https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/294 2026-07-24T10:56:47Z https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/218426 Title: Functional expression of calcium homeostasis modulator 2 (CALHM2) regulates the bioenergetic transition of BV2 microglial cells Authors: Choi, Si Won; Kim, Jintae; Yu, Jinwon; Park, Kyoung Sun; Chung, Elina Da Sol; Kim, Gwanghun; Shin, Hyun Mu; Kim, Sung Joon Abstract: Microglia play pivotal roles in neuroinflammation and central nervous system disorders. The Calcium Homeostasis Modulator (CALHM) family forms large-pore ion channels implicated in ATP release and mitochondrial function. Here, we identified the functional expression of CALHM in BV2 microglial cells. Whole-cell patch-clamp recordings revealed a thermosensitive, voltage-gated slow outward current, consistent with the cloned CALHM channel current (ICALHM). RT-PCR confirmed that CALHM2 is the predominantly expressed isoform in BV2. CRISPR/Cas9-mediated knockout of Calhm2 (CALHM2−/−) abolished the ICALHM in BV2. While ATP release and Ca2+ influx rate was not affected, Seahorse XF analysis revealed an impaired metabolic flexibility in CALHM2−/−. Specifically, the LPS-induced increase in the oxygen consumption rate (OCR) was abolished, and the extracellular acidification rate (ECAR) was reduced in the LPS-treated CALHM2−/− cells. These results demonstrate that CALHM2 ​in microglia might be essential for the metabolic shift required during inflammatory activation. 2026-09-01T00:00:00Z https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/219053 Title: Dysregulation of astrocytic DNAJC6 contributes to sporadic Parkinson's disease pathogenesis Authors: Darsono, Wahyu Handoko Wibowo; Hwang, Yeongran; Valencia, Erica; Gunawan, Leonardo Tejo; Hyeon, Seung Jae; Ryu, Hoon; Stein, Thor D.; Chang, Mi-Yoon; Wulansari, Noviana; Lee, Sang-Hun Abstract: Loss-of-function mutations in DNAJC6, encoding the cochaperone auxilin (HSP40 family), cause familial juvenile-onset Parkinson's disease (PD). Given the chaperone role of DNAJC6 in cellular homeostasis in adult neurons, we hypothesized that DNAJC6 dysfunction may not be limited to juvenile-onset disorders but could also be associated with adult-onset brain diseases. Here, we show that DNAJC6 expression is significantly downregulated in postmortem substantia nigra tissues and transcriptomic datasets from patients with late-onset sporadic PD. Consistently, human pluripotent stem cell-derived midbrain cultures exhibited reduced DNAJC6 expression under multiple PD-associated conditions. Mechanistically, DNAJC6 loss resulted from impaired transcription mediated by the midbrain-specific factors NURR1/FOXA2 and reduced protein stability regulated by LRRK2. Beyond neurons, DNAJC6 was robustly expressed in astrocytes and similarly downregulated in sporadic PD contexts. Astrocytic DNAJC6 deficiency impaired phagocytic, autolysosomal, and mitochondrial functions while promoting a proinflammatory phenotype, thereby exacerbating neurodegenerative pathology. Importantly, epigenetic restoration of DNAJC6 in neurons and astrocytes using a CRISPRa-AAV9 system in the substantia nigra of an α-synuclein-induced PD mouse model alleviated behavioral deficits and neuropathology. These findings provide evidence that DNAJC6 dysregulation is associated with pathogenic processes in sporadic PD and suggest that targeting neuronal and astrocytic DNAJC6 could represent a potential disease-modifying strategy. 2026-06-01T00:00:00Z https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/211881 Title: Hippocalcin Regulates NMDA Receptor Function and Neuronal Activity Through Elavl3 in Mouse Hippocampal Neural Precursor Cells Authors: Kang, Min-Jeong; Jung, Sung Jun; Son, Hyeon; Han, Joong-Soo; Park, Shin-Young Abstract: Hippocalcin (HPCA), a neuron-enriched calcium-binding protein, plays a critical role in brain function, but its role in neural precursor cells remains unclear. N-methyl-D-aspartate (NMDA) receptors are calcium-permeable glutamate receptors essential for neurodevelopment and synaptic plasticity, and their function has been implicated in neurological conditions. In this study, we investigated the role of HPCA in regulating NMDA receptor expression and function in mouse hippocampal neural precursor cells (mHNPCs). HPCA knockdown significantly reduced the expression of NMDA receptor-related genes, including Grin2C, Shank1, Serpine2, and selectively attenuated NMDA-induced calcium signaling. Transcriptomic analysis identified ELAV-like RNA-binding protein 3 (Elavl3), a neuron-enriched factor associated with neuronal activity, as a downstream candidate affected by HPCA knockdown. Consistently, Elavl3 suppression phenocopied HPCA deficiency, resulting in impaired NMDA receptor activity and reduced neuronal differentiation. Furthermore, hippocampal HPCA knockdown in vivo led to alterations in locomotor activity, contextual memory, and affective behaviors. Taken together, these findings demonstrate that HPCA supports NMDA receptor function and neuronal development, in part through Elavl3-associated pathways, and highlight HPCA as an important regulator of hippocampal function. 2026-03-01T00:00:00Z https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/210812 Title: Single-cell RNA Sequencing–Based analysis of diverse ion-channel transcripts across human CD4+ T-cell subsets Authors: Lee, Ji-min; Kim, Jintae; Kim, Woo-kyung; Kim, Hyun-jong Abstract: CD4+ T lymphocytes orchestrate adaptive immunity and diversify into helper and regulatory subsets that are selectively implicated in autoimmune and allergic diseases. Although ion channels are key determinants of lymphocyte activation and homeostasis, their subset-resolved expression patterns in human CD4+ T cells remain incompletely defined. Here, naïve CD4+ T cells were isolated from human peripheral blood mononuclear cells, polarized in vitro into Th1, Th2, Th17, and regulatory T (Treg) cells, and profiled by single-cell RNA sequencing (scRNA-seq). Unsupervised clustering resolved naïve and differentiated states and enabled subset annotation by canonical marker panels. Comparative analysis of an ion-channel/transporter gene panel revealed subset-biased transcript signatures, including differential representation of Ca2+-handling modules and membrane transport genes. Notably, Th2 showed enriched expression of ITPR1, Treg displayed relatively higher STIM2/ORAI3, and Th17 exhibited prominent AQP3 expression, alongside broad detection of core store-operated Ca2+ entry (SOCE) components across subsets. Collectively, these data provide a single-cell transcriptomic resource that delineates ion-transport landscapes across human CD4+ T-cell subset states and nominates candidate ionic regulators for follow-up mechanistic studies. 2026-02-01T00:00:00Z