Similar Datasets
Project description:RNA sequencing from mouse hearts or PDGFR⍺ cardiac fibroblasts along time of aging.
2020-11-10 | GSE161078 | GEO
Project description:Cardiac fibrosis is a pathophysiologic hallmark of the aging heart. In the uninjured heart, cardiac fibroblasts exist in the quiescent state, but little is known about how proliferation rates and fibroblast transcriptional programs change throughout the lifespan of the organism from the immediate postnatal period to adult life and old age. Using EdU pulse labeling, we demonstrate that more than 50% of cardiac fibroblasts are actively proliferating in the first day of post-natal life. However, within 4 weeks of birth in the juvenile animal, only 10% of cardiac fibroblasts are proliferating. By early adulthood, the fraction of proliferating cardiac fibroblasts further decreases to approximately 2%, where it so remains throughout the rest of the organism’s life span. Examination of absolute cardiac fibroblast numbers demonstrated concordance with age related changes in fibroblast proliferation with no significant differences in absolute cardiac fibroblast numbers between animals 14 weeks and 1.5 years of age. We demonstrate that the maximal changes in cardiac fibroblast transcriptional programs and in particular collagen expression occur within the first weeks of life from the immediate postnatal to the juvenile period. We show that even though the aging heart exhibits an increase in the total amount of accumulated collagen, transcription of various collagens and ECM genes both in the heart and cardiac fibroblast is maximal in the newly born and juvenile animal and decreases with organismal aging. Examination of DNA methylation changes both in the heart and in cardiac fibroblasts did not demonstrate significant changes in differentially methylated regions between young and old mice. Our observations demonstrate that cardiac fibroblasts attain a stable proliferation rate and transcriptional program early in the life span of the organism and suggest a model of cardiac aging where phenotypic changes in the aging heart are not directly attributable to changes in proliferation rate or altered collagen expression in cardiac fibroblasts.
2020-10-26 | GSE160074 | GEO
Project description:Cardiac fibrosis is a pathophysiologic hallmark of the aging heart, but little is known about how fibroblast proliferation and transcriptional programs change throughout the life span of the organism. Using EdU pulse labeling, we demonstrated that more than 50% of cardiac fibroblasts were actively proliferating in the first day of postnatal life. However, by 4 weeks, only 10% of cardiac fibroblasts were proliferating. By early adulthood, the fraction of proliferating cardiac fibroblasts further decreased to approximately 2%, where it remained throughout the rest of the organism's life. We observed that maximal changes in cardiac fibroblast transcriptional programs and, in particular, collagen and ECM gene expression both in the heart and cardiac fibroblast were maximal in the newly born and juvenile animal and decreased with organismal aging. Examination of DNA methylation changes both in the heart and in cardiac fibroblasts did not demonstrate significant changes in differentially methylated regions between young and old mice. Our observations demonstrate that cardiac fibroblasts attain a stable proliferation rate and transcriptional program early in the life span of the organism and suggest that phenotypic changes in the aging heart are not directly attributable to changes in proliferation rate or altered collagen expression in cardiac fibroblasts.
| S-EPMC7819745 | biostudies-literature
Project description:Cardiac fibroblast proliferation rates and collagen expression mature early in life and do not change with advancing age
| PRJNA675487 | ENA
Project description:Cardiac fibroblast proliferation rates and collagen expression mature early in life and do not change with advancing age [RNA-Seq]
| PRJNA675497 | ENA
Project description:Cardiac fibroblast proliferation rates and collagen expression mature early in life and do not change with advancing age [Bisulfite-Seq]
| PRJNA671732 | ENA
Project description:Previous studies have implicated the attractive and promising role of miR-590-3p to restore the cardiac function following myocardial infarction (MI). However, the molecular mechanisms for how miR-590-3p involves in cardiac fibrosis remain largely unexplored. Using human cardiac fibroblasts (HCFs) as the cellular model, luciferase report assay, mutation, EdU assay and transwell migration assay were applied to investigate the biological effects of miR-590-3p on the proliferation, differentiation, migration and collagen synthesis of cardiac fibroblasts. We found that miR-590-3p significantly suppressed cell proliferation and migration of HCFs. The mRNA and protein expression levels of α-SMA, Col1A1 and Col3A were significantly decreased by miR-590-3p. Moreover, miR-590-3p directly targeted at the 3'UTR of ZEB1 to repress the translation of ZEB1. Interfering with the expression of ZEB1 significantly decreased the cell proliferation, migration activity, mRNA and protein expressions of α-SMA, Col1A1 and Col3A. Furthermore, the expressions of miR-590-3p and ZEB1 were identified in infarct area of MI model in pigs. Collectively, miR-590-3p suppresses the cell proliferation, differentiation, migration and collagen synthesis of cardiac fibroblasts by targeting ZEB1. These works will provide useful biological information for future studies on potential roles of miR-590-3p as the therapeutic target to recover cardiac function following MI.
| S-EPMC6933374 | biostudies-literature
Project description:The incidence of left ventricular diastolic dysfunction significantly increases in postmenopausal women suggesting the association between estrogen loss and diastolic dysfunction. The in vivo activation of G protein-coupled estrogen receptor (GPR30) attenuates the adverse effects of estrogen loss on cardiac fibrosis and diastolic dysfunction in mRen2.Lewis rats. This study was designed to address the effects of GPR30 on cardiac fibroblast proliferation in rats. The expression of GPR30 in cardiac fibroblasts isolated from adult Sprague-Dawley rats was confirmed by RT-PCR, Western blot analysis, and immunofluorescence staining. Results from BrdU incorporation assays, cell counting, carboxyfluorescein diacetate succinimidyl ester labeling in conjunction with flow cytometry, and Ki-67 staining showed that treatment with G1, a specific agonist of GPR30, inhibited cardiac fibroblast proliferation in a dose-dependent manner, which was associated with decreases in CDK1 and cyclin B1 protein expressions. In the GPR30-KO cells, BrdU incorporation, and CDK1 and cyclin B1 expressions significantly increased when compared to GPR30-intact cells. G1 had no effect on BrdU incorporation, CDK1 and cyclin B1 mRNA levels in GPR30-KO cells. In vivo studies showed increases in CDK1 and cyclin B1 mRNA levels, Ki-67-positive cells, and the immunohistochemistry staining of vimentin, a fibroblast marker, in the left ventricles from ovariectomized mRen2.Lewis rats versus hearts from ovary-intact littermates; 2 weeks of G1 treatment attenuated these adverse effects of estrogen loss. This study demonstrates that GPR30 is expressed in rat cardiac fibroblasts, and activation of GPR30 limits proliferation of these cells likely via suppression of the cell cycle proteins, cyclin B1, and CDK1.
| S-EPMC4449333 | biostudies-literature
Project description:Cardiovascular disease is a common diabetic complication that can arise when cardiac fibroblasts transition into myofibroblasts. Myofibroblast transition can be induced by advanced glycated end products (AGEs) present in the extracellular matrix (ECM) activating RAGE (receptor for advanced glycated end products) to elicit intracellular signaling. The levels of AGEs are higher under diabetic conditions due to the hyperglycemic conditions present in diabetics. AGE/RAGE signaling has been shown to alter protein expression and ROS production in cardiac fibroblasts, resulting in changes in cellular function, such as migration and contraction. Recently, a small GTPase, Rap1a, has been identified to overlap the AGE/RAGE signaling cascade and mediate changes in protein expression. While Rap1a has been shown to impact AGE/RAGE-induced protein expression, there are currently no data examining the impact Rap1a has on AGE/RAGE-induced cardiac fibroblast function. Therefore, we aimed to determine the impact of Rap1a on AGE/RAGE-mediated cardiac fibroblast contraction, as well as the influence isolated diabetic ECM has on facilitating these effects. In order to address this idea, genetically different cardiac fibroblasts were embedded in 3D collagen matrices consisting of collagen isolated from either non-diabetic of diabetic mice. Fibroblasts were treated with EPAC and/or exogenous AGEs, which was followed by assessment of matrix contraction, protein expression (α-SMA, SOD-1, and SOD-2), and hydrogen peroxide production. The results showed Rap1a overlaps the AGE/RAGE cascade to increase the myofibroblast population and generation of ROS production. The increase in myofibroblasts and oxidative stress appeared to contribute to increased matrix contraction, which was further exacerbated by diabetic conditions. Based off these results, we determined that Rap1a was essential in mediating the response of cardiac fibroblasts to AGEs within diabetic collagen.
| S-EPMC8224555 | biostudies-literature
Project description:Age-related deficits in the immune system have been associated with an increased incidence of infections, autoimmune diseases, and cancer. Human B cell populations change quantitatively and qualitatively in the elderly. However, the function of human B-1 cells, which play critical anti-microbial and housekeeping roles, have not been studied in the older age population. In the present work, we analyzed how the frequency, function and repertoire of human peripheral blood B-1 cells (CD19+CD20+CD27+CD38low/intCD43+) change with age. Our results show that not only the percentage of B-1 cells but also their ability to spontaneously secrete IgM decreased with age. Further, expression levels of the transcription factors XBP-1 and Blimp-1 were significantly lower, while PAX-5, characteristic of non-secreting B cells, was significantly higher, in healthy donors over 65 years (old) as compared to healthy donors between 20 and 45 years (young). To further characterize the B-1 cell population in older individuals, we performed single cell sequencing analysis of IgM heavy chains from healthy young and old donors. We found reduced repertoire diversity of IgM antibodies in B-1 cells from older donors as well as differences in usage of certain VH and DH specific genes, as compared to younger. Overall, our results show impairment of the human B-1 cell population with advancing age, which might impact the quality of life and onset of disease within the elderly population.
| S-EPMC6433875 | biostudies-literature