细菌核糖体诱导小鼠成纤维细胞的可塑性。
Bacterial Ribosomes Induce Plasticity in Mouse Adult Fibroblasts.
发表日期:2024 Jun 27
作者:
Anamika Datta, Arif Istiaq, Shigehiko Tamura, Kunimasa Ohta
来源:
Cell Death & Disease
摘要:
据报道,细菌核糖体的掺入可诱导体细胞和癌细胞的多能性,从而导致细胞谱系的转变。询问其普遍性,我们观察到细菌核糖体掺入胰蛋白酶处理的小鼠成纤维细胞(MAF)中导致核糖体诱导细胞簇(RIC)的形成,该细胞簇显示出强阳性碱性磷酸酶染色。在体外分化条件下,RICs-MAF可分化为脂肪细胞、成骨细胞和软骨细胞。此外,RICs-MAF能够分化成神经细胞。此外,RICs-MAF 表达早期衰老标志物,但没有细胞死亡。引人注目的是,这里没有观察到著名的干性标记(如 Oct4、Nanog、Sox2 等)的明显表达。后来的RNA测序数据揭示了RICs-MAF中罕见的多能性相关标记物的表达,即Dnmt3l、Sox5、Tbx3和Cdc73以及内源核糖体状态的富集。这些观察结果表明,RICs-MAF 在谱系转换过程中可能经历了非规范的多能状态。总之,我们报告了一种外切核糖体介导的 MAF 可塑状态的独特方法,该方法适合多谱系转换。
The incorporation of bacterial ribosome has been reported to induce multipotency in somatic and cancer cells which leads to the conversion of cell lineages. Queried on its universality, we observed that bacterial ribosome incorporation into trypsinized mouse adult fibroblast cells (MAF) led to the formation of ribosome-induced cell clusters (RICs) that showed strong positive alkaline phosphatase staining. Under in vitro differentiation conditions, RICs-MAF were differentiated into adipocytes, osteoblasts, and chondrocytes. In addition, RICs-MAF were able to differentiate into neural cells. Furthermore, RICs-MAF expressed early senescence markers without cell death. Strikingly, no noticeable expression of renowned stemness markers like Oct4, Nanog, Sox2, etc. was observed here. Later RNA-sequencing data revealed the expression of rare pluripotency-associated markers, i.e., Dnmt3l, Sox5, Tbx3 and Cdc73 in RICs-MAF and the enrichment of endogenous ribosomal status. These observations suggested that RICs-MAF might have experienced a non-canonical multipotent state during lineage conversion. In sum, we report a unique approach of an exo-ribosome-mediated plastic state of MAF that is amenable to multi-lineage conversion.