Normal development requires tight regulation of cell proliferation and cell death. Here, we investigated these control mechanisms in the hyaloid vessels, a temporary vascular network in the mammalian eye that requires a Wnt/ß-catenin response for scheduled regression. Transcriptome analysis of the postnatal day 5 mouse hyaloid showed expression of several Wnt pathway proteins. We investigated whether the hyaloid Wnt response was linked to the oncogene Myc, and the cyclin-dependent kinase inhibitor P21 (CDKN1A), both established regulators of cell cycle progression and cell death. Our analysis showed that the Wnt pathway coreceptors LRP5 and LRP6 have overlapping activities mediating the Wnt/ß-catenin signaling in hyaloid vascular endothelial cells (VECs). We also showed that both Myc and Cdkn1a are downstream of the Wnt response and are required for hyaloid regression but for different reasons. Conditional deletion of Myc in VECs suppressed both proliferation and cell death. By contrast, conditional deletion of Cdkn1a resulted in VEC over-proliferation that countered the effects of cell death on regression. When combined with analysis of MYC, and P21 protein levels, this analysis suggests that a Wnt/ß-catenin, MYC-P21 pathway regulates scheduled hyaloid vessel regression. Overall design: Hyaloid vascular preparations from postnatal day 5 mice were harvested in cold PBS and RNA extracted in Tri Reagent. RNA amplifcation was performed on total RNA before cDNA library was made. Samples were then sequenced using Illimina HiSeq2500 to obtain 25-30 million paired-end reads.
Developmental vascular regression is regulated by a Wnt/β-catenin, MYC and CDKN1A pathway that controls cell proliferation and cell death.
Specimen part, Subject
View SamplesIL17-producing ?d T cells (?d T17) mainly develop in the prenatal phase and persist as long-living self-renewing effector cell in all kind of tissues. They express polyclonal T-cell receptors (TCR), comprising public V?4+ and V?6+ TCRs with germline-like rearrangements. In particular, V?6+ T cells have recently been found in a variety of tissues including enthesis, gingiva or skin. However, their exchange between tissues and the mechanisms of tissue-specific adaptation and residency remain poorly understood. Here, we profiled V?6+ T cells isolated from thymus, peripheral lymph nodes (pLN) and skin through single-cell RNA-seq technology and compared those to V?4+ T cells. Our data demonstrated that V?6+ T cells formed highly homogenous cell populations that could be separated by tissue-specific gene expression signatures. Overall design: Sort V?4 and V?6 ?dT cells from peripheral lymph nodes, ear skin and thymus, then do 3'-RNA single cell sequencing (10x genomics).
Single-Cell Transcriptomics Identifies the Adaptation of Scart1<sup>+</sup> Vγ6<sup>+</sup> T Cells to Skin Residency as Activated Effector Cells.
Age, Specimen part, Cell line, Subject
View SamplesXylem consists of three types of cells: vessel cells, also referred to as tracheary elements (TEs), parenchyma cells, and fiber cells. TE differentiation includes two essential processes, programmed cell death (PCD) and secondary cell wall formation. These two processes are tightly coupled. However, little is known about the molecular mechanism of their gene regulation. Here, we show that VASCULAR-RELATED NAC-DOMAIN 6 (VND6), a master regulator of TEs, regulates these processes in a coordinated manner. We first identified specific genes downstream of VND6 by comparing them with those of SECONDARY WALL-ASSOCIATES NAC DOMAIN PROTEIN1 (SND1), a master regulator of xylem fiber cells, with transformed suspension culture cells in microarray experiments.
Arabidopsis VASCULAR-RELATED NAC-DOMAIN6 directly regulates the genes that govern programmed cell death and secondary wall formation during xylem differentiation.
Time
View SamplesGene expression profiling reveals a potential role of Iso towards hepatic differentiation of hAECs.
Global Gene Expression Profiling Reveals Isorhamnetin Induces Hepatic-Lineage Specific Differentiation in Human Amniotic Epithelial Cells.
Specimen part
View SamplesGene expression profiling reveals a potential role of TCQA in neuronal and pigment cell differentiation of hAECs.
Regulating cell fate of human amnion epithelial cells using natural compounds: an example of enhanced neural and pigment differentiation by 3,4,5-tri-O-caffeoylquinic acid.
Specimen part, Treatment, Time
View SamplesGene expression profiling of the effect of Cyanidine 3 glucoside treatment in hAECs.
Human Amniotic Epithelial Cells as a Tool to Investigate the Effects of Cyanidin 3-<i>O</i>-Glucoside on Cell Differentiation.
Specimen part
View SamplesOpi10 is the S. pombe homolog of human Hikeshi, which imports Hsp70s into the nucei during the heat shock.
The Schizosaccharomyces pombe Hikeshi/Opi10 protein has similar biochemical functions to its human homolog but acts in different physiological contexts.
No sample metadata fields
View SamplesIn human volunteers, we evaluated changes in gene expression profiles, immunological indices, and intestinal microbiota of blood cells in subjects consuming a S.reticulata extract. Thirty healthy Japanese males were split randomly into a group ingesting 240 mg/day of S.reticulata extract -containing tablets for 4 weeks and a control group ingesting placebo tablets. Ingestion of the S.reticulata extract improved T cell proliferation and other immunological indices, and changed intestinal microbiota, increasing Bifidobacterium and Lactobacillales and decreasing Clostridium bacteria. Expression levels of many immuno-relevant genes were altered. We have shown the S.reticulata extract to enhance human immune functions.
Improvement in Human Immune Function with Changes in Intestinal Microbiota by Salacia reticulata Extract Ingestion: A Randomized Placebo-Controlled Trial.
Specimen part, Subject, Time
View SamplesPurpose: We have succeeded in the generation and long-term expansion of SOX9-expressing CD271+PDGFRa+CD73+ chondrogenic ectomesenchymal cells from the PAX3/SOX10/FOXD3-expressing MIXL1-CD271hiPDGFRaloCD73- neural crest-like progeny of human pluripotent stem cells in a chemically defined medium supplemented with Nodal/Activin/TGFb inhibitor (SB) and FGF2 (hereafter called FSB). When “primed” with TGFb, such cells efficiently formed translucent cartilage particles, which were completely mineralized in 12 weeks in immunocompromized mice. Under the FSB condition, ectomesenchymal cells were expandable without loss of chondrogenic potential for at least 16 passages, maintained normal karyotype for at least 10 passages, which any conditions deviated from it (e.g. FGF2 alone or SB alone) failed to support. In order to address the molecular basis of such effects of FSB, a series of RNA-seq experiments were carried out. Methods: We generated and compared the transcriptome profiles of human ectomesenchymal cells expanded under FSB with those cultured under FSB first then under FGF2 alone (F). As a control, we also generated transcriptome of ectomesenchymal cells expanded from the begining under F conditions. RNA-sequencing libraries were prepared using a SureSelect Strand Specific RNA Library Preparation kit (Agilent technologies, Santa Clara, CA). Sequencing was performed on an Illumina HiSeq 1500 using a TruSeq Rapid SBS kit (Illumina, San Diego, CA) in a 50-base single-end mode. Sequenced reads were mapped against the human reference genome (GRCh37), using TopHat v2.0.12 (http://ccb.jhu.edu/software/tophat/index.shtml). Expression levels were calculated as fragments per kilobase of exon per million mapped fragments (FPKMs) using Cufflinks v2.1.1 (http://cole-trapnell-lab.github.io/cufflinks). Results: Ectomesenchymal cells maintained under FSB conditions preferentially expressed genes representing embryonic progenitors (SOX4/12, LIN28A/B, MYCN), cranial mesenchymes (ALX1/3/4) and chondroprogenitors (SOX9, COL2a1) of the neural crest origin (SOX8/9, NGFR, NES). In contrast, those cultured under FSB then F, still expressed SOX4/11/12, but lost LIN28, MYCN, ALX1/3/4, NGFR, COL2a1 expression. Interestingl it enhances expresion ofTGFß-inducible genes such as THBS1/2 and DCN and osteogenesis-related genes such as COL1a1/2 and RUNX1/2. Conclusions: The CD271+CD73+ ectomesenchymal cells accumulated under FSB conditions possess an mRNA profile of proliferating primitive neural crest/ectomesenchymal cells, although they lacked SOX10 expression, which is critical for neural and melanocytic lineage commitment. Transition from FSB to F conditions supressed the proliferation-related genes expression and enhanced the ossification/mineralization, vasculogenesis/angiogenesis, and cardiac myogenesis-related gene expression. Thus, suppression of TGFß signaling by SB does not seem to freeze the developmental stage of the hPSC-derived neural crest during expansion. Such suppression may instead simply support the high proliferative potential of the cells as well as the expression of SOX9 (and COL2a1), and thereby maintain chondrogenic activity. SOX9 expression initiated at the specification and pre-migratory stages is transient in trunk neural crest but persists in cranial neural crest. The chondrogenic CD271+CD73+ ectomesenchymal cells that maintain SOX9 transcription and translation may therefore represent proliferating cranial neural crest, with a slight commitment to non-neural lineages. Overall design: Examination of human ES-derived neural crest-like progenies expanded in 3 different culture media. Each group contains three biological replicates.
Long-term expandable SOX9+ chondrogenic ectomesenchymal cells from human pluripotent stem cells.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene expression profiling reveals epithelial mesenchymal transition (EMT) genes can selectively differentiate eribulin sensitive breast cancer cells.
Specimen part, Cell line
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