Project description:Through high-resolution single cell and genetic lineage/clonal analyses, we show an unsuspected clonal relationship between extraembryonic mesoderm and cardiac lineages. Single-cell transcriptomics and trajectory analyses uncovered two mesodermal progenitor sources contributing to left ventricle cardiomyocytes, one embryonic and the other with an extraembryonic gene expression signature. Additional lineage-tracing studies revealed that the extraembryonic-related progenitors reside at the embryonic-extraembryonic interface in gastrulating embryos, and produce distinct cell types forming the pericardium, septum transversum, epicardium, dorsolateral regions of the left ventricle and atrioventricular canal myocardium, and extraembryonic mesoderm. Clonal analyses demonstrated that these progenitors are multipotent, giving rise to not only cardiomyocytes and serosal mesothelial cell types but also, remarkably, extraembryonic mesoderm.
2021-06-08 | GSE176306 | GEO
Project description:Comparative analyses of vertebrate gut microbiomes reveal convergence between birds and bats
Project description:Cells were reprogrammed from cardiac fibroblasts to cardiomyocytes, in various conditions. These are the iCM cells (induced cardiomyocytes). There are both human and mouse arrays here, as seen below. Microarrays were used to measure the overall degree to which cellular repogramming was successful, by comparing the reprogrammed cells to reference populations of cardiomyocytes (CMs) and cardiac fibroblasts (CFs).
Project description:Direct neuronal conversion of fibroblasts from Huntington’s disease (HD) patients to striatal medium spiny neurons (MSNs) has been shown to recapitulate neurodegenerative pathology of HD. Here, we carried out comparative analyses between reprogrammed MSNs from patients at different disease stages to investigate age-associated molecular processes driving neurodegeneration. We found that neuronal death was manifested in reprogrammed MSNs from symptomatic HD patients (HD-MSNs) compared to MSNs derived from younger, pre-symptomatic patients (pre-HD-MSNs) and healthy controls. Dissecting the differential cellular state between HD-MSNs and pre-HD-MSNs by transcriptome and chromatin accessibility analyses identified miR-29b-3p, whose age-associated upregulation impairs autophagic function via human-specific targeting of STAT3. Reducing miR-29b-3p or treating with G2-115, a glibenclamide analog, increased the resilience of HD-MSNs against neurodegeneration by promoting autophagy, demonstrating that the autophagic decline during aging in HD underlies MSN degeneration and pointing to potential approaches for enhancing autophagy and resilience of MSNs against degeneration in HD.
Project description:Direct neuronal conversion of fibroblasts from Huntington’s disease (HD) patients to striatal medium spiny neurons (MSNs) has been shown to recapitulate neurodegenerative pathology of HD. Here, we carried out comparative analyses between reprogrammed MSNs from patients at different disease stages to investigate age-associated molecular processes driving neurodegeneration. We found that neuronal death was manifested in reprogrammed MSNs from symptomatic HD patients (HD-MSNs) compared to MSNs derived from younger, pre-symptomatic patients (pre-HD-MSNs) and healthy controls. Dissecting the differential cellular state between HD-MSNs and pre-HD-MSNs by transcriptome and chromatin accessibility analyses identified miR-29b-3p, whose age-associated upregulation impairs autophagic function via human-specific targeting of STAT3. Reducing miR-29b-3p or treating with G2-115, a glibenclamide analog, increased the resilience of HD-MSNs against neurodegeneration by promoting autophagy, demonstrating that the autophagic decline during aging in HD underlies MSN degeneration and pointing to potential approaches for enhancing autophagy and resilience of MSNs against degeneration in HD.
Project description:Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy primarily of the right ventricle characterized through fibrofatty replacement of cardiomyocytes. The genetic etiology in ARVC patients is most commonly caused by dominant inheritance and high genetic heterogeneity. Though histological examinations of ARVC affected human myocardium reveals fibrolipomatous replacement, the molecular mechanisms leading to loss of cardiomyocytes are largely unknown. We therefore analyzed the transcriptomes of 6 ARVC specimen derived from heart transplantation candidates and compared our findings to 6 non-failing donor hearts (NF) which could not be transplanted for technical reasons. In addition, we compared our findings to 7 hearts from patients with idiopathic dilated cardiomyopathy. From each heart left (LV) and right ventricular (RV) myocardial samples were analyzed by Affymetrix HG-U133 Plus 2.0 arrays, adding up to six sample groups. Unsupervised cluster analyses of the six sample groups revealed a clear separation of NF and cardiomyopathy samples. However, in contrast to the other samples, unsupervised cluster analyses revealed no distinct expression pattern in LV and RV samples from ARVC-hearts. We further identified differentially expressed transcripts using t-tests and found transcripts separating diseased and NF ventricular myocardium. Of note, in failing myocardium only about 15-16% of the genes are commonly regulated compared to NF samples. In addition both cardiomyopathies are clearly distinct on the transcriptome level. Comparison of the expression patterns between the failing RV and LV using a paired t-test revealed a lack of major differences between LV and RV gene expression in ARVC hearts. Microarrays were used to elucidate the differences between non-failing control hearts and those, suffering from arrhythmogenic right ventricular cardiomyopathy (ARVC).
Project description:Kashin-Beck disease (KBD) is a degenerative osteoarticular disorder, and displays the significant differences with osteoarthritis (OA) regarding the etiology and molecular changes in articular cartilage. However, the underlying dysfunctions of molecular mechanisms in KBD and OA remain unclear. Here, we performed the various genome-wide differentially methylated region analyses to reveal the distinct differentially methylated regions (DMRs) and corresponding differentially methylated genes (DMGs), and enriched functional pathways/GO terms for KBD and OA.
2020-12-03 | GSE162484 | GEO
Project description:Comparative Transcriptome Analyses of Different Orthosiphon aristatus Tissues Reveal Differentially Expressed Genes Associated with Flavonoid Biosynthesis