The inability of the adult mammalian heart to regenerate following injury represents a major barrier in cardiovascular medicine. In contrast, the neonatal mammalian heart retains a transient capacity for regeneration, which is lost shortly after birth. Defining the molecular mechanisms that govern regenerative capacity in the neonatal period remains a central goal in cardiac biology. Here, we construct a transcriptional atlas of multiple cardiac cell populations, which enables comparative analyses of the regenerative (neonatal) versus non-regenerative (adult) state for the first time. This work provides a comprehensive transcriptional resource of multiple cardiac cell populations during cardiac development, repair and regeneration. Our findings define a transcriptional program underpinning the neonatal regenerative state and identifies an epigenetic barrier to re-induction of the regenerative program in adult cardiomyocytes. Overall design: Cardiomyocytes, fibroblasts, leukocytes and endothelial cells from infarcted and non-infarcted neonatal (P1) and adult (P56) hearts were isolated by enzymatic dissociation and FACS. RNA sequencing (RNA-seq) was performed on these cell populations to generate a transcriptomic atlas of the major cardiac cell populations during cardiac development, repair and regeneration. In addition, we surveyed the epigenetic landscape of cardiomyocytes during post-natal maturation by performing deep sequencing of accessible chromatin regions using the Assay for Transposase-Accessible Chromatin (ATAC-seq) from purified cardiomyocyte nuclei (P1, P14 and P56).
Multicellular Transcriptional Analysis of Mammalian Heart Regeneration.
Specimen part, Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A gene regulatory network anchored by LIM homeobox 1 for embryonic head development.
Specimen part
View SamplesDevelopment of the embryonic head is driven by the activity of gene regulatory networks of transcription factors. LHX1 is a homeobox transcription factor that plays an essential role in the formation of the embryonic head. The loss of Lhx1 function results in anterior truncation of the embryo caused by the disruption of morphogenetic movement of tissue precursors and the dysregulation of WNT signaling activity. Profiling the gene expression pattern in the Lhx1 mutant embryo revealed that tissues in anterior germ layers acquire posterior tissue characteristics, suggesting Lhx1 activity is required for the allocation and patterning of head precursor tissues. Here, we used LHX1 as an entry point to delineate its transcriptional targets and interactors and construct a LHX1-anchored gene regulatory network. Using a gain-of-function approach, we identified genes that immediately respond to Lhx1 activation. Meta-analysis of the datasets of LHX1-responsive genes and genes expressed in the anterior tissues of mouse embryos at head-fold stage, in conjunction with published Xenopus embryonic LHX1 (Xlim1) ChIP-seq data, has pinpointed the putative transcriptional targets of LHX1 and an array of genetic determinants functioning together in the formation of the mouse embryonic head. Overall design: Total RNA obtained from FLAG-Lhx1 and FLAG-Lhx1 mutant embryoid bodies differentiated over 2 days with or without doxycycline treatment for 16 hours. There are three replicates per condition.
A gene regulatory network anchored by LIM homeobox 1 for embryonic head development.
Specimen part, Subject
View SamplesDevelopment of the embryonic head is driven by the activity of gene regulatory networks of transcription factors. LHX1 is a homeobox transcription factor that plays an essential role in the formation of the embryonic head. The loss of Lhx1 function results in anterior truncation of the embryo caused by the disruption of morphogenetic movement of tissue precursors and the dysregulation of WNT signaling activity. Profiling the gene expression pattern in the Lhx1 mutant embryo revealed that tissues in anterior germ layers acquire posterior tissue characteristics, suggesting Lhx1 activity is required for the allocation and patterning of head precursor tissues. Here, we used LHX1 as an entry point to delineate its transcriptional targets and interactors and construct a LHX1-anchored gene regulatory network. Using a gain-of-function approach, we identified genes that immediately respond to Lhx1 activation. Meta-analysis of the datasets of LHX1-responsive genes and genes expressed in the anterior tissues of mouse embryos at head-fold stage, in conjunction with published Xenopus embryonic LHX1 (Xlim1) ChIP-seq data, has pinpointed the putative transcriptional targets of LHX1 and an array of genetic determinants functioning together in the formation of the mouse embryonic head.
A gene regulatory network anchored by LIM homeobox 1 for embryonic head development.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcriptional shift identifies a set of genes driving breast cancer chemoresistance.
Sex, Age, Specimen part, Treatment
View SamplesThe aim of this study was to compare the gene expression profile changes breast tumors after the treatment with Anthracyclines and Taxanes. To this end, an oligonucleotide microarray was performed (Affymetrixs HG-U133 Plus 2.0 array). This gene expression study was carried out on the biopsied tumor samples previous being treated with chemotherapy, and subsequently compared with themselves once treatment schedule ended. The post-chemotherapy biopsy was obtained from the surgical piece. The goal of this study was the finding of several genes related to apoptosis, proliferation, differentiation, survival and transformation-related genes and correlating their differences in expression with the degree of response to chemotherapy, determined by the Miller and Payne histological grading system.
Transcriptional shift identifies a set of genes driving breast cancer chemoresistance.
Sex, Age, Specimen part, Treatment
View SamplesThe aim of this study was to compare the gene expression profile changes breast tumors after the treatment with Anthracyclines and Taxanes. To this end, an oligonucleotide microarray was performed (Affymetrixs HG-U133 Plus 2.0 array). This gene expression study was carried out on the biopsied tumor samples previous being treated with chemotherapy, and subsequently compared with themselves once treatment schedule ended. The post-chemotherapy biopsy was obtained from the surgical piece. The goal of this study was the finding of several genes related to apoptosis, proliferation, differentiation, survival and transformation-related genes and correlating their differences in expression with the degree of response to chemotherapy, determined by the Miller and Payne histological grading system.
Transcriptional shift identifies a set of genes driving breast cancer chemoresistance.
Sex, Age, Specimen part, Treatment
View SamplesThe aim of this study was to compare the gene expression profile changes breast tumors after the treatment with Anthracyclines and Taxanes. To this end, an oligonucleotide microarray was performed (Affymetrixs HG-U133 Plus 2.0 array). This gene expression study was carried out on the biopsied tumor samples previous being treated with chemotherapy, and subsequently compared with themselves once treatment schedule ended. The post-chemotherapy biopsy was obtained from the surgical piece. The goal of this study was the finding of several genes related to apoptosis, proliferation, differentiation, survival and transformation-related genes and correlating their differences in expression with the degree of response to chemotherapy, determined by the Miller and Payne histological grading system.
Transcriptional shift identifies a set of genes driving breast cancer chemoresistance.
Sex, Age, Specimen part, Treatment
View SamplesThe aim of this study was to compare the gene expression profile changes of DMBA-induced rat breast tumors after treatment with hydroxytyrosol (a natural compound from virgin olive oil). To this end, a cDNA microarray experiment was performed (Affymetrixs Rat Genome 230 2.0 array). This gene expression study was carried out on the tumor biopsy samples prior to hydroxytyrosol treatment, and compared with matched tumor biopsy samples after completion of the hydroxytyrosol treatment schedule. The result of this study was the identification of several genes related to apoptosis, cell cycle arrest, proliferation, differentiation, survival and transformation-related genes.
Hydroxytyrosol inhibits growth and cell proliferation and promotes high expression of sfrp4 in rat mammary tumours.
Sex, Age, Specimen part, Treatment
View SamplesThe aim of this study was to compare the gene expression profile changes of DMBA-induced rat breast tumors after treatment with adriamycin. To this end, a cDNA microarray was performed (Affymetrixs Rat Genome 230 2.0 array). This gene expression study was carried out on the tumor biopsy samples prior to adriamycin treatment, and compared with matched tumor biopsy samples after completion of the adriamycin treatment schedule.
Hydroxytyrosol inhibits growth and cell proliferation and promotes high expression of sfrp4 in rat mammary tumours.
Sex, Age, Specimen part, Treatment
View Samples