Cell Stem Cell 單細胞分辨率解密衰老依賴性組織再生衰退

2023年10月27日,來自中國科學院動物研究所劉光慧等研究人員合作在《細胞—干細胞》雜志上發表了標題為“ Decoding aging-dependent regenerative decline across tissues at single-cell resolution.”的研究成果,發現以單細胞分辨率解碼衰老依賴性組織再生衰退。

 

據悉,各個組織和器官的再生能力差異很大,并隨著年齡的增長而逐漸下降。

老依賴性組織再生衰退

為了解讀衰老與再生能力之間的關系,研究人員對來自年輕和衰老小鼠的八個組織的再生進行了全面的單細胞轉錄組分析。研究人員采用了多種分析模型來研究組織再生,并揭示了衰老組織再生過程減弱的復雜細胞和分子機制。具體來說,研究人員發現干細胞流動性受損血管生成不足是造成與年齡相關的再生能力下降的主要原因。

 

此外,研究人員還發現了一個獨特的Arg1+巨噬細胞亞群,它們在年輕組織中被激活,但在衰老再生組織中卻被抑制,這表明它們在再生過程中與年齡相關的免疫反應差異中發揮著重要作用。這項研究提供了一個全面的單細胞資源,可用于確定潛在的干預目標,以提高老齡人口的再生效果。

 

該研究首次在系統水平解碼了不同組織再生過程中的動態變化規律,闡明了增齡所致組織再生能力減損的細胞和分子機制,建立了再生和衰老的全新關聯,揭示了調控哺乳動物再生的潛在細胞和分子靶標,為探討多組織再生規律、剖析增齡導致的再生障礙,提供了寶貴的資源。此外,該研究鑒定出一類新型Arg1+巨噬細胞亞群,可能通過促進血管生成,參與促進組織損傷后的重塑和修復,提示靶向特定巨噬細胞有望干預衰老相關再生障礙,為發展延緩衰老的新策略提供了思路。該研究為實現組織器官修復、預防和治療衰老相關疾病奠定了重要的理論基礎

Highlights

?Aging impairs tissue regeneration across multiple organs

?Single-cell transcriptomics uncovers regeneration dynamics in young and aged tissues

?Systemic comparison reveals molecular mechanisms for this age-related decline

?These include impaired stem cell mobility, angiogenesis, and Arg1+ macrophage burst

 

Summary

Regeneration across tissues and organs exhibits significant variation throughout the body and undergoes a progressive decline with age. To decode the relationships between aging and regenerative capacity, we conducted a comprehensive single-cell transcriptome analysis of regeneration in eight tissues from young and aged mice. We employed diverse analytical models to study tissue regeneration and unveiled the intricate cellular and molecular mechanisms underlying the attenuated regenerative processes observed in aged tissues. Specifically, we identified compromised stem cell mobility and inadequate angiogenesis as prominent contributors to this age-associated decline in regenerative capacity. Moreover, we discovered a unique subset of?Arg1+?macrophages that were activated in young tissues but suppressed in aged regenerating tissues, suggesting their important role in age-related immune response disparities during regeneration. This study provides a comprehensive single-cell resource for identifying potential targets for interventions aimed at enhancing regenerative outcomes in the aging population.

 

文章來源:

Yusheng Cai, Muzhao Xiong, Zijuan Xin et al, Decoding aging-dependent regenerative decline across tissues at single-cell resolution. DOI: 10.1016/j.stem.2023.09.014,Cell Stem Cell:最新IF:25.269

 

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