Cited by 363Hematopoietic Stem Cell TransplantationEndoplasmic Reticulum Stress and DiseaseHeat shock proteins research

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The unfolded protein response governs integrity of the haematopoietic stem-cell pool during stress

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van Galen, Peter, Kreso, Antonija, Mbong, Nathan, Kent, David G., Fitzmaurice, Timothy, Chambers, Joseph E., Xie, Stephanie, Laurenti, Elisa, Hermans, Karin, Eppert, Kolja, Marciniak, Stefan J., Goodall, Jane C., Green, Anthony R., Wouters, Bradly G., Wienholds, Erno, Dick, John E.·2014·Nature

DOI 10.1038/nature13228

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Abstract

The blood system is sustained by a pool of haematopoietic stem cells (HSCs) that are long-lived due to their capacity for self-renewal. A consequence of longevity is exposure to stress stimuli including reactive oxygen species (ROS), nutrient fluctuation and DNA damage. Damage that occurs within stressed HSCs must be tightly controlled to prevent either loss of function or the clonal persistence of oncogenic mutations that increase the risk of leukaemogenesis. Despite the importance of maintaining cell integrity throughout life, how the HSC pool achieves this and how individual HSCs respond to stress remain poorly understood. Many sources of stress cause misfolded protein accumulation in the endoplasmic reticulum (ER), and subsequent activation of the unfolded protein response (UPR) enables the cell to either resolve stress or initiate apoptosis. Here we show that human HSCs are predisposed to apoptosis through strong activation of the PERK branch of the UPR after ER stress, whereas closely related progenitors exhibit an adaptive response leading to their survival. Enhanced ER protein folding by overexpression of the co-chaperone ERDJ4 (also called DNAJB9) increases HSC repopulation capacity in xenograft assays, linking the UPR to HSC function. Because the UPR is a focal point where different sources of stress converge, our study provides a framework for understanding how stress signalling is coordinated within tissue hierarchies and integrated with stemness. Broadly, these findings reveal that the HSC pool maintains clonal integrity by clearance of individual HSCs after stress to prevent propagation of damaged stem cells.

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Maere, S., Heymans, K., & Kuiper, M. T. R. (2005) · Computer applications in the biosciences · doi:10.1093/bioinformatics/bti551 · Cited by 4,163
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Harding, H. P., Zhang, Y., & Ron, D. (1999) · Nature · doi:10.1038/16729 · Cited by 3,310
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Circadian- and UPR-dependent control of CPEB4 mediates a translational response to counteract hepatic steatosis under ER stress
Maillo, C., Martín, J., Sebastián, D., Hernández-Alvarez, M., García-Rocha, M., Reina, O., Zorzano, A., Fernandez, M., & Méndez, R. (2017) · Nature Cell Biology · doi:10.1038/ncb3461 · Cited by 82
Decreased MORF leads to prolonged endoplasmic reticulum stress in periodontitis-associated chronic inflammation
Xue, P., Li, B., An, Y., Sun, J., He, X., Hou, R., Dong, G., Fei, D., Jin, F., Wang, Q., et al. (2016) · Cell Death and Differentiation · doi:10.1038/cdd.2016.74 · Cited by 82
The saturated fatty acid, palmitic acid, induces anxiety-like behavior in mice
Moon, M. L., Joesting, J. J., Lawson, M. A., Chiu, G. S., Blevins, N. A., Kwakwa, K. A., & Freund, G. G. (2014) · Metabolism · doi:10.1016/j.metabol.2014.06.002 · Cited by 87
ATF4 plays a pivotal role in the development of functional hematopoietic stem cells in mouse fetal liver
Zhao, Y., Zhou, J. R., Liu, D., Dong, F., Cheng, H., Wang, W., Pang, Y., Wang, Y., Mu, X., Ni, Y., et al. (2015) · Blood · doi:10.1182/blood-2015-03-633354 · Cited by 82
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Wielenga, M. C. B., Çolak, S., Heijmans, J., de Jeude, J. F. V. L., Rodermond, H. M., Paton, J. C., Paton, A. W., Vermeulen, L., Medema, J. P., & BRINK, G. R. V. D. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.09.016 · Cited by 80
Melatonin improves insulin resistance and hepatic steatosis through attenuation of alpha‐2‐ HS ‐glycoprotein
Heo, J., Yoon, D. W., Yu, J. H., Kim, N. H., Yoo, H. J., Seo, J. A., Kim, S. G., Choi, K. M., Baik, S. H., Choi, D. S., et al. (2018) · Journal of Pineal Research · doi:10.1111/jpi.12493 · Cited by 80
Fibrillary Glomerulonephritis
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The unfolded protein response in retinal vascular diseases: Implications and therapeutic potential beyond protein folding
Zhang, S. X., Ma, J. H., Bhatta, M., Fliesler, S. J., & Wang, J. J. (2014) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2014.12.001 · Cited by 79
Hematopoietic stem cells preferentially traffic misfolded proteins to aggresomes and depend on aggrephagy to maintain protein homeostasis
Chua, B. A., Lennan, C., Sunshine, M. J., Dreifke, D., Chawla, A., Bennett, E. J., & Signer, R. A. J. (2023) · Cell stem cell · doi:10.1016/j.stem.2023.02.010 · Cited by 74
The PERK arm of the unfolded protein response regulates satellite cell-mediated skeletal muscle regeneration
Xiong, G., Hindi, S. M., Mann, A. K., Gallot, Y. S., Bohnert, K. R., Cavener, D. R., Whittemore, S. R., & Kumar, A. (2017) · eLife · doi:10.7554/elife.22871 · Cited by 74
Sensitization of ovarian cancer cells to cisplatin by gold nanoparticles
Xiong, X., Arvizo, R. R., Saha, S., Robertson, D. J., McMeekin, S., Bhattacharya, R., & Mukherjee, P. (2014) · Oncotarget · doi:10.18632/oncotarget.2203 · Cited by 73
New developments in the diagnosis of fibrillary glomerulonephritis
Nasr, S. H., & Fogo, A. B. (2019) · Kidney International · doi:10.1016/j.kint.2019.03.021 · Cited by 72
Early activation of inflammatory pathways in UBA1-mutated hematopoietic stem and progenitor cells in VEXAS
Wu, Z., Gao, S., Gao, Q., Patel, B. A., Groarke, E. M., Feng, X., Manley, A. L., Li, H., Cardona, D. O., Kajigaya, S., et al. (2023) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101160 · Cited by 75
ER-associated degradation preserves hematopoietic stem cell quiescence and self-renewal by restricting mTOR activity
Liu, L., Inoki, A., Fan, K., Mao, F., Shi, G., Jin, X., Zhao, M., Ney, G. M., Jones, M., Sun, S., et al. (2020) · Blood · doi:10.1182/blood.2020007975 · Cited by 62
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D’Aniello, C., Fico, A., Casalino, L., Guardiola, O., Napoli, G. D., Cermola, F., Cesare, D. D., Tatè, R., Cobellis, G., Patriarca, E. J., et al. (2015) · Cell Death and Differentiation · doi:10.1038/cdd.2015.24 · Cited by 64
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Chern, Y., & Tai, I. T. (2020) · Cancer Biology and Medicine · doi:10.20892/j.issn.2095-3941.2020.0005 · Cited by 67
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Li, J., Yang, S., Li, X., Liu, D., Wang, Z., Guo, J., Tan, N., Gao, Z., Zhao, X., Zhang, J., et al. (2016) · Bone · doi:10.1016/j.bone.2016.12.009 · Cited by 61
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Gallot, Y. S., & Bohnert, K. R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052567 · Cited by 61
Differential redox-regulation and mitochondrial dynamics in normal and leukemic hematopoietic stem cells: A potential window for leukemia therapy
Mattes, K., Vellenga, E., & Schepers, H. (2019) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2019.102814 · Cited by 62
Protein quality control through endoplasmic reticulum-associated degradation maintains haematopoietic stem cell identity and niche interactions
Xu, L., Liu, X., Peng, F., Zhang, W., Zheng, L., Ding, Y., Gu, T., Lv, K., Wang, J., Ortinau, L. C., et al. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-00581-x · Cited by 57
Canonical NF‐κB signaling in hepatocytes acts as a tumor‐suppressor in hepatitis B virus surface antigen‐driven hepatocellular carcinoma by controlling the unfolded protein response
Sunami, Y., Ringelhan, M., Kókai, E., Lu, M., O'Connor, T., Lorentzen, A., Weber, A., Rodewald, A., Müllhaupt, B., Terracciano, L., et al. (2016) · Hepatology · doi:10.1002/hep.28435 · Cited by 52
Low-intensity pulsed ultrasound upregulates osteogenesis under inflammatory conditions in periodontal ligament stem cells through unfolded protein response
Li, H., Deng, Y., Tan, M., Feng, G., Kuang, Y., Li, J., & Song, J. (2020) · Stem Cell Research & Therapy · doi:10.1186/s13287-020-01732-5 · Cited by 56
Understanding ER homeostasis and the UPR to enhance treatment efficacy of acute myeloid leukemia
Śniegocka, M., Liccardo, F., Fazi, F., & Masciarelli, S. (2022) · Drug Resistance Updates · doi:10.1016/j.drup.2022.100853 · Cited by 54
Misfolding, Aggregation, and Disordered Segments in c-Abl and p53 in Human Cancer
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A Drosophila Reporter for the Translational Activation of ATF4 Marks Stressed Cells during Development
Kang, K., Ryoo, H. D., Park, J., Yoon, J., & Kang, M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0126795 · Cited by 52
ER Stress and Unfolded Protein Response in Leukemia: Friend, Foe, or Both?
Féral, K., Jaud, M., Philippe, C., Bella, D. D., Pyronnet, S., Rouault‐Pierre, K., Mazzolini, L., & Touriol, C. (2021) · Biomolecules · doi:10.3390/biom11020199 · Cited by 62
INPP4B overexpression is associated with poor clinical outcome and therapy resistance in acute myeloid leukemia
Dzneladze, I., He, R., Woolley, J. F., Son, M. H., Sharobim, M., Greenberg, S. A., Gabra, M., Langlois, C., Rashid, A., Hakem, A., et al. (2015) · Leukemia · doi:10.1038/leu.2015.51 · Cited by 52

Authors: van Galen, P., Kreso, A., Mbong, N., Kent, D. G., Fitzmaurice, T., Chambers, J. E., Xie, S., Laurenti, E., Hermans, K., Eppert, K., Marciniak, S. J., Goodall, J. C., Green, A. R., Wouters, B. G., Wienholds, E., & Dick, J. E.
Affiliations: University Health Network (CA)
Wellcome/MRC Cambridge Stem Cell Institute (GB)
McGill University Health Centre (CA)
University of Cambridge (GB)
Corresponding author: Dick, John E.
ORCID: Kent, David G.
Chambers, Joseph E.
Xie, Stephanie
Laurenti, Elisa
Hermans, Karin
Eppert, Kolja
Marciniak, Stefan J.
Goodall, Jane C.
Green, Anthony R.
Wouters, Bradly G.
Dick, John E.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2014-04-28
Volume: 510
Issue: 7504
Pages: 268-272
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature13228
OpenAlex: W1999203943
Cited by: 363
References: 40
Citations by year: 2026: 11 · 2025: 31 · 2024: 23 · 2023: 28 · 2022: 27 · 2021: 24 · 2020: 51 · 2019: 34 · 2018: 32 · 2017: 33 · 2016: 22 · 2015: 34 · 2014: 12
FWCI: 23.87
Type: journal article
Language: en
Open access: green
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Apollo (University of Cambridge) (submittedVersion)
Apollo
Funders: Wellcome Trust (100140, 100140/Z/12/Z)
Cancer Research UK
Hospital for Sick Children
Versus Arthritis (19639)
Canadian Institutes of Health Research (201592)
Topics: Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
Keywords: hematopoietic stem cells, unfolded protein response, endoplasmic reticulum stress, PERK pathway, apoptosis, DNAJB9, stemness, leukemogenesis, HSC transplantation
MeSH terms: Animals, Hematopoietic Stem Cells, Humans, Male, Membrane Proteins, Tunicamycin, Signal Transduction, Eukaryotic Initiation Factor-2, Apoptosis, Protein Folding, Molecular Chaperones, eIF-2 Kinase, HSP40 Heat-Shock Proteins, Mice, Activating Transcription Factor 4, Transcription Factor CHOP, Protein Phosphatase 1, Unfolded Protein Response, Endoplasmic Reticulum Stress, Heterografts

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The unfolded protein response governs integrity of the haematopoietic stem-cell pool during stress

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