권3호
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    • pp.1037-1047
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    • 2016
  • HOX transcription factors are evolutionarily conserved in many different species and are involved in important cellular processes such as morphogenesis, differentiation, and proliferation. They have also recently been implicated in carcinogenesis, but their precise role in cancer, especially in cervical cancer (CC), remains unclear. In this work, using microarray assays followed by the quantitative polymerase chain reaction (qPCR), we found that the expression of 25 HOX genes was downregulated in CC derived cell lines compared with non-tumorigenic keratinocytes. In particular, the expression of HOXA9 was observed as down-modulated in CC-derived cell lines. The expression of HOXA9 has not been previously reported in CC, or in normal keratinocytes of the cervix. We found that normal CC from women without cervical lesions express HOXA9; in contrast, CC cell lines and samples of biopsies from women with CC showed significantly diminished HOXA9 expression. Furthermore, we found that methylation at the first exon of HOXA9 could play an important role in modulating the expression of this gene. Exogenous restoration of HOXA9 expression in CC cell lines decreased cell proliferation and migration, and induced an epithelial-like phenotype. Interestingly, the silencing of human papilloma virus (HPV) E6 and E7 oncogenes induced expression of HOXA9. In conclusion, controlling HOXA9 expression appears to be a necessary step during CC development. Further studies are needed to delineate the role of HOXA9 during malignant progression and to afford more insights into the relationship between downmodulation of HOXA9 and viral HPV oncoprotein expression during cercical cancer development.

"A La Recherche" of Functions for the Spore Protein SASP-E from Bacillus subtilis

  • Ruzal, Sandra M.;Bustos, Patricia L.;Sanchez-Rivas, Carmen
    • Journal of Microbiology and Biotechnology
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    • 제23권1호
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    • pp.15-21
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    • 2013
  • We previously observed that Bacillus subtilis spores from sspE mutants presented a lower germination capacity in media containing high salt concentrations (0.9M NaCl). This deficiency was attributed to the absence of SASP-E (gamma-type small-acid-soluble protein), rich in osmocompatible amino acids released by degradation. Herein we observed that, in addition, this mutant spore presented a reduced capacity to use L-alanine as germinant (L-ala pathway), required longer times to germinate in calcium dipicolinate ($Ca^{2+}$-DPA), but germinated well in asparagine, glucose, fructose, and potassium chloride (AGFK pathway). Moreover, mild sonic treatment of mutant spores partially recovered their germination capacity in L-ala. Spore qualities were also altered, since sporulating colonies from the sspE mutant showed a pale brownish color, a higher adherence to agar plates, and lower autofluorescence, properties related to their spore coat content. Furthermore, biochemical analysis showed a reduced partition in hexadecane and a higher content of $Ca^{2+}$-DPA when compared with its isogenic wild-type control. Coat protein preparations showed a different electrophoretic pattern, in particular when detected with antibodies against CotG and CotE. The complementation with a wild-type sspE gene in a plasmid allowed for recovering the wild-type coat phenotype. This is the first report of a direct involvement of SASP-E in the spore coat assembly during the differentiation program of sporulation.

Inhibition of DNA Methylation Is Involved in Transdifferentiation of Myoblasts into Smooth Muscle Cells

  • Lee, Won Jun;Kim, Hye Jin
    • Molecules and Cells
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    • 제24권3호
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    • pp.441-444
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    • 2007
  • Despite the importance of cell fate decisions regulated by epigenetic programming, no experimental model has been available to study transdifferentiation from myoblasts to smooth muscle cells. In the present study, we show that myoblast cells can be induced to transdifferentiate into smooth muscle cells by modulating their epigenetic programming. The DNA methylation inhibitor, zubularine, induced the morphological transformation of C2C12 myoblasts into smooth muscle cells accompanied by de novo synthesis of smooth muscle markers such as smooth muscle ${\alpha}$-actin and transgelin. Furthermore, an increase of p21 and decrease of cyclinD1 mRNA were observed following zebularine treatment, pointing to inhibition of cell cycle progression. This system may provide a useful model for studying the early stages of smooth muscle cell differentiation.

Proteomic Analysis of Bovine Longissimus Muscle Satellite Cells during Adipogenic Differentiation

  • Rajesh, Ramanna Valmiki;Park, Mi-Rim;Heo, Kang-Nyeong;Yoon, Du-Hak;Kim, Tae-Hun;Lee, Hyun-Jeong
    • Asian-Australasian Journal of Animal Sciences
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    • 제24권5호
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    • pp.685-695
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    • 2011
  • Satellite cells are skeletal muscle progenitor/stem cells that reside between the basal lamina and plasma membranes of skeletal fibers in vivo. These cells can give rise to both myogenic and adipogenic cells. Given the possible role for differentiation of satellite cells into adipocytes in marbling and in some pathological disorders like sarcopenia, knowledge of the proteins involved in such process remains obscure. Using two-dimensional polyacrylamide gel electrophoresis coupled with mass spectrometry, we investigated the proteins that are differentially expressed during adipogenic differentiation of satellite cells from bovine longissimus muscle. Our proteome mapping strategy to identify the differentially expressed intracellular proteins during adipogenic differentiation revealed a total of 25 different proteins. The proteins up-regulated during adipogenic differentiation of satellite cells like Cathepsin H precursor, Retinal dehydrogenase 1, Enoyl-CoA hydratase, Ubiquinol-cytochrome-c reductase, T-complex protein 1 subunit beta and ATP synthase D chain were found to be associated with lipid metabolism. The down-regulated proteins like LIM protein, annexin proteins, cofilin-1, Rho GDP-dissociation inhibitor 1 and septin-2, identified in the present study were found to be associated with myogenesis. These results clearly demonstrate that the adipogenic conversion of muscle satellite cells is associated with the up-regulated and down-regulated proteins involved in adipogenesis and myogenesis respectively.

VOLUME MEAN OPERATOR AND DIFFERENTIATION RESULTS ASSOCIATED TO ROOT SYSTEMS

  • Rejeb, Chaabane
    • 대한수학회보
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    • 제54권6호
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    • pp.1981-1990
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    • 2017
  • Let R be a root system in $\mathbb{R}^d$ with Coxeter-Weyl group W and let k be a nonnegative multiplicity function on R. The generalized volume mean of a function $f{\in}L^1_{loc}(\mathbb{R}^d,m_k)$, with $m_k$ the measure given by $dmk(x):={\omega}_k(x)dx:=\prod_{{\alpha}{\in}R}{\mid}{\langle}{\alpha},x{\rangle}{\mid}^{k({\alpha})}dx$, is defined by: ${\forall}x{\in}\mathbb{R}^d$, ${\forall}r$ > 0, $M^r_B(f)(x):=\frac{1}{m_k[B(0,r)]}\int_{\mathbb{R}^d}f(y)h_k(r,x,y){\omega}_k(y)dy$, where $h_k(r,x,{\cdot})$ is a compactly supported nonnegative explicit measurable function depending on R and k. In this paper, we prove that for almost every $x{\in}\mathbb{R}^d$, $lim_{r{\rightarrow}0}M^r_B(f)(x)= f(x)$.

Clinico-Pathologic Subtypes of Breast Cancer Primary Tumors Are Related to Prognosis after Recurrence

  • Sanchez, Cesar;Camus, Mauricio;Medina, Lidia;Oddo, David;Artigas, Rocio;Sepulveda, Alejandra Perez;Domainguez, Francisco;Razmilic, Dravna;Navarro, Maria Elena;Galindo, Hector;Acevedo, Francisco
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권12호
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    • pp.5081-5086
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    • 2016
  • Background: Pathological factors, based mainly on immunohistochemistry (IHC) and histological differentiation, are mostly used to differentiate breast cancer (BC) subtypes. Our present aim was to describe the characteristics and survival of a relapsing BC patient cohort based on clinico-pathologic subtypes determined for the primary tumors. Methods: We used a clinico- pathological definition of BC subtypes based on histological grade (HG), estrogen receptor (ER), progesterone receptor (PgR),and epidermal growth factor receptor type 2 (HER2) expression assessed by IHC. We determined variables associated with loco-regional recurrence (LRR), second primaries (SP), systemic recurrence (SR) and post-recurrence survival (PRS). Results: Out of 1,702 patients, 240 (14%) had an event defined as recurrence. Those with recurrent disease were significantly younger than those without,and were initially diagnosed at more advanced stages, with larger tumors, greater lymph nodal involvement and higher HG. With a median follow up of 61 months (1-250), 4.6% of patients without recurrence and 56.6% of patients with an event defined as recurrence had died. The median PRS for the LRR group was 77 months; 75 months for those who developed a SP and 22 months for patients with an SR (p <0.0001). In SR cases, the median PRS was shorter for ER- tumors than for ER+ tumors (15 vs. 26 months, respectively; p = 0.0019, HR 0.44; CI: 0.25-0.44). Conclusions: Subtype, defined through classic histopathologic parameters determined for primary tumors, was found to eb related to type of recurrence and also to prognosis after relapse.

섭식장애/이상섭식 여자대학운동선수와 일반여자대학생의 특성 및 위험요인 (Differentiation of Risk Factors between Female Collegiate Athletes and non-Athletes with Eating Disorders/Disordered Eating)

  • 정찬교;강형숙
    • 한국체육학회지인문사회과학편
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    • 제54권1호
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    • pp.619-629
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    • 2015
  • 이 연구의 목적은 섭식장애 증상이 있는 여자대학운동선수와 일반여자대학생의 특성을 파악하고, 위험요인을 분석하는데 있다. 378명의 운동선수와 567명의 일반여대생이 참여하였다. 각 참여자는 자기기입형 검사지(섭식장애검사지/이상섭식 검사지, SATAQ, RSES)가 사용되었다. 운동선수집단에서 22명, 221명이 각각 섭식장애와 이상섭식으로 나타났으며, 비운동선수 집단에서 22명, 205명이 섭식장애와 이상섭식으로 분류되었다. 섭식장애와 이상섭식 증상을 가지고 있는 두 집단의 특성 중 각각 6가지와 7가지 변인에서 통계적으로 유의한 차이가 있는 것으로 나타났다. 단계적 회귀분석의 결과 섭식장애/이상섭식 증상이 있는 운동선수집단과 비운동선수 집단의 위험요인은 다르게 나타났다. 마름에 대한 갈망과 자존감은 두 집단에서 필수요인이었지만, 운동선수집단에서는 신체불만족, 완벽주의, 내재화 요인 또한 주요 요인으로 나타났다. 이는 섭식장애/이상섭식을 가지고 있는 여자 대학 운동선수들이 다양한 형태의 위험요소를 가지고 있는 것이라 할 수 있다.