In order to understand the molecular mechanisms of DN thymocyte development, it may be also of use to clarify how these developmental processes are regulated in terms of their entire gene expression, to which cell differentiation is ultimately ascribed.
Expression profiling of immature thymocytes revealed a novel homeobox gene that regulates double-negative thymocyte development.
No sample metadata fields
View SamplesThe molecular chaperons FK506-binding proteins (Fkbps) comprise one of three families of peptidyl prolyl isomerases, which promote the transition between cis- and trans-conformations of peptidyl prolyl bonds. Mouse Fkbp family is composed of at least 15 members, but the functions of the large family in cell proliferation and differentiation remain elusive. During myoblast differentiation, the cells need to exit the cell cycle before fusion and terminal differentiation to form myotubes. The clear distinction between proliferation and differentiation provides an ideal model with which to investigate the roles of Fkbps in these two cell biological events. We found that depletion of FkbpC in mouse myoblasts delayed the exit from the cell cycle and expression of myotube-specific genes, whereas its overexpression caused opposite effects. At a mechanistic level, our study revealed a crucial function of FkbpC in Cdk4 activation during myoblast proliferation. Cdk4 undergoes conformational changes in the HSP90/Cdc37/Cdk4 complex as a prerequisite for activation through binding to CyclinD1 accompanied by phosphorylation. Our results showed that FkbpC depletion released Cdk4 from the HSP90 complex, which increased the Cdk4/CyclinD1 complex in myoblasts and sustained high levels of phosphorylated Cdk4 and Rb during differentiation. These results explain the delayed cell cycle exit and differentiation in the depleted cells. In addition, after synchronizing the cell cycle of myoblasts we found dynamic changes of the amounts of FkbpC and Cdk4 in the HSP90 complex during the G1/S transition. Knockout mice of FkbpC demonstrated delayed muscle regeneration after chemical damage, providing an in vivo evidence for the essential role of FkbpC in muscle differentiation. Collectively, our study uncovered FkbpC's critical function as a novel switch regulating the transition from proliferation to differentiation through controlling one of the central regulators of proliferation, Cdk4. Overall design: mRNA profiles of Fkbp4 knockdown, Fkbp5 knockdown and control C2C12 cells at d0, d3 and d5 were generated by using Illumina HiSeq2500.
Promotion of Myoblast Differentiation by Fkbp5 via Cdk4 Isomerization.
Specimen part, Cell line, Subject, Time
View Samplescompare the gene expression profile between irradiated Lin-Sca-1+c-Kit+ (LSK) cells from mouse bone marrow reconstituted with wild type and necdin null fetal liver cells
Necdin, a p53 target gene, regulates the quiescence and response to genotoxic stress of hematopoietic stem/progenitor cells.
Specimen part, Treatment
View SamplesWe analyzed gene expression profiles of self-organizing, multi-cellular, 3D liver organoids derived by co-culture of induced Pluripotent Stem Cell and stromal progenitors. We report the RNA-seq results of liver organoid at day0, day2, day4, day6 of co-culture. We also report RNA-seq results of constituent of the liver organoid, which are human iPSC at hepatic specification stage, human Mesenchymal stem cells derived from bone marrow, human umbilical vein endothelial cell. As controls, we also report RNS-seq results of un-differentiated human iPSC, human iPSC at definitive endoderm stage, human liver tissue, and primary cultured human hepatocytes isolated from unused donor livers. Overall design: mRNA profiles of liver organoids and their constituents were generated by deep sequencing, in triplicate, using Illumina HiSeq 2500.
Paracrine signals regulate human liver organoid maturation from induced pluripotent stem cells.
Subject, Time
View Samplesgene-expression change along with differentiation stage from human iPS cells to astrocytes is unkown.
Modeling Alzheimer's disease with iPSCs reveals stress phenotypes associated with intracellular Aβ and differential drug responsiveness.
Specimen part
View SamplesOligomeric forms of amyloid-beta peptide (Abeta) are presumed to play a pivotal role in the pathogenesis of Alzheimers disease (AD). However, it is still unclear how Abeta oligomers contribute to AD pathogenesis in patient neural cells. We generated induced pluripotent stem cells (iPSCs) from a familial AD patient and differentiated them into neural cells. Abeta oligomers were accumulated in neural cells of AD bearing amyloid precursor protein (APP)-E693delta mutation.
Modeling Alzheimer's disease with iPSCs reveals stress phenotypes associated with intracellular Aβ and differential drug responsiveness.
Specimen part
View SamplesCircadian rhythms regulate cell proliferation and differentiation; however, little is known about their roles in myogenic differentiation. Our synchronized differentiation studies demonstrate that myoblast proliferation and subsequent myotube formation by cell fusion occur in circadian manners. We found that one of the core regulators of circadian rhythms Cry2, but not Cry1, is critical for the circadian patterns of these two critical steps in myogenic differentiation. This is achieved through the specific interaction between Cry2 and Bclaf1, which stabilizes mRNAs encoding cyclin D1, a G1/S phase transition regulator, and Tmem176b, a transmembrane regulator for myogenic cell fusion. Myoblasts lacking Cry2 display premature cell cycle exit and form short myotubes due to inefficient cell fusion. Consistently, muscle regeneration is impaired in Cry2-/- mice. Bclaf1 knockdown recapitulated the phenotypes of Cry2 knockdown: early cell cycle exit and inefficient cell fusion. This study uncovers a post-transcriptional regulation of myogenic differentiation by circadian rhythms. Overall design: mRNA profiles of Cry1 knockdown, Cry2 knockdown and control C2C12 cells at d0, d3 and d5 were generated by using Illumina HiSeq2500.
Cry2 Is Critical for Circadian Regulation of Myogenic Differentiation by Bclaf1-Mediated mRNA Stabilization of Cyclin D1 and Tmem176b.
Specimen part, Cell line, Subject
View SamplesHuman pluripotent stem cells (hPSCs) such as embryonic stem cells and induced pluripotent stem cells are promising materials for cell-based regenerative therapies to heart diseases. However, until realization there are many hurdles such as high efficiency of cardiac differentiation of hPSCs and production of clinical-grade cardiac cells derived from hPSCs. Here, we show that a novel small molecule KY02111 robustly enhances differentiation to functional cardiomyocytes from hPSCs.
A small molecule that promotes cardiac differentiation of human pluripotent stem cells under defined, cytokine- and xeno-free conditions.
Specimen part, Cell line
View Samples<Objective> To compare gene expression in labial salivary glands (LSG) of IgG4-related disease (IgG4-RD) with Sjgrens syndrome (SS).
DNA microarray analysis of labial salivary glands in IgG4-related disease: comparison with Sjögren's syndrome.
Sex, Specimen part
View SamplesTo examine the molecular phenotype of hypoxic cardiomyocytes in their native environment, we isolated tdTomato+ cardiomyocytes from fresh cryosections using laser microdissection. And perform gene expression analysis using RNA sequencing (RNA-seq).
Hypoxia fate mapping identifies cycling cardiomyocytes in the adult heart.
No sample metadata fields
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