Investigation of 3D Chromatin Architecture Rewiring During Muscle Satellite Cells activation and aging [RNA-seq aging]

3D genome architecture rewiring is known to influence spatiotemporal expression of lineage-specific genes and cell fate transition during multiple lineage progression and cell differentiation. However, it is yet unknown how nuclear architecture remodels and effects transcription changes during muscle stem cell (SC) development and ageing process. Here, we comprehensively map the 3D chromatin reorganization and integrate genome topology with transcriptional and epigenetic change during muscle SC lineage development and ageing process. Rewiring of compartmentalization is most pronounced when SC become activated, while striking loss in insulation of TAD borders and chromatin looping during early activation process. Meanwhile, super-enhancer containing TAD cluster reorganize in nuclear space and orchestrate stage-specific gene expression. In depth analysis identifies and verifies cis-regulatory elements at Pax7 locus controlling the local chromatin interactions and Pax7 expression. Geriatric cells display a more prominent gain in long-range contacts and loss insulation of TAD borders. Moreover, genome compartmentalization and chromatin loop has already altered for aged SC while geriatric SC display a more prominent loss in strength of TAD borders. Together, our results implicate 3D chromatin extensively reorganizes at multiple architectural levels and underpin the transcriptome remodeling and SC behaviors during SC lineage development and SC aging. Overall design: RNA-seq was performed in freshly isolated muscle stem cell for 2 month,23-24 month and 28-32 month.