Department of Stem Cell Biology, Graduate School of Systems Life Sciences, Kyushu University, Fukuoka 819-0395, Japan.
Department of Stem Cell Biology, Faculty of Arts and Science, Kyushu University, Fukuoka 819-0395, Japan.
Cells. 2024 Jun 27;13(13):1116. doi: 10.3390/cells13131116.
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.
细菌核糖体的掺入已被报道能诱导体细胞核和癌细胞的多能性，从而导致细胞谱系的转化。在探讨其普遍性时，我们观察到细菌核糖体掺入胰蛋白酶处理的成年小鼠成纤维细胞（MAF）中，会形成核糖体诱导的细胞簇（RICs），这些细胞簇表现出强烈的碱性磷酸酶染色阳性。在体外分化条件下，RICs-MAF 分化为脂肪细胞、成骨细胞和成软骨细胞。此外，RICs-MAF 还能分化为神经细胞。此外，RICs-MAF 表达早期衰老标志物而没有细胞死亡。值得注意的是，这里没有观察到著名的干性标志物如 Oct4、Nanog、Sox2 等的明显表达。随后的 RNA 测序数据显示，RICs-MAF 中表达了罕见的多能性相关标志物，如 Dnmt3l、Sox5、Tbx3 和 Cdc73，以及内源性核糖体状态的富集。这些观察结果表明，RICs-MAF 在谱系转化过程中可能经历了一种非典型的多能状态。总之，我们报告了一种独特的方法，通过外源性核糖体介导 MAF 的可塑性状态，使其能够进行多谱系转化。
