A new determination method of interatomic potential for sodium silicate glass simulations

An interatomic potential for the classical molecular dynamics (MD) simulation of sodium silicate glasses was proposed. The ionic charges for this interatomic potential were determined by Mulliken population analysis via the density functional theory (DFT) calculation of alkali silicate crystals. The Si-O interatomic potential energy curve was determined by molecular orbital (MO) calculation of SiO2 +. The results of classical MD simulations using the new interatomic potential were consistent with the experimental trends in interatomic distance, thermal expansion coefficient, molar volume, Si-O-Si bond angle distribution, and Qn ratio with respect to the sodium composition of the silicate glass. The proposed interatomic potential improves the reproducibility of the ring size distribution in silicate glasses compared to conventional potentials

Silencing of p53 and CDKN1A establishes sustainable immortalized megakaryocyte progenitor cells from human iPSCs

iPS細胞を用いた人工血小板の作製の効率化に成功 血小板のテイラーメイド医療に向けた一歩. 京都大学プレスリリース. 2021-12-03.Platelet transfusions are critical for severe thrombocytopenia but depend on blood donors. The shortage of donors and the potential of universal HLA-null platelet products have stimulated research on the ex vivo differentiation of human pluripotent stem cells (hPSCs) to platelets. We recently established expandable immortalized megakaryocyte cell lines (imMKCLs) from hPSCs by transducing MYC, BMI1, and BCL-XL (MBX). imMKCLs can act as cryopreservable master cells to supply platelet concentrates. However, the proliferation rates of the imMKCLs vary with the starting hPSC clone. In this study, we reveal from the gene expression profiles of several MKCL clones that the proliferation arrest is correlated with the expression levels of specific cyclin-dependent kinase inhibitors. Silencing CDKN1A and p53 with the overexpression of MBX was effective at stably inducing imMKCLs that generate functional platelets irrespective of the hPSC clone. Collectively, this improvement in generating imMKCLs should contribute to platelet industrialization and platelet biology

Transient activation of c-MYC expression is critical for efficient platelet generation from human induced pluripotent stem cells

A specific kinetic pattern of c-MYC expression is essential for optimal generation of functional platelets from human induced pluripotent stem cells

Immortalization of Erythroblasts by c-MYC and BCL-XL Enables Large-Scale Erythrocyte Production from Human Pluripotent Stem Cells

増殖能の盛んな赤血球前駆細胞による赤血球を大量生産するための方法確立. 京都大学プレスリリース. 2013-12-06.The lack of knowledge about the mechanism of erythrocyte biogenesis through self-replication makes the in vitro generation of large quantities of cells difficult. We show that transduction of c-MYC and BCL-XL into multipotent hematopoietic progenitor cells derived from pluripotent stem cells and gene overexpression enable sustained exponential self-replication of glycophorin A+ erythroblasts, which we term immortalized erythrocyte progenitor cells (imERYPCs). In an inducible expression system, turning off the overexpression of c-MYC and BCL-XL enabled imERYPCs to mature with chromatin condensation and reduced cell size, hemoglobin synthesis, downregulation of GCN5, upregulation of GATA1, and endogenous BCL-XL and RAF1, all of which appeared to recapitulate normal erythropoiesis. imERYPCs mostly displayed fetal-type hemoglobin and normal oxygen dissociation in vitro and circulation in immunodeficient mice following transfusion. Using critical factors to induce imERYPCs provides a model of erythrocyte biogenesis that could potentially contribute to a stable supply of erythrocytes for donor-independent transfusion