Mesenchymal stem cells generate distinct functional hybrids in vitro via cell fusion or entosis.
Homotypic and heterotypic cell-to-cell fusion are key processes during development and tissue regeneration. Nevertheless, aberrant cell fusion can contribute to tumour initiation and metastasis. Additionally, a form of cell-in-cell structure called entosis has been observed in several human tumours. Here we investigate cell-to-cell interaction between mouse mesenchymal stem cells (MSCs) and embryonic stem cells (ESCs). MSCs represent an important source of adult stem cells since they have great potential for regenerative medicine, even though they are also involved in cancer progression. We report that MSCs can either fuse forming heterokaryons, or be invaded by ESCs through entosis. While entosis-derived hybrids never share their genomes and induce degradation of the target cell, fusion-derived hybrids can convert into synkaryons. Importantly we show that hetero-to-synkaryon transition occurs through cell division and not by nuclear membrane fusion. Additionally, we also observe that the ROCK-actin/myosin pathway is required for both fusion and entosis in ESCs but only for entosis in MSCs. Overall, we show that MSCs can undergo fusion or entosis in culture by generating distinct functional cellular entities. These two processes are profoundly different and their outcomes should be considered given the beneficial or possible detrimental effects of MSC-based therapeutic applications.
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Spain.
Francesco
F
Sottile
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Spain.
Francesco
F
Aulicino
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Spain.
Ilda
I
Theka
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Spain.|ICREA, Pg. Lluís Companys 23, 08010 Barcelona, Spain.
Maria Pia
MP
Cosma
D000199:Actins / Q000378:metabolism; D000818:Animals; D002459:Cell Fusion; D018920:Coculture Techniques; D057691:Entosis; D006822:Hybrid Cells / Q000166:cytology* / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
D000199:Actins; D054460:rho-Associated Kinases; D009218:Myosins