Publications by authors named "Sang-Je Park"

Cynomolgus monkey iPSCs were generated from ear fibroblasts, offering a non-invasive and accessible cell source for autologous therapies and preclinical research. These iPSCs demonstrated robust pluripotency and differentiation potential, successfully giving rise to functional macrophages. Validation confirmed chromosomal stability, transgene clearance, and mycoplasma-free status.

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  • Aging research is still largely unexplored, prompting an investigation into the immune response characteristics of healthy male cynomolgus macaques across different age groups.* -
  • The study identified three distinct aging patterns in gene expression related to immune responses: increased expression linked to innate immunity causing chronic inflammation, and decreased expression linked to adaptive immunity affecting antibody diversity.* -
  • Findings suggest that the gene expression patterns in macaques reflect aging processes and correlate with human disease states, potentially aiding in future predictions of human health issues.*
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The CRISPR-Cas nickase system for genome editing has attracted considerable attention owing to its safety, efficiency, and versatility. Although alternative effectors to Cas9 have the potential to expand the scope of genome editing, their application has not been optimized. Herein, we used an enhanced CRISPR-Cas12a nickase system to induce mutations by targeting genes in a human-derived cell line.

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Transposable elements (TEs) are mobile DNA entities that can move within the host genome. Over long periods of evolutionary time, TEs are typically silenced via the accumulation of mutations in the genome, ultimately resulting in their immobilization. However, they still play an important role in the host genome by acting as regulatory elements.

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Cynomolgus monkeys, due to their close anatomical, genetic and physiological similarity to humans, have been employed as a popular laboratory non-human primate model over rodents. Primate animal induced pluripotent stem cell (iPSC) have been used to aid on the investigation of autologous regenerative therapies. Here, we reprogrammed cynomolgus monkey ear skin fibroblasts (cmESFs) into iPSCs as a starting material for autologous based study.

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Cynomolgus monkeys, a non-human primate species, are genetically and physiologically similar to humans; hence, they have been employed as an ideal developmental and biomedical model. Non-human primate animals and their induced pluripotent stem cell (iPSC) derivatives have been used as a research tool to investigate autologous regenerative medicine. Here, we reprogrammed cynomolgus monkey kidney fibroblasts (cmKFs) as a control for animal iPSCs and to study autologous transplant.

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  • MicroRNAs (miRNAs), like hsa-miR-422a (derived from SINE), play a key role in regulating gene expression at the post-transcriptional level by targeting complementary mRNA sequences.
  • The study identified AT-Rich Interaction Domain 5 B as a target gene for hsa-miR-422a and used a dual luciferase assay in HepG2 cells to confirm the miRNA's impact on gene expression.
  • Results showed that hsa-miR-422a enhances gene expression by interacting with transcription factors, particularly NF-E2, indicating its role as a super enhancer miRNA.
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Background: Obesity due to an excessive intake of nutrient disturbs the hypothalamus-mediated energy metabolism subsequently develops metabolic disorders. In this study, we investigated the effect of pine needle extract (PNE) on the hypothalamic proopiomelanocortin (POMC) neurons involved in the regulation of energy balance via melanocortin system and fat tissue metabolism.

Methods: We performed electrophysiological and immunohistochemical analyses to determine the effect of PNE on POMC neurons.

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  • * The study focused on cynomolgus monkey genes, identifying ten genes with AluYRa1 at their 3' end, predominantly in a sense orientation, suggesting a connection to polyadenylation processes.
  • * RNA-seq data from 30 monkeys revealed that around 74% of potential polyadenylation sites were linked to sense-oriented AluYRa1, indicating its significant role in diversifying gene transcripts.
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  • * The expression levels of hsa-miRNA-625-5p vary across different species, prompting the design of primers to study its binding sites on the GATAD2B gene's 3'UTR.
  • * A luciferase assay tested the interaction between hsa-miRNA-625 and GATAD2B, revealing that the number and location of binding sites can influence gene expression, with NF-κB enhancing the activity of hsa-miRNA
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  • African green monkeys (AGMs) serve as models in biomedical research to study aging and age-related diseases through advanced next-generation sequencing.
  • Researchers analyzed the blood transcriptomes of nine healthy aged AGMs over two years, discovering a significant increase in differentially expressed genes (DEGs) associated with aging.
  • A majority of these DEGs were related to processes like translation and rRNA metabolism, leading to the identification of 29 candidate aging genes that could be potential targets for future aging treatments.
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microRNAs (miRNAs) are non-coding RNA molecules involved in the regulation of gene expression. miRNAs inhibit gene expression by binding to the 3' untranslated region (UTR) of their target gene. miRNAs can originate from transposable elements (TEs), which comprise approximately half of the eukaryotic genome and one type of TE, called the long terminal repeat (LTR) is found in class of retrotransposons.

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Background: Alternative splicing (AS) generates various transcripts from a single gene and thus plays a significant role in transcriptomic diversity and proteomic complexity. Alu elements are primate-specific transposable elements (TEs) and can provide a donor or acceptor site for AS. In a study on TE-mediated AS, we recently identified a novel AluSz6-exonized ACTR8 transcript of the crab-eating monkey (Macaca fascicularis).

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Nonhuman primate models are valuable in biomedical research. However, reference data for clinical pathology parameters in cynomolgus and rhesus monkeys are limited. In the present study, we established hematologic and biochemical reference intervals for healthy cynomolgus and rhesus monkeys anesthetized with ketamine hydrochloride.

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  • The study explores how interactions between the nervous system and immune system contribute to the development of Parkinson's disease (PD) and potential treatment options.
  • Research with non-human primates revealed chronic infiltration of T lymphocytes in the brain and changes in microglial activation after exposure to a specific neurotoxin (MPTP), which mimics PD.
  • Findings highlight the role of CD4+ and CD8+ T lymphocytes in neuron loss and suggest that understanding these immune responses could lead to better prevention and therapy for PD.
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Background: The BLOC1S2 gene encodes the multifunctional protein BLOS2, a shared subunit of two lysosomal trafficking complexes: i) biogenesis of lysosome-related organelles complex-1 and i) BLOC-1-related complex. In our previous study, we identified an intriguing unreported transcript of the BLOC1S2 gene that has a novel exon derived from two transposable elements (TEs), MIR and AluSp. To investigate the evolutionary footprint and molecular mechanism of action of this transcript, we performed PCR and RT-PCR experiments and sequencing analyses using genomic DNA and RNA samples from humans and various non-human primates.

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X-box binding protein 1 (XBP1) mRNA processing plays a crucial role in the unfolded protein response (UPR), which is activated in response to endoplasmic reticulum (ER) stress. Upon accumulation of the UPR-converted XBP1 mRNA splicing from an unspliced (u) XBP1 (inactive) isoform to the spliced (s) XBP1 (active) isoform, inositol-requiring enzyme 1 α (IRE1α) removes a 26-nucleotide intron from uXBP1 mRNA. Recent studies have reported the assessment of ER stress by examining the ratio of sXBP1 to uXBP1 mRNA (s/uXBP1 ratio) via densitometric analysis of PCR bands relative to increased levels of sXBP1 to uXBP1 using a housekeeping gene for normalization.

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Mitochondria continuously fuse and divide to maintain homeostasis. An impairment in the balance between the fusion and fission processes can trigger mitochondrial dysfunction. Accumulating evidence suggests that mitochondrial dysfunction is related to neurodegenerative diseases such as Parkinson's disease (PD), with excessive mitochondrial fission in dopaminergic neurons being one of the pathological mechanisms of PD.

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Microorganisms play important roles in obesity; however, the role of the gut microbiomes in obesity is controversial because of the inconsistent findings. This study investigated the gut microbiome communities in obese and lean groups of captive healthy cynomolgus monkeys reared under strict identical environmental conditions, including their diet. No significant differences in the relative abundance of , and were observed between the obese and lean groups, but a significant difference in ( < 0.

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Background: The guidelines for applying individual adjustments to macaques according to the severity of behavioral symptoms during 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment were provided to reproduce stable chronic Parkinsonism in a recent study (Potts et al., 2014). But, since there are insufficient guidelines regarding objective severity criteria of individual symptoms for adjustments of MPTP treatment, it is difficult to develop MPTP-induced chronic non-human primate (NHP) models with stable symptoms.

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Background: The characterization of genomic or epigenomic variation in human and animal models could provide important insight into pathophysiological mechanisms of various diseases, and lead to new developments in disease diagnosis and clinical intervention. The African green monkey (AGM; Chlorocebus aethiops) and cynomolgus monkey (CM; Macaca fascicularis) have long been considered important animal models in biomedical research. However, non-human primate-specific methods applicable to epigenomic analyses in AGM and CM are lacking.

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Tyrosinase is a copper-containing enzyme that regulates melanin biosynthesis and is encoded by the tyrosinase (TYR) gene. Previous studies demonstrated that mutations in TYR could lead to oculocutaneous albinism type 1 (OCA1) owing to the failure of melanin formation. Although a previous study found that albinism in the rhesus monkey was derived from a mutation in TYR, the identification and characterization of this gene in non-human primates has not been achieved thus far.

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Cathepsin F, which is encoded by , is a cysteine proteinase ubiquitously expressed in several tissues. In a previous study, novel transcripts of the gene were identified in the crab-eating monkey deriving from the integration of an element-YRa1. The occurrence of YRa1-derived alternative transcripts and the mechanism of exonization events in the gene of human, rhesus monkey, and crab-eating monkey were investigated using PCR and reverse transcription PCR on the genomic DNA and cDNA isolated from several tissues.

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encodes a subunit of the tRNA-splicing endonuclease complex, which catalyzes the identification and cleavage of introns from precursor tRNAs. Previously, we identified an -derived alternative transcript in of cynomolgus monkey. Reverse transcription-polymerase chain reaction (RT-PCR) amplification and sequence analysis of primate and human samples identified five novel alternative transcripts, including the exonized transcript.

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ZKSCAN5 (also known as ZFP95) is a zinc-finger protein belonging to the Krűppel family. ZKSCAN5 contains a SCAN box and a KRAB A domain and is proposed to play a distinct role during spermatogenesis. In humans, alternatively spliced ZKSCAN5 transcripts with different 5'-untranslated regions (UTRs) have been identified.

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