Resistin Regulates Inflammation and Insulin Resistance in Humans via the Endocannabinoid System.

Resistin plays an important role in the pathophysiology of obesity-mediated insulin resistance in mice. However, the biology of resistin in humans is quite different from that in rodents. Therefore, the association between resistin and insulin resistance remains unclear in humans.

The maintenance mechanism of hematopoietic stem cell dormancy: role for a subset of macrophages.

Hematopoiesis is regulated by crosstalk between long-term repopulating hematopoietic stem cells (LT-HSCs) and supporting niche cells in the bone marrow (BM). Here, we describe the role of KAI1, which is mainly expressed on LT-HSCs and rarely on other hematopoietic stem-progenitor cells (HSPCs), in nichemediated LT-HSC maintenance. KAI1 activates TGF-β1/Smad3 signal in LT-HSCs, leading to the induction of CDK inhibitors and inhibition of the cell cycle.

Strategy of Patient-Specific Therapeutics in Cardiovascular Disease Through Single-Cell RNA Sequencing.

Recently, single cell RNA sequencing (scRNA-seq) technology has enabled the discovery of novel or rare subtypes of cells and their characteristics. This technique has advanced unprecedented biomedical research by enabling the profiling and analysis of the transcriptomes of single cells at high resolution and throughput. Thus, scRNA-seq has contributed to recent advances in cardiovascular research by the generation of cell atlases of heart and blood vessels and the elucidation of mechanisms involved in cardiovascular development and diseases.

A subset of macrophages and monocytes in the mouse bone marrow express atypical chemokine receptor 1.

Duffy antigen receptor for chemokines (DARC)/CD234, also known as atypical chemokine receptor 1 (ACKR1), is a seven-transmembrane domain protein expressed on erythrocytes, vascular endothelium, and a subset of epithelial cells (Peiper et al., 1995). Previously, we reported that ACKR1 was expressed in bone marrow macrophages.

KAI1(CD82) is a key molecule to control angiogenesis and switch angiogenic milieu to quiescent state.

Background: Little is known about endogenous inhibitors of angiogenic growth factors. In this study, we identified a novel endogenous anti-angiogenic factor expressed in pericytes and clarified its underlying mechanism and clinical significance.

Methods: Herein, we found Kai1 knockout mice showed significantly enhanced angiogenesis.

Plant callus-derived shikimic acid regenerates human skin through converting human dermal fibroblasts into multipotent skin-derived precursor cells.

Background: The human skin-derived precursors (SKPs) are a good cell source for regeneration. However, the isolation of SKP from human skin is limited. To overcome this drawback, we hypothesized that the component of plant stem cells could convert human fibroblasts to SKPs.

HLA DR Genome Editing with TALENs in Human iPSCs Produced Immune-Tolerant Dendritic Cells.

Although human induced pluripotent stem cells (iPSCs) can serve as a universal cell source for regenerative medicine, the use of iPSCs in clinical applications is limited by prohibitive costs and prolonged generation time. Moreover, allogeneic iPSC transplantation requires preclusion of mismatches between the donor and recipient human leukocyte antigen (HLA). We, therefore, generated universally compatible immune nonresponsive human iPSCs by gene editing.

An antibody against L1 cell adhesion molecule inhibits cardiotoxicity by regulating persistent DNA damage.

Targeting the molecular pathways underlying the cardiotoxicity associated with thoracic irradiation and doxorubicin (Dox) could reduce the morbidity and mortality associated with these anticancer treatments. Here, we find that vascular endothelial cells (ECs) with persistent DNA damage induced by irradiation and Dox treatment exhibit a fibrotic phenotype (endothelial-mesenchymal transition, EndMT) correlating with the colocalization of L1CAM and persistent DNA damage foci. We demonstrate that treatment with the anti-L1CAM antibody Ab417 decreases L1CAM overexpression and nuclear translocation and persistent DNA damage foci.

The Key Role of DNA Methylation and Histone Acetylation in Epigenetics of Atherosclerosis.

Atherosclerosis, which is the most common chronic disease of the coronary artery, constitutes a vascular pathology induced by inflammation and plaque accumulation within arterial vessel walls. Both DNA methylation and histone modifications are epigenetic changes relevant for atherosclerosis. Recent studies have shown that the DNA methylation and histone modification systems are closely interrelated and mechanically dependent on each other.

Usefulness of the Hematopoietic Stem Cell Donor Pool as a Source of HLA-Homozygous Induced Pluripotent Stem Cells for Haplobanking: Combined Analysis of the Cord Blood Inventory and Bone Marrow Donor Registry.

Induced pluripotent stem cells (iPSCs) have opened up unprecedented opportunities for novel therapeutic options for precision medicine. Hematopoietic stem cell (HSC) donor pools with previously determined HLA types may be ideal sources for iPSC production. Based on the HLA distribution of cryopreserved cord blood units (CBUs) and registered bone marrow (BM) donors, we estimated how much of the Korean population could be covered by HLA-homozygous iPSCs.

Transplantation of a 3D-printed tracheal graft combined with iPS cell-derived MSCs and chondrocytes.

For successful tracheal reconstruction, tissue-engineered artificial trachea should meet several requirements, such as biocompatible constructs comparable to natural trachea, coverage with ciliated respiratory mucosa, and adequate cartilage remodeling to support a cylindrical structure. Here, we designed an artificial trachea with mechanical properties similar to the native trachea that can enhance the regeneration of tracheal mucosa and cartilage through the optimal combination of a two-layered tubular scaffold and human induced pluripotent stem cell (iPSC)-derived cells. The framework of the artificial trachea was fabricated with electrospun polycaprolactone (PCL) nanofibers (inner) and 3D-printed PCL microfibers (outer).

NFATc1+CD31+CD45- circulating multipotent stem cells derived from human endocardium and their therapeutic potential.

Many studies have shown the existence of cardiac stem cells in the myocardium and epicardial progenitor cells in the epicardium. However, the characteristics of stem cells in the endocardium has not been fully elucidated. In this study, we investigated the origin of newly identified cells in the blood and their therapeutic potential.

Cyclase-associated protein 1 is a binding partner of proprotein convertase subtilisin/kexin type-9 and is required for the degradation of low-density lipoprotein receptors by proprotein convertase subtilisin/kexin type-9.

Aims: Proprotein convertase subtilisin/kexin type-9 (PCSK9), a molecular determinant of low-density lipoprotein (LDL) receptor (LDLR) fate, has emerged as a promising therapeutic target for atherosclerotic cardiovascular diseases. However, the precise mechanism by which PCSK9 regulates the internalization and lysosomal degradation of LDLR is unknown. Recently, we identified adenylyl cyclase-associated protein 1 (CAP1) as a receptor for human resistin whose globular C-terminus is structurally similar to the C-terminal cysteine-rich domain (CRD) of PCSK9.

Cell signaling and biological pathway in cardiovascular diseases.

Currently, coronary artery disease accounts for a large proportion of deaths occurring worldwide. Damage to the heart muscle over a short period of time leads to myocardial infarction (MI). The biological mechanisms of atherosclerosis, one of the causes of MI, have been well studied.

Efficient in vivo direct conversion of fibroblasts into cardiomyocytes using a nanoparticle-based gene carrier.

The reprogramming of induced cardiomyocytes (iCMs) has shown potential in regenerative medicine. However, in vivo reprogramming of iCMs is significantly inefficient, and novel gene delivery systems are required to more efficiently and safely induce in vivo reprogramming of iCMs for therapeutic applications in heart injury. In this study, we show that cationic gold nanoparticles (AuNPs) loaded with Gata4, Mef2c, and Tbx5 function as nanocarriers for cardiac reprogramming.

Imprinted gene Zinc finger protein 127 is a novel regulator of master pluripotency transcription factor, Oct4.

Induced pluripotent stem cells (iPSCs) show great promise for replacing current stem cell therapies in the field of regenerative medicine. However, the original method for cellular reprogramming, involving four exogenous transcription factors, is characterized by low efficiency. Here, we focused on using epigenetic modifications to enhance the reprogramming efficiency.

Gata6 in pluripotent stem cells enhance the potential to differentiate into cardiomyocytes.

Pluripotent stem cell (PSC) variations can cause significant differences in the efficiency of cardiac differentiation. This process is unpredictable, as there is not an adequate indicator at the undifferentiated stage of the PSCs. We compared global gene expression profiles of two PSCs showing significant differences in cardiac differentiation potential.

Protein-Induced Pluripotent Stem Cells Ameliorate Cognitive Dysfunction and Reduce Aβ Deposition in a Mouse Model of Alzheimer's Disease.

Transplantation of stem cells into the brain attenuates functional deficits in the central nervous system via cell replacement, the release of specific neurotransmitters, and the production of neurotrophic factors. To identify patient-specific and safe stem cells for treating Alzheimer's disease (AD), we generated induced pluripotent stem cells (iPSCs) derived from mouse skin fibroblasts by treating protein extracts of embryonic stem cells. These reprogrammed cells were pluripotent but nontumorigenic.

Identification of the early and late responder genes during the generation of induced pluripotent stem cells from mouse fibroblasts.

Background: The generation of induced pluripotent stem cell (iPSC), a substitute for embryonic stem cell (ESC), requires the proper orchestration of a transcription program at the chromatin level. Our recent approach for the induction of pluripotent stem cells from fibroblasts using protein extracts from mouse ESCs could overcome the potential tumorigenicity risks associated with random retroviral integration. Here, we examine the epigenetic modifications and the transcriptome of two types of iPSC and of partially reprogrammed iPSCs (iPSCp) generated independently from adult cardiac and skin fibroblasts to assess any perturbations of the transcription program during reprogramming.

Activation of Protein Kinase G (PKG) Reduces Neointimal Hyperplasia, Inhibits Platelet Aggregation, and Facilitates Re-endothelialization.

In spite of its great success in reducing restenosis, drug-eluting stent (DES) has unfavorable aspects such as stent thrombosis and delayed re-endothelialization. We examined the effects of PKG activation by Exisulind on neointimal formation, platelet aggregation, and re-endothelialization. Exisulind significantly reduced VSMCs viability, cell cycle progression, migration, and neointimal hyperplasia after vascular injury in rat carotid arteries.

E-Ras improves the efficiency of reprogramming by facilitating cell cycle progression through JNK-Sp1 pathway.

We have previously shown that pluripotent stem cells can be induced from adult somatic cells which were exposed to protein extracts isolated from mouse embryonic stem cells (mESC). Interestingly, generation of induced pluripotent stem (iPS) cells depended on the background of ES cell lines; possible by extracts from C57, but not from E14. Proteomic analysis of two different mES cell lines (C57 and E14) shows that embryonic Ras (E-Ras) is expressed differently in two mES cell lines; high level of E-Ras only in C57 mESC whose extracts allows iPS cells production from somatic cells.

Role of Zscan4 in secondary murine iPSC derivation mediated by protein extracts of ESC or iPSC.

Previously, we found that the delivery of mouse ES (mES) cell-derived proteins to adult fibroblasts enables the full reprogramming of these cells, converting them to mouse pluripotent stem cells (protein-iPS cells) without transduction of defined factors. During reprogramming, global gene expression and epigenetic status such as DNA methylation and histone modifications convert from somatic to ES-equivalent status. mES cell extract-derived iPS cells are biologically and functionally indistinguishable from mES cells in its potential in differentiation both in vitro and in vivo.