https://scholar.dgist.ac.kr/handle/20.500.11750/16865 2026-04-16T16:34:56Z https://scholar.dgist.ac.kr/handle/20.500.11750/57301 Title: Dipeptidyl peptidase 4 as an injury-responsive protein in the mouse sciatic nerve Author(s): Oh, Yeonsoo; Cho, Yongcheol Abstract: Dipeptidyl peptidase 4 (DPP4) is a membrane-bound protease known for its roles in immunity and metabolism; however, its function in the nervous system remains largely unexplored. We found that DPP4 is predominantly expressed in the Schwann cells of the sciatic nerve, and its systemic depletion in postnatal mice resulted in a decline in motor function. Importantly, the inhibition of its proteolytic activity did not affect axon regeneration, indicating that DPP4′s protease activity may not be directly involved in axon regeneration. Instead, we observed a reduction in DPP4 protein levels in the sciatic nerve after injury and increased in serum postinjury, suggesting that DPP4 may be shed into circulation, potentially mediating systemic responses following injury. These findings highlight DPP4′s importance in sensory function and its potential role in systemic responses after peripheral nerve injury. © 2024 The Author(s) 2024-11-30T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/47691 Title: βPix Guanine Nucleotide Exchange Factor Regulates Regeneration of Injured Peripheral Axons Author(s): Jeon, Yewon; Shin, Yoon Kyung; Kim, Hwigyeong; Choi, Yun Young; Kang, Minjae; Kwon, Younghee; Cho, Yongcheol; Chi, Sung Wook; Shin, Jung Eun Abstract: Axon regeneration is essential for successful recovery after peripheral nerve injury. Although growth cone reformation and axonal extension are crucial steps in axonal regeneration, the regulatory mechanisms underlying these dynamic processes are poorly understood. Here, we identify βPix (Arhgef7), the guanine nucleotide exchange factor for Rac1 GTPase, as a regulator of axonal regeneration. After sciatic nerve injury in mice, the expression levels of βPix increase significantly in nerve segments containing regenerating axons. In regrowing axons, βPix is localized in the peripheral domain of the growth cone. Using βPix neuronal isoform knockout (NIKO) mice in which the neuronal isoforms of βPix are specifically removed, we demonstrate that βPix promotes neurite outgrowth in cultured dorsal root ganglion neurons and in vivo axon regeneration after sciatic nerve crush injury. Activation of cJun and STAT3 in the cell bodies is not affected in βPix NIKO mice, supporting the local action of βPix in regenerating axons. Finally, inhibiting Src, a kinase previously identified as an activator of the βPix neuronal isoform, causes axon outgrowth defects in vitro, like those found in the βPix NIKO neurons. Altogether, these data indicate that βPix plays an important role in axonal regrowth during peripheral nerve regeneration. © 2023 by the authors. 2023-08-31T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/47656 Title: Precise base editing without unintended indels in human cells and mouse primary myoblasts Author(s): Yoon, Da Eun; Kim, Na-Rae; Park, Soo-Ji; Jeong, Tae Yeong; Eun, Bokkee; Cho, Yongcheol; Lim, Soo-Yeon; Lee, Hyunji; Seong, Je Kyoung; Kim, Kyoungmi Abstract: Base editors are powerful tools for making precise single-nucleotide changes in the genome. However, they can lead to unintended insertions and deletions at the target sites, which is a significant limitation for clinical applications. In this study, we aimed to eliminate unwanted indels at the target sites caused by various evolved base editors. Accordingly, we applied dead Cas9 instead of nickase Cas9 in the base editors to induce accurate substitutions without indels. Additionally, we tested the use of chromatin-modulating peptides in the base editors to improve nucleotide conversion efficiency. We found that using both dead Cas9 and chromatin-modulating peptides in base editing improved the nucleotide substitution efficiency without unintended indel mutations at the desired target sites in human cell lines and mouse primary myoblasts. Furthermore, the proposed scheme had fewer off-target effects than conventional base editors at the DNA level. These results indicate that the suggested approach is promising for the development of more accurate and safer base editing techniques for use in clinical applications. © 2023, The Author(s). 2023-11-30T15:00:00Z