Ips cells

OTULIN-related autoinflammatory syndrome (ORAS), a severe autoinflammatory disease, is caused by biallelic pathogenic variants of OTULIN, a linear ubiquitin-specific deubiquitinating enzyme. Loss of OTULIN attenuates linear ubiquitination by inhibiting the linear ubiquitin chain assembly complex (LUBAC). Here, we report a patient who harbors two rare heterozygous variants of OTULIN (p.P152L and p.R306Q). We demonstrated accumulation of linear ubiquitin chains upon TNF stimulation and augmented TNF-induced cell death in mesenchymal stem cells differentiated from patient-derived iPS cells, which confirms that the patient has ORAS...

Endogenous tags have become invaluable tools to visualize and study native proteins in live cells. However, generating human cell lines carrying endogenous tags is difficult due to the low efficiency of homology-directed repair. Recently, an engineered split mNeonGreen protein was used to generate a large-scale endogenous tag library in HEK293 cells. Using split mNeonGreen for large-scale endogenous tagging in human iPSCs would open the door to studying protein function in healthy cells and across differentiated cell types...

BACKGROUND: Uterine corpus endometrial cancer (UCEC) exhibit heterogeneity in their DNA repair capacity, which can impact their response to radiotherapy. Our study aimed to identify potential DNA repair-related biomarkers for predicting radiation response in UCEC. METHODS: We conducted a thorough analysis of 497 UCEC samples obtained from TCGA database. Using LASSO-COX regression analysis, we constructed a radiosensitivity signature and subsequently divided patients into the radiosensitive (RS) and the radioresistant (RR) groups based on their radiosensitivity index...

Clear cell renal cell carcinoma (ccRCC) presents challenges in early diagnosis and effective treatment. In this study, we aimed to establish a prognostic model based on G2M checkpoint-related genes and identify associated clusters in ccRCC through clinical bioinformatic analysis and experimental validation. Utilizing a single-cell RNA dataset (GSE159115) and bulk-sequencing data from The Cancer Genome Atlas (TCGA) database, we analyzed the G2M checkpoint pathway in ccRCC. Differential expression analysis identified 45 genes associated with the G2M checkpoint, leading to the construction of a predictive model with four key genes (E2F2, GTSE1, RAD54L, and UBE2C)...

BACKGROUND: Lung cancer (LC) is a leading cause of cancer-associated mortality worldwide, with high incidence and mortality rates. Ly6/PLAUR domain containing 3 (LYPD3) is a tumorigenic and highly glycosylated cell surface protein that has been rarely reported in LC. This study aimed to explore the prognostic role and immune cell infiltration of LYPD3 in LC. METHODS: We used ExoCarta, a database of exosomal proteins and RNA, to select exosomes in LC. The Tumor Immune Estimation Resource (TIMER) and Human Protein Atlas (HPA) databases were utilized to compare the expression of LYPD3 in LC...

Bietti's crystalline dystrophy (BCD) is an autosomal recessive chorioretinal degeneration caused by mutations in the CYP4V2 gene. It is characterized by cholesterol accumulation and crystal-like deposits in the retinas. Hydroxypropyl-β-cyclodextrin (HP-β-CyD) exerts therapeutic effects against BCD by reducing lysosomal dysfunction and inhibiting cytotoxicity in induced pluripotent stem cell (iPSC)-RPE cells established from patient-derived iPS cells. However, the ocular retention of HP-β-CyD is low and needs to be improved...

Porcine epidemic diarrhea virus (PEDV) causes immensely large economic losses worldwide in the swine industry. PEDV attacks the intestine, disrupts intestinal epithelium morphology and barrier integrity, and results in profound diarrhea and high mortality. A commercially available isotonic protein solution (IPS) (Tonisity Px) has anecdotally been reported to be effective in supportive treatment of piglets with active PEDV infections. This study evaluated the effects of supplementing (or not) the drinking water of 14 day old PEDV-infected piglets with the IPS on the content of E-cadherin, fibronectin, interferon-alpha (IFN-α), and matrix metalloproteinase 9 (MMP-9) in duodenal tissue...

We successfully developed an induced pluripotent stem cell (iPSC) line, SYSUSHi001-A, from the peripheral blood mononuclear cells (PBMC) of a patient with Acute Myeloid Leukemia, harboring two genetic mutations (XPO1: c.591-4_591-3dupTT; PALB2: c.3296C > T; p.T1099M). This iPSC line was facilitated through the use of episomal plasmids encoding OCT4, SOX2, KLF4, L-MYC, and human miR-302. The SYSUSHi001-A iPSC line exhibited characteristic embryonic stem cell-like morphology, maintained the XPO1 and PALB2 mutations, expressed key pluripotency markers, preserved a normal karyotype (46, XY), and demonstrated the ability to differentiate into cells from all three germ layers in vitro...

Gastric cancer (GC) is the fifth most prevalent malignancy worldwide, characterized by poor prognosis. Apoptosis is interacted with hypoxia in tumorigenesis. This study attempted to delineate potential value of apoptosis and hypoxia-related genes (AHRGs) in prognosis of gastric cancer. Differential expression analysis was performed on GC transcriptomic data from TCGA. Apoptosis-related genes (ARGs) and hypoxia-related genes (HRGs) were obtained from MSigDB, followed by intersecting them with differentially expressed genes (DEGs) in GC...

The mammalian brain, especially the cerebral cortex, has evolved to increase in size and complexity. The proper development of the cerebral cortex requires the coordination of several events, such as differentiation and migration, that are essential for forming a precise six-layered structure. We have previously reported that Cdk5-mediated phosphorylation of JIP1 at T205 modulates axonal out-growth. However, the spatiotemporal expression patterns and functions of these three genes (Cdk5, Cdk5r1 or p35, and Mapk8ip1 or JIP1) in distinct cell types during cortical development remain unclear...

BACKGROUND: Immunotherapy has changed the treatment landscape for lung cancer. This study aims to construct a tumor mutation-related model that combines long non-coding RNA (lncRNA) expression levels and tumor mutation levels in tumor genomes to detect the possibilities of the lncRNA signature as an indicator for predicting the prognosis and response to immunotherapy in lung adenocarcinoma (LUAD). METHODS: We downloaded the tumor mutation profiles and RNA-seq expression database of LUAD from The Cancer Genome Atlas (TCGA)...

Cytosolic peptide:N-glycanase (NGLY1, PNGase) is an enzyme that cleaves N-glycans from misfolded glycoproteins. In 2012, a human genetic disorder, NGLY1 deficiency, was first reported to be caused by mutations of the NGLY1 gene. Since then, there has been rapid progresses on NGLY1 biology, and gene therapy has been proposed as a promising therapeutic option for NGLY1 deficiency. While a plasma/urine biomarker has also been developed for this disease, detection of NGLY1 activity could be another viable option for early diagnosis of NGLY1 deficiency...

Background: Previous studies have shown that cellular senescence is strongly associated with tumorigenesis and the tumor microenvironment. Accordingly, we developed a novel prognostic signature for intrahepatic cholangiocarcinoma (ICCA) based on senescence-associated long non-coding RNAs (SR-lncRNAs) and identified a lncRNA-miRNA-mRNA axis involving in ICCA. Methods: Based on the 197 senescence-associated genes (SRGs) from Genacards and their expression in Fu-ICCA cohort, we identified 20 lncRNAs as senescence-associated lncRNAs (SR-lncRNAs) through co-expression and cox-regression analysis...

A patient with the PSEN1 E280A mutation and homozygous for APOE3 Christchurch ( APOE3Ch ) displayed extreme resistance to Alzheimer's disease (AD) cognitive decline and tauopathy, despite having a high amyloid burden. To further investigate the differences in biological processes attributed to APOE3Ch , we generated induced pluripotent stem (iPS) cell-derived cerebral organoids from this resistant case and a non-protected control, using CRISPR/Cas9 gene editing to modulate APOE3Ch expression. In the APOE3Ch cerebral organoids, we observed a protective pattern from early tau phosphorylation...

The transcription factor GATA-1 is essential for erythroid differentiation. Recently, FAM210B, which encodes a mitochondrial inner membrane protein, has been identified as a novel target of GATA-1. To clarify the role of FAM210B, we depleted endogenous FAM210B in human iPS-derived erythroid progenitor (HiDEP-1) cells, and found that erythroid differentiation was more pronounced in the FAM210B depleted cells. Comprehensive metabolite analysis revealed a decline in mitochondrial function accompanied by increased lactate production, indicative of anaerobic glycolysis...

INTRODUCTION: Chimeric antigen receptor natural killer (CAR-NK) cells have been found to be successful in treating hematologic malignancies and present potential for usage in solid tumors. METHODS: In this study, we created CD276-targeted CAR-expressing NK cells from pluripotent stem cells (iPSC CD276-targeted CAR-NK cells) and evaluated their cytotoxicity against esophageal squamous cell carcinoma (ESCC) using patient-specific organoid (PSO) models comprising of both CD276-positive and CD276-negative adjacent epithelium PSO models (normal control PSO, NC PSO) as well as primary culture of ESCC cell models...

INTRODUCTION: The variable clinical course of chronic lymphocytic leukemia (CLL) and the lack of consensus on follow-up and treatment strategies have necessitated a prognostic model for identifying high-risk patients at the time of diagnosis. METHODS: We involved a retrospective analysis of demographic and clinical characteristics of 212 patients diagnosed with Binet stage A CLL and thus eligible for risk stratification by both the International Prognostic Score for Early-stage CLL (IPS-E) and the alternative IPS-E (AIPS-E)...

BACKGROUND AIMS: In the classical form of α1-antitrypsin deficiency a misfolded variant α1-antitrypsin Z accumulates in the endoplasmic reticulum of liver cells and causes liver cell injury by gain-of-function proteotoxicity in a sub-group of affected homozygotes but relatively little is known about putative modifiers. Here we carried out genomic sequencing in a uniquely affected family with an index case of liver failure and 2 homozygous siblings with minimal or no liver disease...

Cisplatin resistance plays a significant role in the dismal prognosis and progression of muscle-invasive bladder cancer (MIBC). However, the strategies to predict prognosis and cisplatin resistance are inefficient, and it remains unclear whether cisplatin resistance is associated with tumor immunity. In this study, we integrated the transcriptional data from cisplatin-resistant cell lines and a TCGA-MIBC cohort to establish cisplatin-resistance-related cluster classification and a cisplatin-resistance-related gene risk score (CRRGRS)...

Induced pluripotent stem cells (iPSCs) and their derivatives have been described to display epigenetic memory of their founder cells, as well as de novo reprogramming-associated alterations. In order to selectively explore changes due to the reprogramming process and not to heterologous somatic memory, we devised a circular reprogramming approach where somatic stem cells are used to generate iPSCs, which are subsequently re-differentiated into their original fate. As somatic founder cells, we employed human embryonic stem cell-derived neural stem cells (NSCs) and compared them to iPSC-derived NSCs derived thereof...