hesc

The DNAJC19 gene, a member of DNAJ heat shock protein (Hsp40) family, is localized within the inner mitochondrial membrane (IMM) and plays a crucial role in regulating the function and localization of mitochondrial Hsp70 (MtHsp70). Mutations in the DNAJC19 gene cause Dilated Cardiomyopathy with Ataxia Syndrome (DCMA). The precise mechanisms underlying the DCMA phenotype caused by DNAJC19 mutations remain poorly understood, and effective treatment modalities were lacking unitl recently. By using CRISPR-Cas9 gene editing technology, this study generated a DNAJC19-knockout (DNAJC19-KO) human embryonic stem cell line (hESC), which will be a useful tool in studying the pathogenesis of DCMA...

Per- and polyfluoroalkyl substances (PFAS) are extensively utilized in varieties of products and tend to accumulate in the human body including umbilical cord blood and embryos/fetuses. In this study, we conducted an assessment and comparison of the potential early developmental toxicity of perfluorooctanoic acid (PFOA), undecafluorohexanoic acid (PFHxA), heptafluorobutyric acid, perfluorooctanesulfonate (PFOS), perfluorohexanesulfonate, and perfluorobutyric acid at noncytotoxic concentrations relevant to human exposure using models based on human embryonic stem cells in both three-dimensional embryoid body (EB) and monolayer differentiation configurations...

BACKGROUND: Recurrent spontaneous abortion (RSA) is defined as the loss of two or more consecutive intrauterine pregnancies with the same sexual partner in the first trimester. Despite its significance, the etiology and underlying mechanisms of RSA remain elusive. Defective decidualization is proposed as one of the potential causes of RSA, with abnormal decidualization leading to disturbances in trophoblast invasion function. METHODS: Decidual samples were collected from both RSA patients and healthy controls to assess BMP4 expression...

The long non-coding RNA (lncRNA) hepatocyte nuclear factor-1 alpha (HNF1A) antisense RNA 1 (HNF1A-AS1) is an important lncRNA for liver growth, development, cell differentiation, and drug metabolism. Like many lncRNAs, HNF1A-AS1 has multiple annotated alternative transcripts in the human genome. Several fundamental biological questions are still not solved: (1) How many transcripts really exist in biological samples, such as liver samples and liver cell lines? (2) What are the expression patterns of different alternative HNF1A-AS1 transcripts at different conditions, including during cell growth and development, after exposure to xenobiotics (such as drugs), and in disease conditions, such as metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD) cirrhosis, and obesity? (3) Does the siRNA used in previous studies knock down one or multiple transcripts? (4) Do different transcripts have the same or different functions for gene regulation? The presented data confirm the existence of several annotated HNF1A-AS1 transcripts in liver samples and cell lines, but also identify some new transcripts, which are not annotated in the Ensembl genome database...

BACKGROUND: Paired box 1 (PAX1) is a transcription factor and essential for the development of pharyngeal pouches-derived tissues, including thymus. PAX1 mutations are identified in Severe Combined Immunodeficiency (SCID) patients with Otofaciocervical Syndrome Type 2 (OTFCS2). However, despite the critical roles of PAX1 in embryonic development and diseases, detailed insights into its molecular mode of action are critically missing. METHODS: The repressing roles of PAX1 and SCID associated mutants on Wnt signaling pathway were investigated by luciferase reporter assays, qRT-PCR and in situ hybridization in HEK293FT, HCT116 cells and zebrafish embryos, respectively...

The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19. In the current study, we utilized islet organoids derived from human embryonic stem cells (hESCs), animal models and COVID-19 patients to discover that fibroblast growth factor 7 (FGF7) enhances ACE2 expression within the islets, facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion...

Dysfunction of the retinal pigment epithelium (RPE) is a common shared pathology in major degenerative retinal diseases despite variations in the primary etiologies of each disease. Due to their demanding and indispensable functional roles throughout the lifetime, RPE cells are vulnerable to genetic predisposition, external stress, and aging processes. Building upon recent advancements in stem cell technology for differentiating healthy RPE cells and recognizing the significant roles of small extracellular vesicles (sEV) in cellular paracrine and autocrine actions, we investigated the hypothesis that the RPE-secreted sEV alone can restore essential RPE functions and rescue photoreceptors in RPE dysfunction-driven retinal degeneration...

Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder characterized by a complex pathogenesis and limited treatment options. Yishen Huatan and Huoxue decoction (YHHD), as a traditional Chinese Medicine formula, has shown effectiveness in treating PCOS. However, the specific mechanisms by which YHHD exerts its therapeutic effects remain unclear. In this study, we performed to investigate the therapeutic effects of YHHD and quercetin on dehydroepiandrosterone-induced PCOS mice, and examine the effect of quercetin on the decidualization of T-HESCs under hyperinsulinemic conditions...

In vitro studies have demonstrated that the differentiation of embryonic stem cells (ESCs) into cardiomyocytes requires activation of caspases through the mitochondrial pathway. These studies have relied on synthetic substrates for activity measurements, which can be misleading due to potential none-specific hydrolysis of these substrates by proteases other than caspases. Hence, caspase-9 and caspase-3 activation are investigated during the differentiation of human ESCs (hESCs) by directly assessing caspase-9 and -3 cleavage...

Culturing of mouse and human embryonic stem cells (ESCs) in vitro was a major breakthrough in the field of stem cell biology. These models gained popularity very soon mainly due to their pluripotency. Evidently, the ESCs of mouse and human origin share typical phenotypic responses due to their pluripotent nature, such as self-renewal capacity and potency. The conserved network of core transcription factors regulates these responses. However, significantly different signaling pathways and upstream transcriptional networks regulate expression and activity of these core pluripotency factors in ESCs of both the species...

Mutations in CHCHD2 have been reported to be associated with familial Parkinson's disease (PD). We generated a human induced pluripotent stem cell (hiPSC) line by reprogramming dermal fibroblasts from a PD patient harboring a novel CHCHD2 mutation (c.434G > A, p.R145Q). This line exhibited human embryonic stem cell (hESC)-like clonal morphology, expression of undifferentiated stem cell markers, a normal karyotype and trilineage differentiation capacity and thus the potential to serve as a model for further investigating the underlying molecular mechanisms of CHCHD2 function in PD...

Human embryonic stem cells (hESCs) resemble the pluripotent epiblast cells found in the early postimplantation human embryo and represent the "primed" state of pluripotency. One factor that helps primed pluripotent cells retain pluripotency and prepare genes for differentiation is the transcription factor TCF7L1, a member of a small family of proteins known as T cell factors/Lymphoid enhancer factors (TCF/LEF) that act as downstream components of the WNT signaling pathway. Transcriptional output of the WNT pathway is regulated, in part, by the activity of TCF/LEFs in conjunction with another component of the WNT pathway, β-CATENIN...

Epigenetic defects caused by hereditary or de novo mutations are implicated in various human diseases. It remains uncertain whether correcting the underlying mutation can reverse these defects in patient cells. Here we show by the analysis of myotonic dystrophy type 1 (DM1)-related locus that in mutant human embryonic stem cells (hESCs), DNA methylation and H3K9me3 enrichments are completely abolished by repeat excision (CTG2000 expansion), whereas in patient myoblasts (CTG2600 expansion), repeat deletion fails to do so...

The human respiratory system is susceptible to a variety of diseases, ranging from chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis to acute respiratory distress syndrome (ARDS). Today, lung diseases represent one of the major challenges to the health care sector and represent one of the leading causes of death worldwide. Current treatment options often focus on managing symptoms rather than addressing the underlying cause of the disease. The limitations of conventional therapies highlight the urgent clinical need for innovative solutions capable of repairing damaged lung tissue at a fundamental level...

The myotendinous junction (MTJ) is a vulnerable region at the interface of skeletal muscle and tendon that forms an integrated mechanical unit. This study presents a technique for the spatially restrictive co-culture of human embryonic stem cell (hESC)-derived skeletal myocytes and primary tenocytes for two-dimensional modeling of the MTJ. Micropatterned lanes of extracellular matrix and a 2-well culture chamber define the initial regions of occupation. On day 1, both lines occupy less than 20% of the initially vacant interstitial zone, referred to henceforth as the junction...

Endometrial fibrosis is the histologic appearance of intrauterine adhesion (IUA). Emerging evidences demonstrated umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-exo) could alleviate endometrial fibrosis. But the specific mechanism is not clear. In this study, we explored the effect of UCMSC-exo on endometrial fibrosis, and investigated the possible role of miR-140-3p/FOXP1/Smad axis in anti-fibrotic properties of UCMSC-exo. UCMSC-exo were isolated and identified. Transforming growth factor-β (TGF-β) was used to induce human endometrial stromal cell (HESC) fibrosis...

No abstract text is available yet for this article.

Tuberous Sclerosis Complex (TSC) is a severe developmental disorder with various clinical effects, primarily caused by TSC2 gene mutations, often involving loss of function(Henske,et al., 2016).To explore role of TSC2 in human heart development, we successfully developed a TSC2 knockout (TSC2-/-) human embryonic stem cells (hESCs) line using CRISPR/Cas9 gene editing. This TSC2-/- hESC line maintained a normal karyotype, expressed pluripotency markers strongly, and could differentiate into all three germ layers in vivo...

Corneal transplantation represents the primary therapeutic approach for managing corneal endothelial dysfunction, but corneal donors remain scarce. Anterior chamber cell injection emerges as a highly promising alternative strategy for corneal transplantation, with pluripotent stem cells (PSC) demonstrating considerable potential as an optimal cell source. Nevertheless, only a few studies have explored the differentiation of functional corneal endothelial-like cells originating from PSC. In this investigation, a chemical-defined protocol was successfully developed for the differentiation of functional corneal endothelial-like cells derived from human embryonic stem cells (hESC)...

Since the revolutionary discovery of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka, the comparison between iPSCs and embryonic stem cells (ESCs) has revealed significant differences in their epigenetic states and developmental potential. A recent compelling study published in Nature by Buckberry et al. 1 demonstrated that a transient-naive-treatment (TNT) could facilitate epigenetic reprogramming and improve the developmental potential of human iPSCs (hiPSCs). However, the study characterized bulk hiPSCs instead of isolating clonal lines and overlooked the persistent expression of Sendai virus carrying exogenous Yamanaka factors...