Similar Datasets
Project description:BackgroundDespite in-depth knowledge of the molecular mechanisms controlling embryonic heart development, little is known about the signals governing postnatal maturation of the human heart.MethodsSingle-nucleus RNA sequencing of 54 140 nuclei from 9 human donors was used to profile transcriptional changes in diverse cardiac cell types during maturation from fetal stages to adulthood. Bulk RNA sequencing and the Assay for Transposase-Accessible Chromatin using sequencing were used to further validate transcriptional changes and to profile alterations in the chromatin accessibility landscape in purified cardiomyocyte nuclei from 21 human donors. Functional validation studies of sex steroids implicated in cardiac maturation were performed in human pluripotent stem cell-derived cardiac organoids and mice.ResultsOur data identify the progesterone receptor as a key mediator of sex-dependent transcriptional programs during cardiomyocyte maturation. Functional validation studies in human cardiac organoids and mice demonstrate that the progesterone receptor drives sex-specific metabolic programs and maturation of cardiac contractile properties.ConclusionsThese data provide a blueprint for understanding human heart maturation in both sexes and reveal an important role for the progesterone receptor in human heart development.
| S-EPMC8055196 | biostudies-literature
Project description:The physiological adaptation of the heart to the postnatal environment is one of the most critical developmental transitions in the life of mammals. Despite in depth knowledge of the molecular mechanisms controlling embryonic heart development, little is known about the signals that govern postnatal maturation of the heart in humans. Here, we analyse the transcriptome of more than 50,000 single cells in the developing human heart from early gestation to adulthood, which enabled mapping of developmental trajectories across 7 main classes of cardiac cells over time. Striking sex-specific differences in cardiomyocyte maturation were identified and subsequently confirmed via deep RNA sequencing of purified cardiomyocytes. To identify transcriptional drivers of these changes, ATAC-seq was used to assay the open chromatin landscape, which unveiled the progesterone receptor as a key mediator of sex-dependent transcriptional changes during cardiomyocyte maturation. Functional studies in mice, as well as human pluripotent stem cell-derived cardiomyocytes and organoids, validated the progesterone receptor as a mediator of sex-specific metabolic programs and as a cardiac inotrope, consistent with a role in developmental maturation. These datasets provide a blueprint for understanding sex-specific mechanisms governing human heart development and unveil an important role for the progesterone receptor in cardiomyocyte maturation.
2021-03-22 | GSE156706 | GEO
Project description:The physiological adaptation of the heart to the postnatal environment is one of the most critical developmental transitions in the life of mammals. Despite in depth knowledge of the molecular mechanisms controlling embryonic heart development, little is known about the signals that govern postnatal maturation of the heart in humans. Here, we analyse the transcriptome of more than 50,000 single cells in the developing human heart from early gestation to adulthood, which enabled mapping of developmental trajectories across 7 main classes of cardiac cells over time. Striking sex-specific differences in cardiomyocyte maturation were identified and subsequently confirmed via deep RNA sequencing of purified cardiomyocytes. To identify transcriptional drivers of these changes, ATAC-seq was used to assay the open chromatin landscape, which unveiled the progesterone receptor as a key mediator of sex-dependent transcriptional changes during cardiomyocyte maturation. Functional studies in mice, as well as human pluripotent stem cell-derived cardiomyocytes and organoids, validated the progesterone receptor as a mediator of sex-specific metabolic programs and as a cardiac inotrope, consistent with a role in developmental maturation. These datasets provide a blueprint for understanding sex-specific mechanisms governing human heart development and unveil an important role for the progesterone receptor in cardiomyocyte maturation.
2021-03-22 | GSE156704 | GEO
Project description:The physiological adaptation of the heart to the postnatal environment is one of the most critical developmental transitions in the life of mammals. Despite in depth knowledge of the molecular mechanisms controlling embryonic heart development, little is known about the signals that govern postnatal maturation of the heart in humans. Here, we analyse the transcriptome of more than 50,000 single cells in the developing human heart from early gestation to adulthood, which enabled mapping of developmental trajectories across 7 main classes of cardiac cells over time. Striking sex-specific differences in cardiomyocyte maturation were identified and subsequently confirmed via deep RNA sequencing of purified cardiomyocytes. To identify transcriptional drivers of these changes, ATAC-seq was used to assay the open chromatin landscape, which unveiled the progesterone receptor as a key mediator of sex-dependent transcriptional changes during cardiomyocyte maturation. Functional studies in mice, as well as human pluripotent stem cell-derived cardiomyocytes and organoids, validated the progesterone receptor as a mediator of sex-specific metabolic programs and as a cardiac inotrope, consistent with a role in developmental maturation. These datasets provide a blueprint for understanding sex-specific mechanisms governing human heart development and unveil an important role for the progesterone receptor in cardiomyocyte maturation.
2021-03-22 | GSE156703 | GEO
Project description:The physiological adaptation of the heart to the postnatal environment is one of the most critical developmental transitions in the life of mammals. Despite in depth knowledge of the molecular mechanisms controlling embryonic heart development, little is known about the signals that govern postnatal maturation of the heart in humans. Here, we analyse the transcriptome of more than 50,000 single cells in the developing human heart from early gestation to adulthood, which enabled mapping of developmental trajectories across 7 main classes of cardiac cells over time. Striking sex-specific differences in cardiomyocyte maturation were identified and subsequently confirmed via deep RNA sequencing of purified cardiomyocytes. To identify transcriptional drivers of these changes, ATAC-seq was used to assay the open chromatin landscape, which unveiled the progesterone receptor as a key mediator of sex-dependent transcriptional changes during cardiomyocyte maturation. Functional studies in mice, as well as human pluripotent stem cell-derived cardiomyocytes and organoids, validated the progesterone receptor as a mediator of sex-specific metabolic programs and as a cardiac inotrope, consistent with a role in developmental maturation. These datasets provide a blueprint for understanding sex-specific mechanisms governing human heart development and unveil an important role for the progesterone receptor in cardiomyocyte maturation.
2021-03-22 | GSE156702 | GEO
Project description:The physiological adaptation of the heart to the postnatal environment is one of the most critical developmental transitions in the life of mammals. Despite in depth knowledge of the molecular mechanisms controlling embryonic heart development, little is known about the signals that govern postnatal maturation of the heart in humans. Here, we analyse the transcriptome of more than 50,000 single cells in the developing human heart from early gestation to adulthood, which enabled mapping of developmental trajectories across 7 main classes of cardiac cells over time. Striking sex-specific differences in cardiomyocyte maturation were identified and subsequently confirmed via deep RNA sequencing of purified cardiomyocytes. To identify transcriptional drivers of these changes, ATAC-seq was used to assay the open chromatin landscape, which unveiled the progesterone receptor as a key mediator of sex-dependent transcriptional changes during cardiomyocyte maturation. Functional studies in mice, as well as human pluripotent stem cell-derived cardiomyocytes and organoids, validated the progesterone receptor as a mediator of sex-specific metabolic programs and as a cardiac inotrope, consistent with a role in developmental maturation. These datasets provide a blueprint for understanding sex-specific mechanisms governing human heart development and unveil an important role for the progesterone receptor in cardiomyocyte maturation.
2021-03-22 | GSE156705 | GEO
Project description:Sex-specific control of human heart maturation by the progesterone receptor
| PRJNA658800 | ENA
Project description:Sex-specific control of human heart maturation by the progesterone receptor [bulk_RNAseq_PrKO]
| PRJNA658801 | ENA
Project description:Sex-specific control of human heart maturation by the progesterone receptor [bulk_RNAseq_human]
| PRJNA658797 | ENA
Project description:Sex-specific control of human heart maturation by the progesterone receptor [bulk_ATACseq_human]
| PRJNA658798 | ENA