Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Loss of Nuclear Receptor Nr4a3 Alleviates Cellular Senescence to Promote Adult Direct Cardiac Reprogramming (ATAC-Seq)

ABSTRACT: Direct cardiac reprogramming of fibroblast to cardiomyocytes represents a potential means of restoring cardiac function following injury. However, aged and adult fibroblast are less efficient for reprogramming compared with neonatal fibroblast. In this study, through the joint analysis of RNAseq and ATACseq, we found that compared with Neo-iCM, cardiac related features were down-regulated with aging, while fibrosis and SASP related genes were significantly up-regulated with aging. Single-cell transcriptomics reveals a bifurcated trajectory of aged iCM reprogramming. Then, we screened 51 transcriptomic and epigenomic regulators of the barriers to aged-iCM reprogramming and found that Nuclear receptor subfamily 4 group A member 3 (Nr4a3), an pro-inflammatory transcription factor, induced cellular senescence to inhibit direct reprogramming during aging. Mechanistically, knockdown of Nr4a3 enhanced direct cardiac reprogramming by promoting cardiac gene programs and inhibiting fibrosis pathway and secretes SASP. In addition, knockdown of Nr4a3 promoted human reprogramming in primary ventricular human cardiac fibroblasts (HCFs) and improved heart function after MI.

ORGANISM(S): Mus musculus

PROVIDER: GSE267447 | GEO | 2025/08/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Loss of Nuclear Receptor Nr4a3 Alleviates Cellular Senescence to Promote Adult Direct Cardiac Reprogramming (RNA-Seq)

Project description:Direct cardiac reprogramming of fibroblast to cardiomyocytes represents a potential means of restoring cardiac function following injury. However, aged and adult fibroblast are less efficient for reprogramming compared with neonatal fibroblast. In this study, through the joint analysis of RNAseq and ATACseq, we found that compared with Neo-iCM, cardiac related features were down-regulated with aging, while fibrosis and SASP related genes were significantly up-regulated with aging. Single-cell transcriptomics reveals a bifurcated trajectory of aged iCM reprogramming. Then, we screened 51 transcriptomic and epigenomic regulators of the barriers to aged-iCM reprogramming and found that Nuclear receptor subfamily 4 group A member 3 (Nr4a3), an pro-inflammatory transcription factor, induced cellular senescence to inhibit direct reprogramming during aging. Mechanistically, knockdown of Nr4a3 enhanced direct cardiac reprogramming by promoting cardiac gene programs and inhibiting fibrosis pathway and secretes SASP. In addition, knockdown of Nr4a3 promoted human reprogramming in primary ventricular human cardiac fibroblasts (HCFs) and improved heart function after MI.

2025-08-22 | GSE267450 | GEO

Loss of Nuclear Receptor Nr4a3 Alleviates Cellular Senescence to Promote Adult Direct Cardiac Reprogramming (CUT&Tag)

2025-08-22 | GSE267448 | GEO

Gene expression profile of human cardiac fibroblasts (HCFs), induced cardiomyocytes (iCMs), and heart

Project description:Global gene expression profile of total 24460 probes in the iCMs. The gene expression shifts from a fibroblast state toward a cardiac-like phenotype by Gata4/Mef2c/Tbx5/Mesp1/Myocd (GMTMM) or GMTMM/miR-133 transduction at 7 days after transduction. MiR-133 silenced fibroblast signatures in parallel with cardiac gene activation, and Snai1 overexpression inhibited the effects of miR-133-mediated cardiac reprogramming. HCFs were used for negative control, human heart tissue for positive control. Gene expression profiles were compared among HCFs, iCMs and heart. 24460 probes were analyzed in each experiment.

2014-07-03 | E-GEOD-56874 | biostudies-arrayexpress

The translational landscape of direct cardiac reprogramming reveals a role of Ybx1 in repressing cardiac fate acquisition [scRNA-seq and scATAC-seq]

Project description:Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds great promise for heart regeneration. Although great progress has been made in understanding the transcriptional and epigenetic mechanisms of iCM reprogramming, its translational regulation remains largely unexplored. Here we characterized the translational landscape of iCM reprogramming using integrative ribosome and transcriptomic profiling, and showed extensive translatome re-patterning during fibroblast conversion into iCM. Loss of function screening for translational regulators uncovered Ybx1 as a critical barrier to iCM induction. Knockdown of Ybx1 dramatically improved the efficiency and quality of iCM reprogramming. Mechanistically, Ybx1 directly bound the transcripts of Srf and Baf60c, both of which mediated, at least partially, the repressive effect of Ybx1 on iCM generation.and Depletion of Ybx1 de-repressed the translation of its targets including SRF and Baf60c. Interestingly, upon removing Ybx1, Tbx5 alone could reprogram fibroblasts into iCMs that exhibit classic iCM molecular features and reprogramming trajectories revealed by our single cell dual-omics. In sum, we presented here a global view of translatome dynamics of cardiac reprogramming and identified a novel translational barrier, Ybx1, to iCM generation. Removing this barrier allowed the single factor mediated iCM reprogramming.

2023-08-24 | GSE196125 | GEO

The translational landscape of direct cardiac reprogramming reveals a role of Ybx1 in repressing cardiac fate acquisition [Ribo-seq and RNA-seq]

2023-08-24 | GSE196124 | GEO

The translational landscape of direct cardiac reprogramming reveals a role of Ybx1 in repressing cardiac fate acquisition [scRNA-seq]

2023-08-24 | GSE237267 | GEO

Decoding Aging in the Heart via Single Cell Dual Omics of Non-Cardiomyocytes (scATAC-Seq)

Project description:(scRNA and scATAC) in profiling non-myocytes (non-CMs) from young, middle-aged, and elderly mice. Non-CMs, vital in heart development, physiology, and pathology, are understudied compared to cardiomyocytes. Our analysis revealed aging response heterogeneity and its dynamics over time among non-CM cell types. Immune cells, notably macrophages and neutrophils, showed significant aging alterations, while endothelial cells displayed moderate changes. We identified distinct aging signatures within the cell type, including differential gene expression and transcription factor activity, along with motif variation. Sub-cluster analysis revealed intra-cell type heterogeneity, characterized by diverse aging patterns. The senescence-associated secretory phenotype (SASP) emerged as a key aging-related phenotype. Moreover, aging significantly influenced cell-cell communication, especially impacting a fibroblast sub-cluster with high expression of Erbb4. This study elucidates the complex cellular and molecular landscape of cardiac aging in non-CMs, highlighting their importance in cardiac aging and offering guidance for future potential therapeutic avenues to treat aging-related heart diseases.

2024-11-01 | GSE277701 | GEO

Decoding Aging in the Heart via Single Cell Dual Omics of Non-Cardiomyocytes (scRNA-Seq)

2024-11-01 | GSE277700 | GEO

Hybrid hydrogel-extracellular matrix scaffolds identify distinct biochemical and mechanical signatures of cardiac ageing

Project description:Extracellular matrix remodeling of cardiac tissue is a key contributor to age-related cardiovascular disease and dysfunction. Such remodeling is multifaceted including changes to biochemical composition, architecture, and mechanics, clouding our understanding of how and which extracellular matrix properties contribute to a dysfunctional state. Here we describe a decellularized extracellular matrix-synthetic hydrogel hybrid that independently presents two distinct matrix properties, ligand presentation and stiffness, to cultured cells in vitro, allowing for the identification of their specific roles in cardiac aging. The hybrid scaffold maintains native matrix composition and organization of young or aged murine cardiac tissue, while its mechanical properties can be independently tuned to mimic young or aged tissue stiffness. Seeding these scaffolds with murine primary cardiac fibroblasts, we identify distinct age- and matrix-dependent mechanisms of cardiac fibroblast activation, matrix remodeling, and senescence. Importantly, we show that ligand presentation of young extracellular matrix can outweigh profibrotic stiffness cues typically present in aged extracellular matrix in maintaining or driving cardiac fibroblast quiescence. Ultimately, these tunable scaffolds can enable the discovery of specific extracellular targets to prevent aging dysfunction and promote rejuvenation.

2025-06-07 | PXD060864 | Pride

Enhanced cardiac reprogramming by Inhibition of cyclooxygenase-2/prostaglandin E2/prostaglandin E receptor 4 signaling

Project description:Direct cardiac reprogramming from fibroblasts can be a promising approach for disease modeling, drug screening, and cardiac regeneration in pediatric and adult patients. However, postnatal and adult fibroblasts are less efficient for reprogramming compared with embryonic fibroblasts, and barriers to cardiac reprogramming associated with aging remain undetermined. In this study, we screened 8,400 chemical compounds, and found that diclofenac sodium (diclofenac), a non-steroidal anti-inflammatory drug, greatly enhanced cardiac reprogramming in combination with Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Hand2. Intriguingly, diclofenac promoted cardiac reprogramming in mouse postnatal and adult tail-tip fibroblasts (TTFs), but not in mouse embryonic fibroblasts (MEFs). Mechanistically, diclofenac enhanced cardiac reprogramming by inhibiting cyclooxygenase-2, prostaglandin E2/prostaglandin E receptor 4, cyclic AMP/protein kinase A, and interleukin 1b pathway, silencing inflammatory and fibroblast programs, which were activated in postnatal and adult TTFs. Thus, anti-inflammation can be a new target for cardiac reprogramming associated with aging.

2019-02-20 | GSE116223 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data