Human pluripotent stem cells (hPSCs) exhibit very limited contribution to interspecies chimeras. One explanation is that the conventional hPSCs are in a primed state and so unable to form chimeras in pre-implantation embryos. Here, we show that the conventional hPSCs undergo rapid apoptosis when injected into mouse pre-implantation embryos.
View Article and Find Full Text PDFLithium-sulfur batteries are among the most promising low-cost, high-energy-density storage devices. However, the inability to host a sufficient amount of sulfur in the cathode while maintaining good electrochemical stability under a lean electrolyte condition has limited the progress. The main cause of these challenges is the sensitivity of the sulfur cathode to the cell-design parameters (i.
View Article and Find Full Text PDFMiR-122 is the most abundant miRNA in the human liver accounting for 52% of the entire hepatic miRNome. Previous studies have demonstrated that miR-122 is a valuable therapeutic target for liver diseases, including viral hepatitis, fibrosis, steatosis, and hepatocarcinoma. Here, we constructed a miR-122 doxycycline-inducible expression human embryonic stem cell line WAe001-A-15 using the piggyBac transposon system.
View Article and Find Full Text PDFGlycogen debranching enzyme (GDE) plays a critical role in glycogenolysis. Mutations in the GDE gene are associated with a metabolic disease known as glycogen storage disease type III (GSDIII). We generated a mutant GDE human embryonic stem cell line, WAe001-A-14, using the CRISPR/Cas9 editing system.
View Article and Find Full Text PDFThe ASS1 gene encodes argininosuccinate synthetase-1, a cytosolic enzyme with a critical role in the urea cycle. Mutations are found in all ASS1 exons and cause the autosomal recessive disorder citrullinemia. Using CRISPR/Cas9-editing, we established the WAe001-A-13 cell line, which was heterozygous for an ASS1 mutation, from the human embryonic stem cell line H1.
View Article and Find Full Text PDFThe ATP-sensitive potassium channel is an octameric complex, and one of its subunits, namely Kir6.2, is encoded by the KCNJ11 gene. Mutations in KCNJ11 result in hyperinsulinism or diabetes mellitus, associated with abnormal insulin secretion.
View Article and Find Full Text PDFThe MEN1 gene is cytogenetically located at 11q13.1 and encodes the nuclear protein menin, which is involved in cell proliferation, apoptosis, differentiation, and metabolism. Here, we generated two MEN1 knockout human embryonic stem cell lines, WAe001-A-4 and WAe001-A-5, by targeting exon-2 and exon-9 of MEN1 using the CRISPR/Cas9 technique.
View Article and Find Full Text PDFmiR-122 is the most abundant miRNA in the human liver, accounting for 52% of the entire hepatic miRNome. Previous studies have demonstrated that miR-122 plays key roles in hepatocyte growth, metabolism, and homeostasis. Here, we created three miR-122 knockout human embryonic stem cell line lines, WAe001-A-7, WAe001-A-8, and WAe001-A-9, using the CRISPR/Cas9 technique.
View Article and Find Full Text PDFThe gene asialoglycoprotein receptor 1 (ASGR1) encodes a subunit of the asialoglycoprotein receptor. Here we report the generation of a human embryonic stem cell line WAe001-A-6 harbouring homozygous ASGR1 mutations using CRISPR/Cas9. The mutation involves a 37bp deletion, resulting in a frame shift.
View Article and Find Full Text PDFPolycomb repressive complex 2 and the epigenetic mark that it deposits, H3K27me3, are evolutionarily conserved and play critical roles in development and cancer. However, their roles in cell fate decisions in early embryonic development remain poorly understood. Here we report that knockout of polycomb repressive complex 2 genes in human embryonic stem cells causes pluripotency loss and spontaneous differentiation toward a meso-endoderm fate, owing to de-repression of BMP signalling.
View Article and Find Full Text PDFThe gene of ATP-binding cassette subfamily C member 8 (Abcc8) is cytogenetically located at 11p15.1 and encodes the sulfonylurea receptor (SUR1). SUR1 is a subunit of ATP-sensitive potassium channel (KAPT) in the β-cell regulating insulin secretion.
View Article and Find Full Text PDFThe gene of ATP-binding cassette subfamily C member 8 (Abcc8) is cytogenetically located at 11p15.1 and encodes the sulfonylurea receptor (SUR1). SUR1 is a subunit of ATP-sensitive potassium channel (KAPT) in the β-cell regulating insulin secretion.
View Article and Find Full Text PDFRecent studies have boosted our understanding of long noncoding RNAs (lncRNAs) in numerous biological processes, but few have examined their roles in somatic cell reprogramming. Through expression profiling and functional screening, we have identified that the large intergenic noncoding RNA p21 (lincRNA-p21) impairs reprogramming. Notably, lincRNA-p21 is induced by p53 but does not promote apoptosis or cell senescence in reprogramming.
View Article and Find Full Text PDFVitamin C, a micronutrient known for its anti-scurvy activity in humans, promotes the generation of induced pluripotent stem cells (iPSCs) through the activity of histone demethylating dioxygenases. TET hydroxylases are also dioxygenases implicated in active DNA demethylation. Here we report that TET1 either positively or negatively regulates somatic cell reprogramming depending on the absence or presence of vitamin C.
View Article and Find Full Text PDFThe mechanism and kinetics for the gas-phase hydrolysis of N(2)O(4) isomers have been investigated at the CCSD(T)/6-311++G(3df,2p)//B3LYP/6-311++G(3df,2p) level of theory in conjunction with statistical rate constant calculations. Calculated results show that the contribution from the commonly assumed redox reaction of sym-N(2)O(4) to the homogeneous gas-phase hydrolysis of NO(2) can be unequivocally ruled out due to the high barrier (37.6 kcal/mol) involved; instead, t-ONONO(2) directly formed by the association of 2NO(2), was found to play the key role in the hydrolysis process.
View Article and Find Full Text PDFReprogramming somatic cells to become induced pluripotent stem cells (iPSCs) by using defined factors represents an important breakthrough in biology and medicine, yet remains inefficient and poorly understood. We therefore devised synthetic factors by fusing the VP16 transactivation domain to OCT4 (also known as Pou5f1), NANOG and SOX2, respectively. These synthetic factors could reprogramme both mouse and human fibroblasts with enhanced efficiency and accelerated kinetics.
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