Biology subjects

Kim, H.-K.

Publications and source records attributed to Kim, H.-K..

4 recordsLinked to original sources

bioRxiv2026

Human iPSCs and iPSC-Derived Endothelial Cells from PAD Patients and Healthy Donors Exhibit Comparable Characteristics and Potency: Implications for Autologous Cell Therapy in Peripheral Artery Disease

BACKGROUND: Peripheral artery disease (PAD) can lead to amputation in advanced cases, making cell therapy using human induced pluripotent stem cells (hiPSCs) a promising therapeutic option. hiPSC-derived endothelial cells (hiPSC-ECs) have shown favorable effects in treating experimental ischemic cardiovascular disease. An autologous approach for PAD patients is preferable to avoid immunological reactions. However, it is yet unknown whether hiPSCs and hiPSC-ECs derived from PAD patients have similar characteristics and potency compared to those derived from non-PAD donors. Therefore, we explored whether there are significant differences in the characteristics and potency of hiPSCs and hiPSC-ECs between non-PAD donors and PAD patients. METHODS: We generated hiPSCs from the blood of non-PAD donors and patients with PAD. We determined the pluripotency of hiPSCs using qRT-PCR, flow cytometry, immunostaining, RNA-seq, and teratoma formation assay. The genetic stability of hiPSCs was confirmed by G-banding karyotyping. We then differentiated hiPSCs into endothelial cells (ECs) in a clinically compatible manner. We compared the characteristics and therapeutic potency of hiPSC-ECs derived from non-PAD and PAD groups using qRT-PCR, flow cytometry, immunostaining, and RNA-seq. In vitro endothelial functions were determined by nitric oxide (NO) production and capillary network formation. Therapeutic potency and incorporation of engrafted hiPSC-ECs were evaluated in a hindlimb ischemia model. RESULTS: We successfully generated hiPSCs from the blood of seven non-PAD donors and eight PAD patients. Both non-PAD and PAD-derived hiPSCs exhibited similar expression levels of pluripotency markers. All hiPSCs, regardless of the group, formed teratomas and showed normal karyotypes. RNA-seq analyses revealed similar gene expression profiles between the groups. hiPSC-ECs derived from both non-PAD and PAD donors exhibited similar expression levels of EC markers at both the gene and protein levels. RNA-seq analyses showed no significant overall differences in gene expression profiles between the groups. Functional analyses demonstrated similar endothelial characteristics and function in hiPSC-ECs from both groups. Both groups showed similar perfusion recovery, limb salvage, and vessel-forming capacity. Engrafted hiPSC-ECs from both groups also exhibited similar angiogenic and vessel-forming capabilities. CONCLUSIONS: Our study demonstrated no significant differences in hiPSCs and hiPSC-ECs derived from non-PAD donors and PAD patients in terms of molecular and cell biological characteristics, therapeutic effects, and vessel-forming capability. Our study indicates that hiPSCs and hiPSC-ECs derived from PAD patients can serve as a novel platform for autologous cell therapy.

cell biology↗

bioRxiv2024

HP1a promotes chromatin liquidity and drives spontaneous heterochromatin compartmentalization

Compartmentalization of the nucleus into heterochromatin and euchromatin is highly conserved across eukaryotes. Constitutive heterochromatin (C-Het) constitutes a liquid-like condensate that packages the repetitive regions of the genome through the enrichment of histone modification H3K9me3 and recruitment of its cognate reader protein Heterochromatin Protein-1 (HP1a). The ability for well-ordered nucleosome arrays and HP1a to independently form biomolecular condensates suggests that the emergent material properties of C-Het compartments may contribute to its functions such as force-buffering, dosage-dependent gene silencing, and selective permeability. Using an in vitro reconstitution system we directly assess the contributions of H3K9me3 and HP1a on the biophysical properties of C-Het. In the presence of HP1a, H3K9me3 (Me-) and unmodified (U-) chromatin form co-condensates composed of distinct, immiscible domains. These chromatin domains form spontaneously and are reversible. Independently of HP1a, H3K9me3 modifications are sufficient to increase linker-DNA length within chromatin arrays and slow chromatin condensate growth. HP1a increases the liquidity of chromatin condensates while dramatically differentiating the viscoelastic properties of Me-chromatin versus U-chromatin. Mutating key residues in HP1a show that HP1a interactions with itself and chromatin determine the relative interfacial tension between chromatin compartments, however the formation of condensates is driven by the underlying chromatin. These direct measurements map the energetic landscape that determines C-Het compartmentalization, demonstrating that nuclear compartmentalization is a spontaneous and energetically favorable process in which HP1a plays a critical role in establishing a hierarchy of affinities between H3K9me3-chromatin and unmodified-chromatin. Highlights HP1a is necessary and sufficient for heterochromatin compartmentalization. Heterochromatin compartmentalization is reversible and proceeds through microphase-separation. H3K9me3 is sufficient to change nucleosome-array dynamics and mesoscale material properties. HP1a increases chromatin liquidity. HP1a-chromatin interaction modes tune the interfacial tensions and morphologies of heterochromatin compartments.

biophysics↗

bioRxiv2024

Shift from visceral to subcutaneous fat in Cyp17a1 knockout rats prevent the progression of metabolic syndrome

In this study, we investigated the effects of Cyp17a1 gene knockout (KO) on obesity and metabolic syndrome. Cyp17a1 KO in rats using CRISPR-Cas9 resulted in sex dimorphism and obesity, and interestingly, idiopathic accumulation was found in subcutaneous adipose tissue. Surprisingly, an insulin tolerance test and oral glucose tolerance test did not show any issues with insulin sensitivity and secretion despite hyperglycemia. In addition, Cyp17a1 KO rats showed normal plasma insulin and free fatty acid levels compared to wild-type rats, and blood biochemistry analysis revealed normal triglyceride, total cholesterol, high-density lipoprotein, and low-density lipoprotein levels. Cyp17a1 KO adipose-tissue-derived stem cells from subcutaneous fat showed increased expression of KLF5, an early adipogenesis marker, which implies enhanced adipogenic potential in subcutaneous adipose tissue. When gene expression associated with lipid, glucose, and insulin metabolism as well as inflammation in adipose tissue was examined, a metabolic shift to subcutaneous adipose tissue was discovered in the Cyp17a1 KO group. In conclusion, in the Cyp17a1 KO rat models we generated for the first time, the phenotype promoted by obesity reflected health obesity hypothesis, but this did not result in metabolic syndrome due to enhanced metabolism in the subcutaneous fats.

physiology↗

bioRxiv2020

Differential risk of incident cancer in patients with heart failure: A nationwide population-based cohort study

BackgroundHeart failure (HF) and cancer are currently two leading causes of mortality, and sometimes coexist. However, the relationship between them is not completely elucidated. We aimed to investigate whether patients with HF are predisposed to cancer development using the large Korean National Health Insurance claims database. Methods and findingsThis study included 128,441 HF patients without a history of cancer and 642,205 age- and sex-matched individuals with no history of cancer and HF between 1 January 2010 and 31 December 2015. During a median follow-up of 4.06 years, 11,808 patients from the HF group and 40,805 participants from the control were newly diagnosed with cancer (cumulative incidence, 9.2% vs. 6.4%, p<0.0001). Patients with HF presented a higher risk for cancer development compared to controls in multivariable Cox analysis (hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.61 - 1.68). The increased risk was consistent for all site-specific cancers. To minimize potential surveillance bias, additional analysis was performed by eliminating participants who developed cancer within the initial 2 years of HF diagnosis (i.e. 2-year lag analysis). In the 2-year lag analysis, the higher risk of overall cancer remained significant in patients with HF (HR 1.09, 95% CI 1.05 - 1.13), although the association was weaker. Among the site-specific cancers, three types of cancer (lung, liver/biliary/pancreas, and hematologic malignancy) were consistently at higher risk in patients with HF. ConclusionsCancer incidence is higher in patients with HF than in the general population. Active surveillance of coexisting malignancy needs to be considered in these patients.

cancer biology↗