Physiological Modeling of the Vascularized Human Lung Organoid.

Studies using human lung organoids (hLO) have focused on differentiation of lung epithelial subtypes into distal alveolar unit. A major question has been whether introducing endothelial cells (EC) and resultant vascularization alter development of hLO. We describe herein a method for vessel infiltration of hLO in which we determined differences of these hLOs with standard avascular hLOs.

Trapa Bispinosa Roxb. Inhibits the Insulin-Dependent AKT/WNK1 Pathway to Induce Autophagy in Mice with Type 2 Diabetes.

Purpose: To elucidate the antiglycation activity of Trapa bispinosa Roxb. extract (TBE) and the related mechanism using a mouse model with type 2 diabetes.

Materials And Methods: We prepared control mice by giving them a normal diet, leptin-deficient ob/ob mouse (ob/ob mice) with a normal diet (normal ob/ob mice), and ob/ob mice with a diet containing TBE (TBE ob/ob mice).

Stage-specific action of Runx1 and GATA3 controls silencing of PU.1 expression in mouse pro-T cells.

PU.1 (encoded by Spi1), an ETS-family transcription factor with many hematopoietic roles, is highly expressed in the earliest intrathymic T cell progenitors but must be down-regulated during T lineage commitment. The transcription factors Runx1 and GATA3 have been implicated in this Spi1 repression, but the basis of the timing was unknown.

Transcription factors regulate early T cell development via redeployment of other factors: Functional dynamics of constitutively required factors in cell fate decisions.

Establishment of cell lineage identity from multipotent progenitors is controlled by cooperative actions of lineage-specific and stably expressed transcription factors, combined with input from environmental signals. Lineage-specific master transcription factors activate and repress gene expression by recruiting consistently expressed transcription factors and chromatin modifiers to their target loci. Recent technical advances in genome-wide and multi-omics analysis have shed light on unexpected mechanisms that underlie more complicated actions of transcription factors in cell fate decisions.

Runx1 and Runx3 drive progenitor to T-lineage transcriptome conversion in mouse T cell commitment via dynamic genomic site switching.

Runt domain-related (Runx) transcription factors are essential for early T cell development in mice from uncommitted to committed stages. Single and double Runx knockouts via Cas9 show that target genes responding to Runx activity are not solely controlled by the dominant factor, Runx1. Instead, Runx1 and Runx3 are coexpressed in single cells; bind to highly overlapping genomic sites; and have redundant, collaborative functions regulating genes pivotal for T cell development.

Impaired Autophagy in Retinal Pigment Epithelial Cells Induced from iPS Cell of Distal Myopathy with Rimmed Vacuole Patient.

Objective: We generated induced pluripotent stem (iPS) cells from a patient with distal myopathy with rimmed vacuoles (DMRV), in which sialic acids synthesis is reported to be defective. In this study, we examined whether the differentiation to retinal pigment epithelial (RPE) cells and autophagy was affected in the patient derived cells.

Methods: Patient derived iPS cells were established through the transduction of re-programming factors into peripheral mononuclear cells via retrovirus vectors.

AMBRA1 controls antigen-driven activation and proliferation of naive T cells.

AMBRA1 (activating molecule in Beclin1-regulated autophagy) is a member of the BECN1 (BECLIN1) protein complex, and it plays a role in autophagy, cell death, tumorigenesis and proliferation. We recently reported that on T-cell receptor (TCR) stimulation, AMBRA1 controlled both autophagy and the cell cycle with metabolic regulation. Accumulating evidence has shown that autophagy and metabolic control are pivotal for T-cell activation, clonal expansion and effector/memory cell fate decision.

AMBRA1 is involved in T cell receptor-mediated metabolic reprogramming through an ATG7-independent pathway.

Metabolic reprogramming contributes to dynamic alteration of cell functions and characteristics. In T cells, TCR-mediated signaling evokes metabolic reprogramming and autophagy. AMBRA1 is known to serve in the facilitation of autophagy and quality control of mitochondria, but the role of AMBRA1 in T cell metabolic alteration is unknown.

Interaction of a novel fluorescent GTP analogue with the small G-protein K-Ras.

A novel fluorescent guanosine 5'-triphosphate (GTP) analogue, 2'(3')-O-{6-(N-(7-nitrobenz-2-oxa-l,3-diazol-4-yl)amino) hexanoic}-GTP (NBD-GTP), was synthesized and utilized to monitor the effect of mutations in the functional region of mouse K-Ras. The effects of the G12S, A59T and G12S/A59T mutations on GTPase activity, nucleotide exchange rates were compared with normal Ras. Mutation at A59T resulted in reduction of the GTPase activity by 0.