The unique spliceosome signature of human pluripotent stem cells is mediated by SNRPA1, SNRPD1, and PNN.

Spliceosomes are the core host of pre-mRNA splicing, allowing multiple protein isoforms to be produced from a single gene. Herein, we reveal that spliceosomes are more abundant in human pluripotent stem cells (hPSs), including human embryonic stem cells (hESs) and human induced pluripotent stem cells (hiPSs), than non-hPSs, and their presence is associated with high transcriptional activity. Supportively, spliceosomal components involved in the catalytically active pre-mRNA splicing step were mainly co-localized with hPS spliceosomes.

Interferon β protects against lethal endotoxic and septic shock through SIRT1 upregulation.

Lipopolysaccharide (LPS), an endotoxin derived from gram-negative bacteria, promotes the secretion of proinflammatory cytokines and mediates endotoxemia through activation of mitogen activated protein kinases, NF-κB, and interferon regulatory factor-3. Silent information regulator transcript-1 (SIRT1), an NAD-dependent deacetylase, mediates NF-κB deacetylation, and inhibits its function. SIRT1 may affect LPS-mediated signaling pathways and endotoxemia.

Endothelial progenitor cells from human dental pulp-derived iPS cells as a therapeutic target for ischemic vascular diseases.

Human dental pulp cells (hDPCs) are a valuable source for the generation of patient-specific human induced pluripotent stem cells (hiPSCs). An advanced strategy for the safe and efficient reprogramming of hDPCs and subsequent lineage-specific differentiation is a critical step toward clinical application. In present research, we successfully generated hDPC-iPSCs using only two non-oncogenic factors: Oct4 and Sox2 (2F hDPC-hiPSCs) and evaluated the feasibility of hDPC-iPSCs as substrates for endothelial progenitor cells (EPCs), contributing to EPC-based therapies.

Nicotinamide overcomes pluripotency deficits and reprogramming barriers.

Crosstalk between intracellular signaling pathways has been extensively studied to understand the pluripotency of human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells (hiPSCs); however, the contribution of NAD(+) -dependent pathways remains largely unknown. Here, we show that NAD(+) depletion by FK866 (a potent inhibitor of NAD(+) biosynthesis) was fatal in hPSCs, particularly when deriving pluripotent cells from somatic cells and maintaining pluripotency. NAD and its precursors (nicotinamide [NAM] and nicotinic acid) fully replenished the NAD(+) depletion by FK866 in hPSCs.

Lipopolysaccharide induces CD38 expression and solubilization in J774 macrophage cells.

CD38, an ADP ribosyl cyclase, is a 45 kDa type II transmembrane protein having a short N-terminal cytoplasmic domain and a long C-terminal extracellular domain, expressed on the surface of various cells including macrophages, lymphocytes, and pancreatic β cells. It is known to be involved in cell adhesion, signal transduction and calcium signaling. In addition to its transmembrane form, CD38 is detectable in biological fluids in soluble forms.

NAADP mediates insulin-stimulated glucose uptake and insulin sensitization by PPARγ in adipocytes.

Insulin stimulates glucose uptake through the membrane translocation of GLUT4 and GLUT1. Peroxisome proliferator-activated receptor γ (PPARγ) enhances insulin sensitivity. Here, we demonstrate that insulin stimulates GLUT4 and GLUT1 translocation, and glucose uptake, by activating the signaling pathway involving nicotinic acid adenine dinucleotide phosphate (NAADP), a calcium mobilizer, in adipocytes.

Connexin-43 hemichannels mediate cyclic ADP-ribose generation and its Ca2+-mobilizing activity by NAD+/cyclic ADP-ribose transport.

The ADP-ribosyl cyclase CD38 whose catalytic domain resides in outside of the cell surface produces the second messenger cyclic ADP-ribose (cADPR) from NAD(+). cADPR increases intracellular Ca(2+) through the intracellular ryanodine receptor/Ca(2+) release channel (RyR). It has been known that intracellular NAD(+) approaches ecto-CD38 via its export by connexin (Cx43) hemichannels, a component of gap junctions.