Analysis of Nestin-GFP+ pericytes flow sorted from 3-day-old mouse cutaneous adipose tissue, comparing controls with wild type PDGFRa, and mutants with increased PDGFRa signaling driven by a Cre/lox-inducible D842V knockin mutation in the PDGFRa kinase domain. The control cells have adipogenic properties in vitro or when transplanted subcutaneously into recipient mice. The D842V mutant cells show altered behavior in the same assays, with poor adipogenic differentiation but a propensity to transition into profibrotic cells that secrete collagen Overall design: 3 Nes-GFP+ cells samples; 3 Nes-GFP;Nes-Cre;PDGFRa+/[S]D842V samples
PDGFRα signaling drives adipose tissue fibrosis by targeting progenitor cell plasticity.
No sample metadata fields
View SamplesNumerous studies have established a critical role for BMP signaling in skeletal development. In the developing axial skeleton, sequential SHH and BMP signals are required for specification of a chondrogenic fate in somitic tissue. A similar paradigm is thought to operate in the limb, but the signals involved are unclear. To investigate the nature of these signals we examined BMP action in mesenchymal populations derived from the early murine limb bud (~ E10.5). These populations exhibited a graded response to BMPs, in which early limb mesenchymal (EL) cells (from the distal hind limb) displayed an anti-chondrogenic response, whereas BMPs promoted chondrogenesis in older cell populations. To better understand the molecular basis of disparate BMP action in these various populations, gene expression profiling with Affymetrix microarrays was employed to identify BMP-regulated genes. These analyses showed that BMPs induced a distinct gene expression pattern in the EL cultures versus later mesenchymal limb populations (IM and LT).
Regulation of BMP-dependent chondrogenesis in early limb mesenchyme by TGFbeta signals.
Specimen part
View SamplesParathyroid hormone (PTH) plays an essential role in regulating calcium and bone homeostasis in the adult, but whether PTH is required at all for regulating fetal-placental mineral homeostasis is uncertain. To address this we treated Pth-null mice in utero with 1 nmol PTH (1-84) or saline and examined placental calcium transfer 90 minutes later. It was found that placental calcium transfer increased in Pth-null fetuses treated with PTH as compared to Pth-null fetuses treated with saline. Subsequently, to determine the effect of PTH treatment on placental gene expression, in a separate experiment, 90 minutes after the fetal injections the placentas were removed for subsequent RNA extraction and microarray analysis.
Parathyroid hormone regulates fetal-placental mineral homeostasis.
Sex, Specimen part, Treatment
View SamplesConditional deletion of Geminin from the entire hematopoietic compartment using Vav1:iCre mice led to defective hematopoiesis/dyserythropoiesis in E15.5 mouse embryos.
Geminin deletion increases the number of fetal hematopoietic stem cells by affecting the expression of key transcription factors.
Specimen part
View SamplesHelicobacter pylori clinical isolates can establish themselves in gastric epithelial stem cells and this interaction may have implications for gastric tumorigenesis. Mouse gastric epithelial progenitor cells (mGEPs) and non-progenitor gastric epithelial cells (npGECs) were infected for 24hrs with Helicobacter pylori clinical isolates Kx1 and Kx2. Kx1 was isolated from a patient with chronic atrophic gastritis (ChAG) and Kx2 from the same patient 4 years later, when he progressed to gastric adenocarcinoma.
Helicobacter pylori evolution during progression from chronic atrophic gastritis to gastric cancer and its impact on gastric stem cells.
No sample metadata fields
View SamplesThe objective of this study was to elucidate age-related differences in gene expression profiles of rhesus monkey bone marrow-derived mesenchymal stem cells (rhMSC) obtained from fetal, infant, and adult donors relevant to their growth and other properties. Although a high degree of similarity was observed in the rhMSC gene expression profiles when comparing the three age groups, significant differences were found that strongly parallel gene expression profiles of human MSC. The potential functional relevance of differential gene expression was most apparent when comparing fetal and adult rhMSC transcript profiles. Overall, the observed gene expression profiles are consistent with a loss of rhMSC pluripotency and proliferative capacity with advancing donor age. In addition, these data highlight the importance of use of non-human primates as a model system for studying the properties of human stem cells.
Age-related gene expression profiles of rhesus monkey bone marrow-derived mesenchymal stem cells.
No sample metadata fields
View SamplesComprehensive knowledge of the dynamic changes in the cardiac transciptome can inform disease mechanism. Previous transcriptome profiling studies on heart failure rely on either microarray or RNA-Seq with low coverage, leaving a large portion of the transcriptome unexplored. Additionally, previous studies only examined two end stages of the disease, onset and late-stage heart failure. Profile of the transcriptome in the middle stage of disease progression can reveal critical molecular events underlying disease transition. Towards these goals, we conducted a multi-factorial RNA-Seq experiment, comparing the dynamic changes in the transcriptome of two murine models of heart failure, pressure overload and loss of mitochondrial complex I. Our data represents the deepest transcriptome coverage to date, covering onset, progression, and late stage of the disease. We found extensive differences in the expression magnitude and dynamics of the transciptomes in different heart failure models. In addition, such differences are associated with progressive worsening of cardiac physiology. Our analysis revealed that mitochondrial dysfunction combined with stress leads to increased number of differentially expressed long intergenic noncoding RNAs, including a recently identified lincRNA that is a master regulator of the cardiac lineage during development. Overall design: Cardiac tissues were cleaned with PBS and harvested at 1, 2, 4, and 8 weeks after surgeries by freezing in liquid nitrogen. Cardiac RNA profiles of wild type (WT) and ndufs4H-/- mice after surgeries were generated by deep sequencing at 4 time points, in quadruplicate, using Illumina HiSeq2000. The three factors of the data are genetic (WT vs. ndufs4H-/-), environmental stress (trans-aortic constriction vs. Sham controls), and time (Week 1, Week 2, Week 4 and Week 8). Thus, there are 16 samples in total and each sample has 4 replicates.
Revealing Pathway Dynamics in Heart Diseases by Analyzing Multiple Differential Networks.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Peripheral Nerve Single-Cell Analysis Identifies Mesenchymal Ligands that Promote Axonal Growth.
Sex, Specimen part, Treatment
View SamplesPeripheral nerves provide a supportive growth environment for developing and regenerating axons and are essential for maintenance and repair of many non-neural tissues. This capacity has largely been ascribed to paracrine factors secreted by nerve-resident Schwann cells. Here, we used single-cell transcriptional profiling to identify ligands made by different injured rodent nerve cell types and have combined this with cell-surface mass spectrometry to computationally model potential paracrine interactions with peripheral neurons. These analyses show that peripheral nerves make many ligands predicted to act on peripheral and CNS neurons, including known and previously uncharacterized ligands. While Schwann cells are an important ligand source within injured nerves, more than half of the predicted ligands are made by nerve-resident mesenchymal cells, including the endoneurial cells most closely associated with peripheral axons. At least three of these mesenchymal ligands, ANGPT1, CCL11, and VEGFC, promote growth when locally applied on sympathetic axons. These data therefore identify an unexpected paracrine role for nerve mesenchymal cells and suggest that multiple cell types contribute to creating a highly pro-growth environment for peripheral axons.
Peripheral Nerve Single-Cell Analysis Identifies Mesenchymal Ligands that Promote Axonal Growth.
Sex, Specimen part, Treatment
View SamplesPeripheral nerves provide a supportive growth environment for developing and regenerating axons and are essential for maintenance and repair of many non-neural tissues. This capacity has largely been ascribed to paracrine factors secreted by nerve-resident Schwann cells. Here, we used single-cell transcriptional profiling to identify ligands made by different injured rodent nerve cell types and have combined this with cell-surface mass spectrometry to computationally model potential paracrine interactions with peripheral neurons. These analyses show that peripheral nerves make many ligands predicted to act on peripheral and CNS neurons, including known and previously uncharacterized ligands. While Schwann cells are an important ligand source within injured nerves, more than half of the predicted ligands are made by nerve-resident mesenchymal cells, including the endoneurial cells most closely associated with peripheral axons. At least three of these mesenchymal ligands, ANGPT1, CCL11, and VEGFC, promote growth when locally applied on sympathetic axons. These data therefore identify an unexpected paracrine role for nerve mesenchymal cells and suggest that multiple cell types contribute to creating a highly pro-growth environment for peripheral axons.
Peripheral Nerve Single-Cell Analysis Identifies Mesenchymal Ligands that Promote Axonal Growth.
Specimen part
View Samples