During mammalian kidney development, mesenchymal nephron progenitors (cap mesenchyme) differentiate into the epithelial cells that go on to form the nephron. Although differentiation of nephron progenitors is triggered by activation of Wnt/b-catenin signaling, constitutive activation of Wnt/b-catenin signaling blocks epithelialization of nephron progenitors. Full epithelialization of nephron progenitors requires transient activation of Wnt/b-catenin signaling. We performed transcriptional profiling of nephron progenitors responding to constitutive or transient activation of Wnt/b-catenin signaling.
Six2 and Wnt regulate self-renewal and commitment of nephron progenitors through shared gene regulatory networks.
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View SamplesTo assess in vitro derived podocytes, we examined the transcriptional changes during human podocyte development and applied that knowledge to pinpoint strengths and limitations of hESC-derived podocytes. Overall design: We performed transcriptionaling profiling of kidney organoids and organoid-derived MAFB-eGFP+ podocytes at various differentiation time points.
In Vivo Developmental Trajectories of Human Podocyte Inform In Vitro Differentiation of Pluripotent Stem Cell-Derived Podocytes.
Subject
View SamplesIn order to characterize and benchmark the podocytes-like cells generated through human ES cell differentiation, we generated transcriptional profiles of renal corpuscles from embryonic human kidneys using RNA-Seq. To compare, we also performed RNA-Seq of human immortalized podocyte cell lines before and after thermoswitch. Overall design: We performed RNA-Seq of poly-A selected RNA from hESC-derived kidney organoids, organoid-derived MAFB-eGFP+ podocytes at different time points, and human immortalized podocytes.
In Vivo Developmental Trajectories of Human Podocyte Inform In Vitro Differentiation of Pluripotent Stem Cell-Derived Podocytes.
Specimen part, Subject
View SamplesOur laboratory's interest is in understanding the molecular principles that underlie the regional organization of the mammalian metanephric kidney. Our goal is to generate a detailed spatial map of the cellular expression of selected regulatory genes during mammalian kidney development. The goal of this study is to identify a population of genes that are enriched in the renal vesicle (RV) and its derivatives using Wnt4 mutants.
Transcriptional profiling of Wnt4 mutant mouse kidneys identifies genes expressed during nephron formation.
Sex
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Analysis of mRNA profiles after MEK1/2 inhibition in human pancreatic cancer cell lines reveals pathways involved in drug sensitivity.
Specimen part, Cell line
View SamplesAnalysis of mRNA profiles after MEK1/2 inhibition in human pancreatic cancer cell lines reveals pathways involved in drug sensitivity.
Analysis of mRNA profiles after MEK1/2 inhibition in human pancreatic cancer cell lines reveals pathways involved in drug sensitivity.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Distinct Transcriptional Programs Underlie Sox9 Regulation of the Mammalian Chondrocyte.
Specimen part
View SamplesAnalysis of mRNA profiles after MEK1/2 inhibition in human pancreatic cancer cell lines reveals pathways involved in drug sensitivity.
Analysis of mRNA profiles after MEK1/2 inhibition in human pancreatic cancer cell lines reveals pathways involved in drug sensitivity.
Specimen part, Cell line
View SamplesMorphogenesis of cellecting duct system within developing mouse kidney is driven by growth at the tips of ureteric epithelium. To characterize the transcription program within the tip compartment, here we performed mRNA-Seq of tip cells (Wnt11RFP+;Hoxb7+ cells) and stalk cells (Wnt11RFP-;Hoxb7GFP+ cells) obtained from mouse embryonic kidney through FACS. We identified tip-specific genes from these data, and verified with in situ hybridization and followed up with mechanistic study for some of the intersting targets. Overall design: Examination of two cell types within the ureteric bud of the developing mouse kidney
Cellular heterogeneity in the ureteric progenitor niche and distinct profiles of branching morphogenesis in organ development.
Cell line, Subject
View SamplesWe compared Sox9-association at chondrocyte targets to a broad catalogue of regulatory indicators of chromatin organization and transcriptional activity to determine Sox9s direct regulatory actions in normal developing chondrocytes. Sox9-associated regions resolve into two distinct regulatory categories. Class I regions closely associate with transcriptional start sites (TSSs). Their targets reflect general regulators of basal cell activities that Sox9 engages indirectly though a likely association with the basal transcriptional complex. In contrast, Class II regions outside of the local TSS domains highlight evolutionarily conserved, active enhancers directing expression of chondrocyte specific target genes, though DNA binding of Sox9-dimers at target sites with sub-optimal binding affinity. The level of associated chondrocyte gene expression correlates with the number of enhancer modules around the target gene and grouping into super-enhancer clusters. Comparison of Sox9 programs between neural crest and mesoderm-derived chondrocytes points to similar modes of chondrocyte specification in distinct chondrocyte lineages. These data provide the first insight into mammalian Sox family actions at the genome scale in the vivo setting. The resulting enhancer sets provide a key resource for further dissection of the regulatory programs of mammalian chondrogenesis.
Distinct Transcriptional Programs Underlie Sox9 Regulation of the Mammalian Chondrocyte.
Specimen part
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