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Detecting and Modulating ER Stress to Improve Generation of Induced Pluripotent Stem Cells

Part of the Methods in Molecular Biology book series


The reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) has proven to be a powerful system creating new opportunities to interrogate molecular mechanisms controlling cell fate determination. Under standard conditions, the generation of iPSCs upon overexpression of OCT4, SOX2, KLF4, and c-MYC (OSKM) is generally slow and inefficient due to the presence of barriers that confer resistance to cell fate changes. Hyperactivated endoplasmic reticulum (ER) stress has emerged as a major reprogramming barrier that impedes the initial mesenchymal-to-epithelial transition (MET) step to form iPSCs from mesenchymal somatic cells. Here, we describe several systems to detect ER stress in the context of OSKM reprogramming and chemical interventions to modulate this process for improving iPSC formation.

Key words

Induced pluripotent stem cell Cell fate change Pluripotency Endoplasmic reticulum stress Unfolded protein response Mesenchymal-to-epithelial transition 



This research was funded by grants from the Spanish Agencia Estatal de Investigación, co-funded by the FEDER Program of the EU (BFU2016-80899-P and PID2019-105739GB-I00 to M.F. and RTI2018-096708-J-I00 to D.G.) (AEI/FEDER, UE); the Xunta de Galicia-Consellería de Cultura, Educación e Ordenación Universitaria (ED431F 2016/016 to M.F.) and the Fundación Ramón Areces (2016-PO025 to M.F.). M.F. and D.G. are recipients of a Ramón y Cajal (RYC-2014-16779) from the MINECO of Spain and Marie Skłodowska-Curie (MSCA-IF-EF-RI-895984) from the European Commission awards, respectively. A.F.-I. (MINECO, BES-2017-082007) and C.A. (Xunta de Galicia, ED481A-2020/046) are recipients of fellowships.


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Copyright information

© Springer Science+Business Media, LLC 2021

Authors and Affiliations

  1. 1.Center for Research in Molecular Medicine and Chronic Diseases (CiMUS)Universidade de Santiago de Compostela (USC)-Health Research Institute (IDIS)Santiago de CompostelaSpain
  2. 2.Department of PhysiologyUSCSantiago de CompostelaSpain
  3. 3.Department of Biochemistry and Molecular BiologyUSCSantiago de CompostelaSpain

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