Four healthy human volunteers underwent an acute bout of resistance exercise with the right leg at 2 pm. Biopsies were removed from the Vastus Lateralis muscle 6 h (8 pm) and 18 h (8 am) after exericise
Time- and exercise-dependent gene regulation in human skeletal muscle.
No sample metadata fields
View SamplesDuring embryogenesis, cell specification and tissue formation is directed by the concentration and temporal presentation of morphogens, and similarly, pluripotent embryonic stem cells differentiate in vitro into various phenotypes in response to morphogen treatment. Embryonic stem cells are commonly differentiated as three dimensional spheroids called embryoid bodies (EBs); however, differentiation within EBs is typically heterogeneous and disordered. Here we show that spatiotemporal control of microenvironmental cues embedded directly within EBs enhances the homogeneity, synchrony and organization of differentiation. Degradable polymer microspheres releasing retinoic acid within EBs induce the formation of cystic spheroids closely resembling the early streak mouse embryo, with an exterior of visceral endoderm enveloping an epiblast layer. These results demonstrate that controlled morphogen presentation to stem cells more efficiently directs cell differentiation and tissue formation, thereby improving developmental biology models and enabling the development of regenerative medicine therapies and cell diagnostics.
Homogeneous and organized differentiation within embryoid bodies induced by microsphere-mediated delivery of small molecules.
No sample metadata fields
View SamplesIdentfification of MEF2A target genes using ChIP-exo and RNA-seq in skeletal muscle and primary cardiomyocytes. MEF2 plays a profound role in the regulation of transcription in cardiac and skeletal muscle lineages. To define the overlapping and unique MEF2A genomic targets, we utilized ChIP-exo analysis of cardiomyocytes and skeletal myoblasts. Of the 2783 and 1648 MEF2A binding peaks in skeletal myoblasts and cardiomyocytes, respectively, 294 common binding sites were identified. Genomic targets were compared to differentially expressed genes in RNA-seq analysis of MEF2A depleted myogenic cells. Overall design: The effect of MEF2A gene silencing on gene expression in myoblasts was assessed at 48 hr DM. Up and downregulated genes were then compared to MEF2A target genes identified in ChIP-exo analysis of 48 hr DM C2C12 myoblasts cells and primary cardiomyocytes.
Global MEF2 target gene analysis in cardiac and skeletal muscle reveals novel regulation of DUSP6 by p38MAPK-MEF2 signaling.
No sample metadata fields
View SamplesIn homeostasis of adult vertebrate tissues, stem cells are thought to self-renew by infrequent and asymmetric divisions that generate another stem cell daughter and a progenitor daughter cell committed to differentiate. This model is based largely on in vivo invertebrate or in vitro mammal studies. Here we examine the dynamic behaviour of adult hair follicle stem cells in their normal setting by employing mice with repressible H2B-GFP expression to track cell divisions and Cre inducible mice to perform long-term single cell lineage tracing. We provide direct evidence for the infrequent stem cell division model in intact tissue. Moreover, we find that differentiation of progenitor cells occurs at different times and tissue locations than self-renewal of stem cells. Distinct fates of differentiation or self-renewal are assigned to individual cells in a temporal-spatial manner. We propose that large clusters of tissue stem cells behave as populations, whose maintenance involves unidirectional daughter-cell fate decisions.
Distinct self-renewal and differentiation phases in the niche of infrequently dividing hair follicle stem cells.
Specimen part
View SamplesProfile of RNA expression in a C-33A cell line derived from an HPV negative cervical carcinoma in the presence or absence of HPV1 E2 expression. Overall design: mRNA profiles of C-33A cells in presence or absence of HPV1 E2 expression were generated by deep sequencing using Illumina GAIIx. Two samples (no replicates). One control and one experimental.
The effect of Rho kinase inhibition on long-term keratinocyte proliferation is rapid and conditional.
No sample metadata fields
View SamplesQuiescent hair follicle (HF) bulge stem cells (SCs) differentiate to early progenitor (EP) hair germ (HG) cells, which divide to produce transit-amplifying (TA) matrix cells. EPs can revert to SCs upon injury, but whether this de-differentiation occurs in normal HF homeostasis (hair cycle), and the mechanisms regulating both differentiation and de-differentiation are unclear. Here we use lineage tracing, gain of function, transcriptional profiling, and functional assays to examine the role of observed endogenous Runx1 level changes in the hair cycle. We find that forced Runx1 expression implements hair degeneration (catagen) and simultaneously promotes changes in the quiescent bulge SC transcriptome towards a cell-state resembling the EP HG fate. This cell-state transition is functionally reversible. We propose that SC differentiation and de-differentiation are likely to occur during normal HF degeneration and niche restructuring in response to changes in endogenous Runx1 levels associated with SC location with respect to the niche.
High Runx1 levels promote a reversible, more-differentiated cell state in hair-follicle stem cells during quiescence.
Specimen part
View SamplesSamples of primary tumors collected from 23 ovarian cancer patients
Machine learning predicts individual cancer patient responses to therapeutic drugs with high accuracy.
Sex, Specimen part, Disease
View SamplesGene regulatory networks that govern hematopoietic stem cells (HSC) and leukemiainitiating cells (L-IC) are deeply entangled. Thus, the discovery of compounds that target L-IC while sparing HSC is an attractive but difficult endeavor. Presently, most drug discovery approaches fail to counter-screen compounds against normal hematopoietic stem/progenitor cells (HSPC) to assess therapeutic index. Here, we present a combined in vitro and in vivo strategy to identify compounds specific to L-IC in acute myeloid leukemia (AML). A high-throughput screen of 4000 compounds on novel leukemia cell lines derived from human experimental leukemogenesis models yielded 80 hits, of which most were toxic to normal HSPC. Of the 10 compounds that passed this initial filter, we chose to characterize a single compound, kinetic riboside (KR), on AML L-IC and HSPC. KR demonstrated comparable efficacy to standard therapies against 63 primary AMLs. In vitro, KR effectively targeted the L-IC-enriched CD34+CD38- AML fraction, while sparing normal HSPC enriched fractions, although these effects were mitigated on HSC assayed in vivo, and highlights the importance of in vivo L-IC and HSC assays to measure function. Overall, we provide a novel approach to screen large drug libraries for the discovery of anti-L-IC compounds for human leukemias.
A small molecule screening strategy with validation on human leukemia stem cells uncovers the therapeutic efficacy of kinetin riboside.
Cell line, Treatment
View SamplesWe use genetic manipulations of regulators representing different pathways to examine whether transcriptomes progressively resemble dietary restriction when multiple regulators are perturbed.
A Systems Approach to Reverse Engineer Lifespan Extension by Dietary Restriction.
Specimen part
View SamplesThis data series was used for two separate studies. The initial study was aimed to idenify expression changes brought about by the Cecr2Gt45Bic mutation during neural closure. The study included two different strains, BALB/cCrl in which Cecr2GT45Bic shows a neural tube defect phenotype and FVB/N in which Cecr2Gt45Bic does not manifest neural closure defects. The second was to idenify strain specific expression differences present during neural closure of the mouse embryo between BALB/cCrl and FVB/N in order to identify candidate modifiers of the Cecr2Gt45Bic neural tube defect. Relevant abstracts are included below.
Strain-specific modifier genes of Cecr2-associated exencephaly in mice: genetic analysis and identification of differentially expressed candidate genes.
Sex, Specimen part
View Samples