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Bacterial Ribosomes Induce Plasticity in Mouse Adult Fibroblasts.

Anamika Datta1, Arif Istiaq2,3, Shigehiko Tamura4

  • 1Department of Stem Cell Biology, Graduate School of Systems Life Sciences, Kyushu University, Fukuoka 819-0395, Japan.

Cells
|July 12, 2024
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Summary

Bacterial ribosome incorporation induced multipotency in mouse adult fibroblast cells, creating ribosome-induced cell clusters (RICs). These RICs differentiated into multiple cell types, suggesting a novel non-canonical multipotent state for cell lineage conversion.

Keywords:
lineage conversionmouse adult fibroblastsmultipotencynon-canonicalplasticityribosome

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Area of Science:

  • Cell Biology
  • Stem Cell Research
  • Regenerative Medicine

Background:

  • Bacterial ribosome incorporation can induce multipotency and lineage conversion in somatic and cancer cells.
  • The universality and mechanisms of this phenomenon require further investigation.

Purpose of the Study:

  • To investigate the potential of bacterial ribosome incorporation to induce multipotency in mouse adult fibroblast cells (MAF).
  • To characterize the resulting cell clusters and their differentiation capabilities.
  • To elucidate the molecular mechanisms underlying this induced multipotent state.

Main Methods:

  • Mouse adult fibroblast cells (MAF) were treated with bacterial ribosomes.
  • Ribosome-induced cell clusters (RICs) were formed and characterized.
  • In vitro differentiation assays were performed to assess multipotency.
  • Alkaline phosphatase staining and senescence markers were analyzed.
  • RNA-sequencing was employed to identify gene expression profiles.

Main Results:

  • Bacterial ribosome incorporation into MAF generated RICs with positive alkaline phosphatase staining.
  • RICs-MAF successfully differentiated into adipocytes, osteoblasts, chondrocytes, and neural cells.
  • RICs-MAF exhibited early senescence markers without cell death.
  • No expression of canonical stemness markers (Oct4, Nanog, Sox2) was detected.
  • RNA-sequencing revealed expression of rare pluripotency markers (Dnmt3l, Sox5, Tbx3, Cdc73) and enriched ribosomal status.

Conclusions:

  • Exo-ribosome-mediated induction of a plastic state in MAF is achievable, leading to multi-lineage conversion.
  • This process represents a non-canonical multipotent state, distinct from traditional stemness.
  • This novel approach offers a unique method for cell lineage conversion and potential therapeutic applications.