Biology subjects

KIM, J.-I.

Publications and source records attributed to KIM, J.-I..

3 recordsLinked to original sources

bioRxiv2026

Retrosplenial cortex vulnerability links severe hypoglycemia to cognitive impairment through neuron-microglia crosstalk

Severe hypoglycemia remains a serious adverse effect of insulin therapy in individuals with diabetes and is linked to cognitive decline, yet the mechanisms by which transient metabolic stress leads to persistent neuronal dysfunction remain poorly defined. Using mouse models of acute severe hypoglycemia and integrated screening, we identified the retrosplenial cortex as a previously unrecognized brain region that is particularly vulnerable to hypoglycemia-induced neuronal damage. This injury is driven by a feedforward interaction between neuron-specific Drp1-dependent mitochondrial fission and microglial IL-1 signaling, as pharmacological or genetic targeting of either pathway suppressed the other, rescued neuronal damage, and reversed cognitive impairment. These findings identify a region-specific neuron-microglia injury circuit that links severe hypoglycemia to cognitive dysfunction and suggest a therapeutic strategy to protect brain function without compromising diabetes management.

neuroscience↗

bioRxiv2023

Micro-Scale Control of Oligodendrocyte Morphology and Myelination by the Intellectual Disability-Linked Protein Acyltransferase ZDHHC9

Mutations in the X-linked ZDHHC9 gene cause cognitive deficits in humans, with a subset of patients suffering from epilepsy. X-linked intellectual disability (XLID) is often ascribed to neuronal deficits, but here we report that expression of human and mouse ZDHHC9 orthologs is far higher in myelinating oligodendrocytes (OLs) than in other CNS cell types. ZDHHC9 codes for a protein acyltransferase (PAT), and we found that ZDHHC9 is the most highly expressed PAT in OLs. Wild type ZDHHC9 localizes to Golgi outposts in OL processes, but other PATs and XLID mutant forms of ZDHHC9 are restricted to OL cell bodies. Using genetic tools for OL progenitor fate tracing and sparse cell labeling, we show that mice lacking Zdhhc9 have grossly normal OL development but display extensive morphological and structural myelin abnormalities. Consistent with the hypothesis that these deficits are OL-autonomous, they are broadly phenocopied by acute Zdhhc9 knockdown in cultured conditions. Finally, we found that ZDHHC9 palmitoylates Myelin Basic Protein (MBP) in heterologous cells, and that palmitoylation of MBP is impaired in the Zdhhc9 knockout brain. Our findings provide critical insights into the mechanisms of ZDHHC9-associated XLID and shed new light on the palmitoylation-dependent control of myelination.

neuroscience↗

bioRxiv2020

Engineered Prime Editors with PAM flexibility

Although prime editors are a powerful tool for genome editing, which can generate various types of mutations such as nucleotide substitutions, insertions, and deletions in the genome without double-strand breaks or donor DNA, the conventional prime editors are still limited to its target scopes because of the PAM preference of the spCas9 protein. Here, we described the engineered prime editors to expand the range of their target sites using various PAM-flexible Cas9 variants.

bioengineering↗