• BMB Reports
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• 제57권4호
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• pp.182-187
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• 2024

Neural stem cells (NSCs) in the adult hippocampus divide infrequently; the endogenous molecules modulating adult hippocampal neurogenesis (AHN) remain largely unknown. Here, we show that ErbB3 binding protein 1 (Ebp1), which plays important roles in embryonic neurodevelopment, acts as an essential modulator of adult neurogenic factors. In vivo analysis of Ebp1 neuron depletion mice showed impaired AHN with a low number of hippocampal NSCs and neuroblasts. Ebp1 leads to transcriptional repression of Bmp4 and suppression of Ascl1 promoter methylation in the dentate gyrus of the adult hippocampus reflecting an unusually high level of Bmp4 and low Ascl1 level in neurons of Ebp1-deficient mice. Therefore, our findings suggests that Ebp1 could act as an endogenous modulator of the interplay between Bmp4 and Ascl1/Notch signaling, contributing to AHN.

• Asian-Australasian Journal of Animal Sciences
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• 제20권10호
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• pp.1485-1489
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• 2007

Achaete-scute like 2 (ASCL2) gene encodes a member of the basic helix-loop-helix transcription factor which is essential for the maintenance of proliferating trophoblasts during placental development. ASCL2 gene preferentially expresses the maternal allele in the mouse. However, it escapes genomic imprinting in the human. In this study, the complete open reading frame consisting of 193 amino acids of ASCL2 gene was obtained. Sequence analysis indicated that a C-G mutation existed in the 3' region between Meishan and Large White pigs. The polymorphism was used to determine the monoallelic or biallelic expression with RT-PCR-RFLP in pigs of Large $White{\times}Meishan$ $F_1$ hybrids. Imprinting analysis indicated that the ASCL2 gene expression was biallelic in all the tested tissues (heart, liver, spleen, lung, kidney, stomach, small intestine, skeletal muscle, fat, uterus, ovary and pituitary). PCR-RFLP was used to detect the polymorphism in 270 pigs of the "$Large\;White{\times}Meishan$" $F_2$ resource population. The statistical results showed highly significant associations of the genotypes and fat meat percentage (FMP), lean meat percentage (LMP) and ratio of lean to fat (RLF) (p<0.01), and significant associations of the genotypes and loin eye area (LEA) and internal fat rate (IFR) (p<0.05).

• 대한시과학회지
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• 제20권4호
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• pp.469-482
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• 2018

목적 : 비구면 디자인의 소프트 콘택트렌즈 ASCL(aspheric soft contact lens)로 굴절교정을 한 젊은 성인 근시안에서 콘택트렌즈 착용 후 안구의 구면수차와 코마수차 변화를 확인하였다. 방법 : 건강한 성인 근시안 50명(평균 연령: $23.15{\pm}1.70$세, 평균 등가구면굴절력: $-2.90{\pm}1.75D$)을 대상으로 굴절교정용 ASCL(Biotrue, Bausch+Lomb, USA)을 착용시킨 후 검사실의 조도 100 lx에서 고위수차와 동공크기를 측정하였다. 고위수차는 Wavefront Analyzer를 사용하여 동공크기 4 mm 영역에서 측정하였고, 동공크기는 Pupillometer를 이용하여 3.5 m 거리의 물체를 주시하도록 한 후 암소시(scotopic condition, light off) 상태에서 측정하였다. 결과 : 20대 근시안의 구면수차와 코마수차는 $0.026{\pm}0.031{\mu}m$, $0.078{\pm}0.039{\mu}m$, ASCL 착용 후에는 $0.019{\pm}0.026{\mu}m$ and $0.082{\pm}0.038{\mu}m$로 구면수차는 감소하고 코마수차는 유의하게 증가하였다. 대상안 중 구면수차가 감소한 경우는 전체의 68%로 양의 구면수차를 갖는 대상안에서 감소하였고, 증가한 경우는 11%로 음의 구면수차를 갖는 대상안에서 증가하였다. 코마수차는 대상안의 53%에서 증가하였고 19%에서는 변함이 없었으며 28%에서 감소하였다. 약도 및 중등도 근시안에서 구면수차는 근시도와 상관성이 없었고, 코마수차는 근시도가 높을수록 큰 것으로 나타났다. 결론 : 조절자극이 없는 암소시 상태에서 ASCL 착용 후 안구의 구면수차는 양의 값을 갖는 경우에는 감소하지만 음의 값을 갖는 경우에는 증가하였고, 이는 ASCL 디자인과 동공크기가 영향을 준 것으로 생각된다.

• Biomolecules & Therapeutics
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• 제31권3호
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• pp.264-275
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• 2023

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by tremors, bradykinesia, and rigidity. PD is caused by loss of dopaminergic (DA) neurons in the midbrain substantia nigra (SN) and therefore, replenishment of DA neurons via stem cell-based therapy is a potential treatment option. Astrocytes are the most abundant non-neuronal cells in the central nervous system and are promising candidates for reprogramming into neuronal cells because they share a common origin with neurons. The ability of neural progenitor cells (NPCs) to proliferate and differentiate may overcome the limitations of the reduced viability and function of transplanted cells after cell replacement therapy. Achaete-scute complex homolog-like 1 (Ascl1) is a well-known neuronal-specific factor that induces various cell types such as human and mouse astrocytes and fibroblasts to differentiate into neurons. Nurr1 is involved in the differentiation and maintenance of DA neurons, and decreased Nurr1 expression is known to be a major risk factor for PD. Previous studies have shown that direct conversion of astrocytes into DA neurons and NPCs can be induced by overexpression of Ascl1 and Nurr1 and additional transcription factors genes such as superoxide dismutase 1 and SRY-box 2. Here, we demonstrate that astrocytes isolated from the ventral midbrain, the origin of SN DA neurons, can be effectively converted into DA neurons and NPCs with enhanced viability. In addition, when these NPCs are inducted to differentiate, they exhibit key characteristics of DA neurons. Thus, direct conversion of midbrain astrocytes is a possible cell therapy strategy to treat neurodegenerative diseases.

• 한국항공우주학회지
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• 제45권2호
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• pp.114-123
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• 2017

Little Intelligent Nanosatellite of KAIST(LINK)는 카이스트 항공우주 시스템 및 제어연구실(ASCL)에서 국제협력 프로젝트인 QB50의 일환으로 개발한 2U 크기의 큐브위성이다. QB50 프로젝트의 과학적 임무 목적은 열권 및 이온층 대기를 관측하는 것이며, 2017년 1분기부터 국제우주정거장에서 순차적으로 발사될 예정이다. 상기의 임무 구현을 위해 최종 비행모델을 개발하였으며, 수락 수준(Acceptance level)의 요구조건에 따라 환경시험 및 기능시험을 수행하여 위성의 성능 및 설계의 검증을 완료하였다. 본 논문에서는 비행모델 개발과 진동시험 및 열진공시험 결과에 대해 기술하였다.

• Biomolecules & Therapeutics
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• 제26권4호
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• pp.380-388
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• 2018

Neural stem cells (NSCs) have the ability to self-renew and differentiate into multiple nervous system cell types. During embryonic development, the concentrations of soluble biological molecules have a critical role in controlling cell proliferation, migration, differentiation and apoptosis. In an effort to find optimal culture conditions for the generation of desired cell types in vitro, we used a microfluidic chip-generated growth factor gradient system. In the current study, NSCs in the microfluidic device remained healthy during the entire period of cell culture, and proliferated and differentiated in response to the concentration gradient of growth factors (epithermal growth factor and basic fibroblast growth factor). We also showed that overexpression of ASCL1 in NSCs increased neuronal differentiation depending on the concentration gradient of growth factors generated in the microfluidic gradient chip. The microfluidic system allowed us to study concentration-dependent effects of growth factors within a single device, while a traditional system requires multiple independent cultures using fixed growth factor concentrations. Our study suggests that the microfluidic gradient-generating chip is a powerful tool for determining the optimal culture conditions.

• Genomics & Informatics
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• 제8권4호
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• pp.185-193
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• 2010

Histone deacetylation and demethylation are epigenetic mechanisms implicated in cancer. Studies regarding the role of modulation of gene expression utilizing the histone deacetylase inhibitor scriptaid and the demethylating agent 5-azacytidine in HL-60 leukemia cells have been limited. We studied the possibility of recovering epigenetically silenced genes by scriptaid and 5-azacytidine in human leukemia cells by DNA microarray analysis. The first group was leukemia cells that were cultured with 5-azacytidine. The second group was cultured with scriptaid. The other group was cultured with both agents. Two hundred seventy newly developed genes were expressed after the combination of 5-azacytidine and scriptaid. Twenty-nine genes were unchanged after the combination treatment of 5-azacytidine and scriptaid. Among the 270 genes, 13 genes were differed significantly from the control. HPGD, CPA3, CEACAM6, LOC653907, ETS1, RAB37, PMP22, FST, FOXC1, and CCL2 were up-regulated, and IGLL3, IGLL1, and ASS1 were down-regulated. Eleven genes associated with oncogenesis were found among the differentially expressed genes: ETS1, ASCL2, BTG2, BTG1, SLAMF6, CDKN2D, RRAS, RET, GIPC1, MAGEB, and RGL4. We report the results of our leukemia cell microarray profiles after epigenetic combination therapy with the hope that they are the starting point of selectively targeted epigenetic therapy.

• Molecules and Cells
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• 제40권12호
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• pp.945-953
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• 2017

We report the biological functions of a zebrafish homologue of RING-finger protein 152 (rnf152) during embryogenesis. rnf152 was initially identified as a brain-enriched E3 ligase involved in early embryogenesis of zebrafish. Expression of rnf152 was ubiquitous in the brain at 24 hpf but restricted to the eyes, midbrain-hindbrain boundary (MHB), and rhombomeres at 48 hpf. Knockdown of rnf152 in zebrafish embryos caused defects in the eyes, MHB, and rhombomeres (r1-7) at 24 hpf. These defects in rnf152-deficient embryos were analyzed by whole-mount in situ hybridization (WISH) using neuroD, deltaD, notch1a, and notch3 probes. NeuroD expression was abolished in the marginal zone, outer nuclear layer (ONL), inner nuclear layer (INL), and ganglion cell layer (GCL) of the eyes at 27 hpf. Furthermore, deltaD and notch1a expression was remarkably reduced in the ONL, INL, subpallium, tectum, cerebellum, and rhombomeres (r1-7) at 24 hpf, whereas notch3 expression was reduced in the tectum, cerebellum, and rhombomeres at 24 hpf. Finally, we confirmed that expression of Notch target genes, her4 and ascl1a, also decreased significantly in these areas at 24 hpf. Thus, we propose that Rnf152 is essential for development of the eyes, midbrain and hindbrain, and that Delta-Notch signaling is involved.

• Molecules and Cells
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• 제40권6호
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• pp.426-433
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• 2017

Ephrin-A5 has been implicated in the regulation of brain morphogenesis and axon pathfinding. In this study, we used bacterial homologous recombination to express a LacZ reporter in various ephrin-A5 BAC clones to identify elements that regulate ephrin-A5 gene expression during mesencephalon development. We found that there is mesencephalon-specific enhancer activity localized to a specific +25.0 kb to +30.5 kb genomic region in the first intron of ephrin-A5. Further comparative genomic analysis indicated that two evolutionary conserved regions, ECR1 and ECR2, were present within this 5.5 kb region. Deletion of ECR1 from the enhancer resulted in disrupted mesencephalon-specific enhancer activity in transgenic embryos. We also found a consensus binding site for basic helix-loop-helix (bHLH) transcription factors (TFs) in a highly conserved region at the 3'-end of ECR1. We further demonstrated that specific deletion of the bHLH TF binding site abrogated the mesencephalon-specific enhancer activity in transgenic embryos. Finally, both electrophoretic mobility shift assay and luciferase-based transactivation assay revealed that the transcription factor Ascl1 bound the bHLH consensus binding site in the mesencephalon-specific ephrin-A5 enhancer in vitro. Together, these results suggest that the bHLH TF binding site in ECR1 is involved in the positive regulation of ephrin-A5 gene expression during the development of the mesencephalon.