Hematopoietic stem cells (HSCs) undergo profound epigenetic remodeling during aging, driving myeloid bias and reduced lymphoid potential.
Two key regulators — KDR (VEGFR2, marking long-term HSCs) and PU.1 (SPI1, myeloid master regulator) —
show dramatically altered chromatin accessibility and expression with age. This viewer visualizes epigenomic changes at these critical loci.
Differentially Accessible Peaks
2,847
ATAC-seq, Young vs Old HSCs (FDR < 0.05)
Differentially Methylated Regions
1,423
WGBS, Δβ > 0.2, 834 hyper / 589 hypo
DEGs at KDR/PU.1 Loci
156
RNA-seq, |log2FC| > 1, adj.p < 0.01
🧬 Chromatin Accessibility Change
📊 Histone Mark Distribution
🔬 Age-Associated Epigenetic Drift
📋 Key Findings
1. KDR promoter loses H3K4me3 and gains H3K27me3 with age → transcriptional silencing
2. PU.1 enhancers gain accessibility in old HSCs → myeloid bias amplification
3. Global DNA methylation entropy increases 34% in old HSCs
4. Bivalent chromatin domains at lineage genes resolve toward myeloid in old HSCs
5. CTCF binding at TAD boundaries near KDR weakens → altered 3D chromatin topology
ATAC-seq and ChIP-seq tracks showing chromatin accessibility and histone modifications at the KDR and PU.1 loci
in young (2–4 month) and old (22–24 month) mouse HSCs. Peak heights represent normalized signal intensity.
🧬 KDR Locus — Chr5: 75,890,000–75,960,000
🧬 PU.1 (SPI1) Locus — Chr11: 68,135,000–68,185,000
📊 Peak Count by Histone Mark
📈 Signal-to-Noise Ratio
RNA-seq differential expression analysis at KDR/PU.1 regulatory network genes.
Bar lengths represent relative expression (TPM), comparing Young and Old HSCs.
🔵 KDR Network — Expression Changes
🔴 PU.1 Network — Expression Changes
🌋 Volcano Plot — All Differentially Expressed Genes
📊 Lineage Bias Score
🧮 Top GO Terms (Up in Old)
Whole-genome bisulfite sequencing (WGBS) reveals DNA methylation changes at CpG sites across the KDR and PU.1 loci.
Heatmaps show β-values (0 = unmethylated, 1 = fully methylated). Old HSCs show increased methylation entropy.
🔵 KDR Promoter CpG Methylation
🔴 PU.1 Enhancer CpG Methylation
📊 Methylation at Genomic Features
📈 Entropy Change with Age
🧬 Epigenetic Clock CpG Sites at HSC Loci
Interactive pathway map showing the KDR and PU.1 signaling networks in HSC aging.
Click nodes to highlight connections. Blue = reduced with age, Red = increased with age.
🗺️ KDR / PU.1 Aging Pathway Network
📊 Pathway Enrichment (Old vs Young)
🔗 Transcription Factor Binding