Pervasive RNA-binding protein enrichment on TAD boundaries regulates TAD organization DOI Creative Commons
Qiang Sun, Qin Zhou, Yulong Qiao

и другие.

Nucleic Acids Research, Год журнала: 2024, Номер 53(1)

Опубликована: Дек. 12, 2024

Mammalian genome is hierarchically organized by CTCF and cohesin through loop extrusion mechanism to facilitate the organization of topologically associating domains (TADs). Mounting evidence suggests additional factors/mechanisms exist orchestrate TAD formation maintenance. In this study, we investigate potential role RNA-binding proteins (RBPs) in organization. By integrated analyses global RBP binding 3D mapping profiles from both K562 HepG2 cells, our study unveils prevalent enrichment RBPs on boundaries define boundary-associated (baRBPs). We found that baRBP correlated with enhanced insulation strength a CTCF-independent manner. Moreover, associated nascent promoter transcription. Additional experimental testing was performed using RBFox2 as paradigm. Knockdown cells causes mild reorganization. conserved phenomenon C2C12 myoblast (MB) cells. downregulated its bound are remodeled during MB differentiation into myotubes. Finally, transcriptional inhibition indeed decreases disrupts boundary insulation. Altogether, findings demonstrate can play an active modulating co-transcriptional association synergistic actions transcripts.

Язык: Английский

Skeletal muscle stem cells modulate niche function in Duchenne muscular dystrophy mouse through YY1-CCL5 axis DOI Creative Commons
Yang Li, Chuhan Li, Qiang Sun

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 3, 2025

Abstract Adult skeletal muscle stem cells (MuSCs) are indispensable for regeneration and tightly regulated by macrophages (MPs) fibro-adipogenic progenitors (FAPs) in their niche. Deregulated MuSC/MP/FAP interactions the ensuing inflammation fibrosis hallmarks of dystrophic muscle. Here we demonstrate intrinsic deletion transcription factor Yin Yang 1 (YY1) MuSCs exacerbates pathologies altering composition heterogeneity MPs FAPs. Further analysis reveals YY1 loss induces expression immune genes MuSCs, including C-C motif chemokine ligand 5 ( Ccl5 ). Augmented CCL5 secretion promotes MP recruitment via CCL5/C-C receptor (CCR5) crosstalk, which subsequently hinders FAP clearance through elevated Transforming growth factor-β1 (TGFβ1). Maraviroc-mediated pharmacological blockade CCL5/CCR5 axis effectively mitigates dystrophy improves performance. Lastly, represses binding to its enhancer thus facilitating promoter-enhancer looping. Altogether, our study demonstrates critical role actively shaping niche provides novel insight into therapeutic intervention dystrophy.

Язык: Английский

Процитировано

1
SIRT5 safeguards against primate skeletal muscle ageing via desuccinylation of TBK1 DOI
Qian Zhao, Ying Jing, Xiaoyu Jiang

и другие.

Nature Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Март 14, 2025

Язык: Английский

Процитировано

1
Skeletal Muscle Stem Cells Modulate Niche Function in Duchenne Muscular Dystrophy through YY1-CCL5 Axis DOI Creative Commons
Yang Li, Chuhan Li, Qiang Sun

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 14, 2024

Stem cell activity is known to be tightly regulated by both intrinsic and extrinsic pathways but less about whether how stem cells modulate their niche microenvironment. Adult skeletal muscle (MuSCs) are indispensable for regeneration also macrophages (MPs) fibro-adipogenic progenitors (FAPs) in the niche. Deregulated MuSC/MP/FAP interactions ensuing inflammation fibrosis hallmarks of dystrophic muscle. Here this study we demonstrate that deletion transcription factor YY1 MuSCs exacerbates pathologies altering cellular composition heterogeneity MPs FAPs. Further analysis reveals loss induces expression immune genes MuSCs, including Ccl5. Augmented secretion CCL5 from promotes recruitment via CCL5/CCR5 mediated crosstalk, which subsequently hinders apoptosis clearance FAPs through elevated TGFβ1 accumulation. Maraviroc pharmacological blockade axis effectively mitigates dystrophy improves performance. Lastly, further represses Ccl5 directly binding its enhancer thus facilitating promoter-enhancer looping. Altogether, our has demonstrated previously unappreciated role actively shaping microenvironment secreting immunomodulatory cytokines, provided novel insight into therapeutic intervention dystrophy.

Язык: Английский

Процитировано

0
Skeletal Muscle Stem Cells Modulate Niche Function in Duchenne Muscular Dystrophy through YY1-CCL5 Axis DOI Creative Commons
Huating Wang, Yang Li, Chuhan Li

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Март 22, 2024

Abstract Stem cell activity is known to be tightly regulated by both intrinsic and extrinsic pathways but less about whether how stem cells modulate their niche microenvironment. Adult skeletal muscle (MuSCs) are indispensable for regeneration also macrophages (MPs) fibro-adipogenic progenitors (FAPs) in the niche. Deregulated MuSC/MP/FAP interactions ensuing inflammation fibrosis hallmarks of dystrophic muscle. Here this study we demonstrate that deletion transcription factor YY1 MuSCs exacerbates pathologies altering cellular composition heterogeneity MPs FAPs. Further analysis reveals loss induces expression immune genes MuSCs, including Ccl5 . Augmented secretion CCL5 from promotes recruitment via CCL5/CCR5 mediated crosstalk, which subsequently hinders apoptosis clearance FAPs through elevated TGFβ1 accumulation. Maraviroc pharmacological blockade axis effectively mitigates dystrophy improves performance. Lastly, further represses directly binding its enhancer thus facilitating promoter-enhancer looping. Altogether, our has demonstrated previously unappreciated role actively shaping microenvironment secreting immunomodulatory cytokines provided novel insight into therapeutic intervention dystrophy.

Язык: Английский

Процитировано

0
Multiomics mapping and characterization of cellular senescence in aging human muscle uncovers novel senotherapeutics for sarcopenia DOI Creative Commons
Yang Li,

Chuhan Li,

Qin Zhou

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 21, 2024

Abstract Cellular senescence is recognized as a hallmark of organismal aging but how it drives particularly in human tissues not fully understood, partly due to the complex heterogeneous nature senescence. Here this study, we leverage single-nucleus multiomics profile mononucleated cells skeletal muscle and provide first atlas. We demonstrate intra-and inter-populational transcriptomic epigenomic heterogeneity dynamics cells. also identify commonalities variations senescence-associated secretory phenotypes (SASPs) among elucidate function SASPs mediating cellular interactions niche deregulation. Furthermore, targetable SASP factors possibility using Maraviroc pharmacological senotherapeutic for treating age-associated sarcopenia muscle. Lastly, define transcription that govern state induction key underlying mechanism JUNB regulating activation senescent Altogether, our findings prevalence novel intervention sarcopenia.

Язык: Английский

Процитировано

0
Pervasive RNA-binding protein enrichment on TAD boundaries regulates TAD organization DOI Creative Commons
Qiang Sun, Qin Zhou, Yulong Qiao

и другие.

Nucleic Acids Research, Год журнала: 2024, Номер 53(1)

Опубликована: Дек. 12, 2024

Mammalian genome is hierarchically organized by CTCF and cohesin through loop extrusion mechanism to facilitate the organization of topologically associating domains (TADs). Mounting evidence suggests additional factors/mechanisms exist orchestrate TAD formation maintenance. In this study, we investigate potential role RNA-binding proteins (RBPs) in organization. By integrated analyses global RBP binding 3D mapping profiles from both K562 HepG2 cells, our study unveils prevalent enrichment RBPs on boundaries define boundary-associated (baRBPs). We found that baRBP correlated with enhanced insulation strength a CTCF-independent manner. Moreover, associated nascent promoter transcription. Additional experimental testing was performed using RBFox2 as paradigm. Knockdown cells causes mild reorganization. conserved phenomenon C2C12 myoblast (MB) cells. downregulated its bound are remodeled during MB differentiation into myotubes. Finally, transcriptional inhibition indeed decreases disrupts boundary insulation. Altogether, findings demonstrate can play an active modulating co-transcriptional association synergistic actions transcripts.

Язык: Английский

Процитировано

0