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Achilles’ heel of pluripotent stem cells: genetic, genomic and epigenetic variations during prolonged culture

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Abstract

Pluripotent stem cells differentiate into almost any specialized adult cell type of an organism. PSCs can be derived either from the inner cell mass of a blastocyst—giving rise to embryonic stem cells—or after reprogramming of somatic terminally differentiated cells to obtain ES-like cells, named induced pluripotent stem cells. The potential use of these cells in the clinic, for investigating in vitro early embryonic development or for screening the effects of new drugs or xenobiotics, depends on capability to maintain their genome integrity during prolonged culture and differentiation. Both human and mouse PSCs are prone to genomic and (epi)genetic instability during in vitro culture, a feature that seriously limits their real potential use. Culture-induced variations of specific chromosomes or genes, are almost all unpredictable and, as a whole, differ among independent cell lines. They may arise at different culture passages, suggesting the absence of a safe passage number maintaining genome integrity and rendering the control of genomic stability mandatory since the very early culture passages. The present review highlights the urgency for further studies on the mechanisms involved in determining (epi)genetic and chromosome instability, exploiting the knowledge acquired earlier on other cell types.

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Authors and Affiliations

  1. Laboratorio di Biologia dello Sviluppo, Dipartimento di Biologia e Biotecnologie ‘Lazzaro Spallanzani’, Università degli Studi di Pavia, Via Ferrata 9, 27100, Pavia, Italy

    Paola Rebuzzini, Carlo Alberto Redi & Silvia Garagna

  2. Center for Health Technologies (C.H.T.), Università degli Studi di Pavia, Via Ferrata 1, Pavia, Italy

    Paola Rebuzzini, Carlo Alberto Redi & Silvia Garagna

  3. Unita’ di Anatomia, Istologia ed Embriologia, Dipartimento di Scienze Biomediche, Biotecnologiche e Traslazionali (S.BI.BI.T.), Università degli Studi di Parma, Via Volturno 39, 43100, Parma, Italy

    Maurizio Zuccotti

  4. Fondazione I.R.C.C.S. Policlinico San Matteo, Piazzale Golgi, 19, 27100, Pavia, Italy

    Carlo Alberto Redi

Authors
  1. Paola Rebuzzini
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  2. Maurizio Zuccotti
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  3. Carlo Alberto Redi
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  4. Silvia Garagna
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Corresponding authors

Correspondence to Paola Rebuzzini, Maurizio Zuccotti or Silvia Garagna.

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Rebuzzini, P., Zuccotti, M., Redi, C.A. et al. Achilles’ heel of pluripotent stem cells: genetic, genomic and epigenetic variations during prolonged culture. Cell. Mol. Life Sci. 73, 2453–2466 (2016). https://doi.org/10.1007/s00018-016-2171-8

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  • DOI: https://doi.org/10.1007/s00018-016-2171-8

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