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STEM CELLS

IRE1α maintains HSC stemness under ER-stress

Nature Cell Biology volume 21, pages 297–298 (2019)Cite this article

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Healthy and malignant haematopoietic stem cells (HSCs) must overcome a variety of cell intrinsic and extrinsic stresses to maintain their functionality. Now, IRE1α –XBP1 signalling is shown to protect HSCs and to promote survival of, and confer competitive advantages to, NRAS-mutated pre-leukaemic cells.

Previous work established the link between UPR signalling and HSC function, and demonstrated that the PERK branch is preferentially activated in human HSCs and leads to apoptosis under stress exposure7. Now, Liu et al. implicate activation of the IRE1α branch that, instead, protects HSCs from ER-stress-induced apoptosis6. ER stress is known to activate IRE1α through auto-phosphorylation, which in turn induces the endonuclease activity of IRE1α (ref. 3). As a result, XBP1 messenger RNA is alternatively spliced. This differentially spliced XBP1 protein isoform induces transcription of multiple genes that overcome the ER stress and prevent apoptosis3. The study by Liu et al. now highlights this ER stress rescue pathway for healthy HSCs, and may pave the way for a more detailed understanding of these mechanisms.

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Fig. 1: IRE1α signalling in cell fate determination during ER stress.

References

  1. Trumpp, A. et al. Nat. Rev. Immunol. 10, 201–209 (2010).

    Article  CAS  Google Scholar 

  2. Corazzari, M. et al. Front. Oncol. 7, 00078 (2017).

    Article  Google Scholar 

  3. Sano, R. & Reed, J. C. Biochim. Biophys. Acta. 1833, 3460–3470 (2013).

    Article  CAS  Google Scholar 

  4. Hetz, C. & Papa F. R. Mol Cell. 69, 169–181 (2018).

  5. Sigurdsson, V. & Miharada, K. Int. J. Hematol. 107, 627–633 (2018).

    Article  CAS  Google Scholar 

  6. Liu, L. et al. Nat. Cell Biol. https://doi.org/10.1038/s41556-019-0285-6 (2019).

    Article  PubMed  Google Scholar 

  7. van Galen, P. et al. Nature 510, 268–272 (2014).

    Article  Google Scholar 

  8. Chapple, R. H. et al. eLife 7, e31159 (2018).

    Article  Google Scholar 

  9. Iwawaki, T. et al. Nat. Med. 10, 98–102 (2004).

    Article  CAS  Google Scholar 

  10. Signer, R. A. et al. Nature 509, 49–54 (2014).

    Article  CAS  Google Scholar 

  11. Miharada, K. et al. Cell Rep. 7, 1381–1392 (2014).

    Article  CAS  Google Scholar 

  12. Jin, X. et al. Blood Adv. 2, 1259–1271 (2018).

    Article  Google Scholar 

  13. Bowman, R. L. et al. Cell Stem Cell 22, 157–170 (2018).

    Article  CAS  Google Scholar 

  14. Ward, A. F. et al. Blood 120, 3397–3406 (2012).

    Article  CAS  Google Scholar 

  15. Jiang, D. et al. Semin. Cancer Biol. 33, 48–56 (2015).

    Article  CAS  Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Medicine V, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany

    Marina Scheller-Wendorff & Carsten Müller-Tidow

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  1. Marina Scheller-Wendorff
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  2. Carsten Müller-Tidow
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Correspondence to Carsten Müller-Tidow.

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Competing interests

C. Müller-Tidow's leukaemia research in Investigator Initiated Trials is supported by Pfizer, Janssen and Daiichi Sankyo. Clinical trials and other research within the Department of Medicine, Hematology, Oncology and Rheumatology are supported by multiple pharmaceutical companies.

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Scheller-Wendorff, M., Müller-Tidow, C. IRE1α maintains HSC stemness under ER-stress. Nat Cell Biol 21, 297–298 (2019). https://doi.org/10.1038/s41556-019-0295-4

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