Reprogramming of human somatic cells by bacteria

Abstract

In general, it had been believed that the cell fate restriction of terminally differentiated somatic cells was irreversible. In 1952, somatic cell nuclear transfer (SCNT) was introduced to study early embryonic development in frogs. So far, various mammalian species have been successfully cloned using the SCNT technique, though its efficiency is very low. Embryonic stem (ES) cells were the first pluripotent cells to be isolated from an embryo and have a powerful potential to differentiate into more than 260 types of cells. The generation of induced pluripotent stem (iPS) cells was a breakthrough in stem cell research, and the use of these iPS cells has solved problems such as low efficiency and cell fate restriction. These cells have since been used for clinical application, disease investigation, and drug selection. As it is widely accepted that the endosymbiosis of Archaea into eukaryotic ancestors resulted in the generation of eukaryotic cells, we examined whether bacterial infection could alter host cell fate. We previously showed that when human dermal fibroblast (HDF) cells were incorporated with lactic acid bacteria (LAB), the LAB-incorporated HDF cells formed clusters and expressed a subset of common pluripotent markers. Moreover, LAB-incorporated cell clusters could differentiate into cells derived from each of the three germinal layers both in vivo and in vitro, indicating successful reprogramming of host HDF cells by LAB. In the current review, we introduce the existing examples of cellular reprogramming by bacteria and discuss their nuclear reprogramming mechanisms.

Ribosome Incorporation into Somatic Cells Promotes Lineage Transdifferentiation towards Multipotency

“…Our specific research goal is to identify cellular transdifferentiation factors in lactic acid bacteria. The cellular transdifferentiation by bacteria described previously was cell-type independent, indicating that a general underlying mechanism exists for lineage conversion by bacteria 34 . In this study, we found that ribosomes induce somatic cell transdifferentiation to restricted-multipotent cells.…”

Ribosomal protein S6 promotes stem‐like characters in glioma cells

“…Interestingly, Ito et al 11 reported that the incorporation of ribosomes or small ribosomal proteins induces stem cell‐like characters and multipotency in somatic cells. Originally, multipotency was induced by bacterial ribosomes 11,12 , however incorporation of human ribosomes induced dedifferentiation and multipotency in human skin fibroblasts 11 . Increased levels of ribosomal proteins are reportedly associated with tumorigenesis, however we investigated ribosomal proteins from the viewpoint that they induce stemness through chemoradioresistance and recurrence of GBM.…”

“…Ribosomes contain approximately 80 ribosomal proteins, which contribute to tumorigenesis, immune signaling, development, and several diseases 10 . Ribosomal incorporation into somatic cells reportedly promoted lineage trans‐differentiation toward multipotency, and these cells differentiated into different germ layer‐derived cells upon induction with respective media, such as adipocytes, osteocytes, and chondrocytes 11‐13 . These reports suggest that levels of ribosomal proteins influence the induction and maintenance of stem cell‐like features.…”

Transdifferentiation of human somatic cells by ribosome

“…). These results indicate that bacterial intrinsic factors have the potential to direct cellular reprogramming and transdifferentiation (Ito & Ohta, ).…”