The generation of beta-thalassemia (β-Thal) patient-specific induced pluripotent stem cells (iPSCs), subsequent homologous recombination-based gene correction disease-causing mutations/deletions in the β-globin (HBB), and their derived hematopoietic cell (HSC) transplantation offers an ideal therapeutic solution for treating this disease. However, differentiation efficiency gene-corrected β-Thal iPSCs has not been well evaluated previous studies. In study, we used latest gene-editing tool,...

Estrogen drives breast cancer (BCa) progression by directly activating estrogen receptor α (ERα). However, because of the stochastic nature gene transcription, it is important to study signaling pathway at single-cell level fully understand how ERα regulates transcription. Here, we performed transcriptome analysis on ERα-positive BCa cells following 17β-estradiol stimulation and reconstructed dynamic estrogen-responsive transcriptional network from discrete time points into a pseudotemporal...

Intravenously injected neural stem cells (NSCs) can infiltrate both primary and metastatic tumor sites; thus, they are attractive tumor-targeting vehicles for delivering anticancer agents. However, because the systemic distribution of NSCs involves normal organs might induce off-target actions leading to unintended side effects, clinical applications this approach is impeded. Given that vesicular stomatitis virus glycoprotein (VSV-G) promote formation multinucleated syncytia kill in a...

The human induced pluripotent stem cell (hiPSC) provides a breakthrough approach that helps overcoming ethical and allergenic challenges posed in application of neural cells (NSCs) targeted cancer gene therapy. However, the tumor‐tropic capacity hiPSC‐derived NSCs (hiPS‐NSCs) still has much room to improve. Here we attempted promote tumor tropism hiPS‐NSCs by manipulating activity endogenous miR‐199a/214 cluster is involved regulation hypoxia‐stimulated migration. We first developed...

The sperm chromatin structure assay (SCSA) is crucial for assessing male fertility. However, the predictive value of SCSA parameters, including DNA fragment indices (DFI) and percentages high stainability (HDS), outcomes artificial insemination by husband (AIH) remains controversial. This study aims to evaluate correlations between parameters aging as well other routine semen explore their prognostic powers on AIH Chinese infertile couples. A total 809 cycles were retrospectively analyzed....

The human induced pluripotent stem cell (iPSC) technique promises to provide an unlimited, reliable source of genetically matched cells for personalized therapy and disease modeling. Recently, it is observed that with ring chromosomes 13 or 17 autonomously correct the defects via compensatory uniparental disomy during cellular reprogramming iPSCs. This breakthrough finding suggests a potential therapeutic approach repair large-scale chromosomal aberrations. However, due scarceness chromosome...

Abstract Background Redirection of natural killer (NK) cells with chimeric antigen receptors (CAR) is attractive in developing off-the-shelf CAR therapeutics for cancer treatment. However, the site-specific integration a gene into NK remains challenging. Methods In present study, we genetically modified human induced pluripotent stem (iPSCs) zinc finger nuclease (ZFN) technology to introduce cDNA encoding an anti-EpCAM adeno-associated virus site 1, “safe harbour” transgene insertion genome,...

Neoadjuvant chemotherapy (NAC) induces a pathological complete response (pCR) in ~ 30% of patients with breast cancer. However, aberrant DNA methylation alterations are frequent events during cancer progression and acquisition chemoresistance. We aimed to characterize the inter- intra-tumor heterogeneity (MH) following NAC.DNA profiles spatially separated regions tumors before after NAC treatment were investigated using high-density microarray. Methylation levels genes interest further...

Chlamydia trachomatis (CT) infection is the most prevalent sexually transmitted bacterial disease worldwide. However, unlike that in female infertility, role of CT male infertility remains controversial. The objective this retrospective study was to explore impacts genital tract on sperm quality, acrosin activity, antisperm antibody levels, and inflammation a large cohort infertile males China. A total 7154 semen samples were collected from subjects, 416 whom positive (CT+ group) 6738...

Owing to their strong migratory capacity, tumor tropism, and inhibitory effect, neural stem cells (NSCs) have recently emerged as one of the most attractive gene delivery vectors for cancer therapy. However, further animal studies found that proportional NSC were distributed nontarget organs after intravenous injection nonspecific transgene expression led significant cytotoxic effects in these organs. Hence, an cassette controls within a site-specific manner is desired. Considering hypoxia...

The interaction between CD40 ligand (CD40L) and can directly inhibit growth of CD40-positive carcinoma cells may indirectly tumor through coordination immune responses. Many efforts in CD40L cancer gene therapy have been focused on direct transfer into malignant target cells. This vivo approach relies high-efficiency could be technically challenging for the treatment certain cancers, especially multisite metastases. We report herein an alternative means using tumor-homing property neural...

X chromosome inactivation (XCI) is a dosage compensation mechanism that silences the majority of genes on one in each female cell via random process. Skewed XCI relevant to many diseases, but leading it remains unclear. Human embryonic stem cells (hESCs) derived from inner mass (ICM) blastocyst-stage embryos have provided an excellent model system for understanding initiation and maintenance. Here, we hESC lines with or skewed patterns poor-quality investigated genome-wide copy number...

Capitalizing on liver tropism of adeno-associated viral (AAV) vectors, intravenous vector administration is commonly used to genetically modify hepatocytes, a strategy currently in clinical trials for number liver-based hereditary disorders. Although hepatocytes are known exhibit extensive phenotypic heterogeneity influenced by zonation and dietary cycle, there little data available the capacity, as well potential transcriptional dysregulation, AAV vectors specific cell types. To assess...

Recent progress in neural stem cell- (NSC-) based tumor-targeted gene therapy showed that NSC vectors expressing an artificially engineered viral fusogenic protein, VSV-G H162R, could cause tumor cell death specifically under acidic microenvironment by syncytia formation; however, the killing efficiency still had much room to improve. In view coexpression of another antitumoral with can augment bystander effect, a synthetic regulatory system triggers transgene expression fusion-inducible...

Recently, the clustered regularly interspaced short palindromic repeats (CRISPR) system has emerged as a powerful customizable artificial nuclease to facilitate precise genetic correction for tissue regeneration and isogenic disease modeling. However, previous studies reported substantial off-target activities of CRISPR in human cells, enormous putative sites are labor-intensive be validated experimentally, thus motivating bioinformatics methods rational design prediction its potential...

To determine the predictive values of sperm parameters pre- and post-processing by density gradient centrifugation for clinical pregnancy rates (CPRs) following artificial insemination husband (AIH) in infertile Chinese couples.A total 3,522 AIH cycles from 1,918 couples were retrospectively analyzed. The compared between pregnant non-pregnant groups further different etiological (Male-factor, Both-male-and-female-factor, Other-factor). Multivariate logistic regression analysis was performed...

The yeasts, including Saccharomyces cerevisiae and Pichia pastoris, are single-cell eukaryotic organisms that can serve as models for human genetic diseases hosts large scale production of recombinant proteins in current biopharmaceutical industry. Thus, efficient engineering tools yeasts great research economic values. Agrobacterium tumefaciens-mediated transformation (AMT) transfer T-DNA into yeast cells a method engineering. However, how the is transferred not well established yet. Here...

Turner syndrome (TS) with 45,X/46,XY mosaic karyotype is a rare sex chromosome disorder an occurrence of 0.15‰ at birth. We report the generation induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells Chinese adult male mosaicism. The iPSC retains original karyotype, expresses pluripotency markers and undergoes trilineage differentiation. Therefore, it offers unprecedented cellular model to investigate profound symptoms like infertility TS in male, serve as useful...

Background: To determine the independent prognostic factors and develop a multivariate logistic regression model for predicting successful pregnancy following artificial insemination by husband (AIH) in infertile Chinese couples. Methods: A total of 3,015 AIH cycles with superovulation from 1,853 couples were retrospectively analyzed. The clinical characteristics sperm parameters compared between pregnant non-pregnant groups. Multivariate analysis was performed to remove confounding create...

Abstract Background A 45,X monosomy (Turner syndrome, TS) is the only chromosome haploinsufficiency compatible with life. Nevertheless, surviving TS patients still suffer from increased morbidity and mortality, around one-third of them subjecting to heart abnormalities. How loss one X drive these conditions remains largely unknown. Methods Here, we have generated cardiomyocytes (CMs) wild-type patient-specific induced pluripotent stem cells profiled mRNA, lncRNA circRNA expression in cells....

The testicular disorder of sex development (TDSD) is a rare condition characterized by male appearance with female karyotype. most frequent cause TDSD misplacement the determining region Y (SRY) gene on X chromosome. Here, we report generation an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells patient SRY-positive 46,XX TDSD. This offers unprecedented cellular model to investigate profound manifestations like infertility reversal patients, and serves as...

Abstract Estrogen regulates diverse physiological effects and drives breast tumor progression by directly activating estrogen receptor α (ERα). However, due to the stochastic nature of gene transcription resulting heterogeneous cellular response, it is important investigate estrogen-stimulated expression profiles at single-cell level in order fully understand how ERα cancer cells. In this study, we performed transcriptome analysis on ERα-positive cell lines following 17β-estradiol...