Three‐dimensional chromatin re‐organization during muscle stem cell aging

Abstract

Age‐related skeletal muscle atrophy or sarcopenia is a significant societal problem that is becoming amplified as the world's population continues to increase. The regeneration of damaged skeletal muscle is mediated by muscle stem cells, but in old age muscle stem cells become functionally attenuated. The molecular mechanisms that govern muscle stem cell aging encompass changes across multiple regulatory layers and are integrated by the three‐dimensional organization of the genome. To quantitatively understand how hierarchical chromatin architecture changes during muscle stem cell aging, we generated 3D chromatin conformation maps (Hi‐C) and integrated these datasets with multi‐omic (chromatin accessibility and transcriptome) profiles from bulk populations and single cells. We observed that muscle stem cells display static behavior at global scales of chromatin organization during aging and extensive rewiring of local contacts at finer scales that were associated with variations in transcription factor binding and aberrant gene expression. These data provide insights into genome topology as a regulator of molecular function in stem cell aging.

Epigenetic erosion of H4K20me1 induced by inflammation drives aged stem cell ferroptosis.

“…We hypothesized that age-associated systemic inflammation might affect the epigenome and transcriptome of MuSCs. Following our results, we performed an in-depth examination of the aged MuSC transcriptome and found that one of the most significantly enriched pathways was “Chromatin organization” ( Figure 1F ), in with our initial hypothesis and previous reports 7 , 26 . Of particular interest was the lysine methyltransferase Kmt5a, because of its crucial role in maintaining H4K20 methylation.…”

Epigenetic erosion of H4K20me1 induced by inflammation drives aged stem cell ferroptosis.

“…We hypothesized that age-associated systemic in ammation might affect the epigenome and transcriptome of MuSCs. Following our results, we performed an in-depth examination of the aged MuSC transcriptome and found that one of the most signi cantly enriched pathways was "Chromatin organization" (Figure 1F), in with our initial hypothesis and previous reports 7,26 . Of particular interest was the lysine methyltransferase Kmt5a, because of its crucial role in maintaining H4K20 methylation.…”

Nutrient-sensing growth hormone secretagogue receptor in macrophage programming and meta-inflammation

“…Monocyte/macrophage infiltration exacerbates inflammation in liver, which is positively correlated with the progression of NAFLD [ 63 ]. Liver macrophages are characterized as IMs and resident Kupffer cells (KCs) based on their gene expression profiles and developmental origins [ [64] , [65] , [66] ]. In the literature, cell expression signature of CX3CR1 + has been used as a marker of IMs, and CX3CR1 - has been used as a marker of KCs [ 67 ].…”