Re-entry into quiescence protects hematopoietic stem cells from the killing effect of chronic exposure to type I interferons
Open accessAbstract
Type I interferons (IFN-1s) are antiviral cytokines that suppress blood production while paradoxically inducing hematopoietic stem cell (HSC) proliferation. Here, we clarify the relationship between the proliferative and suppressive effects of IFN-1s on HSC function during acute and chronic IFN-1 exposure. We show that IFN-1–driven HSC proliferation is a transient event resulting from a brief relaxation of quiescence-enforcing mechanisms in response to acute IFN-1 exposure, which occurs exclusively in vivo. We find that this proliferative burst fails to exhaust the HSC pool, which rapidly returns to quiescence in response to chronic IFN-1 exposure. Moreover, we demonstrate that IFN-1–exposed HSCs with reestablished quiescence are largely protected from the killing effects of IFNs unless forced back into the cell cycle due to culture, transplantation, or myeloablative treatment, at which point they activate a p53-dependent proapoptotic gene program. Collectively, our results demonstrate that quiescence acts as a safeguard mechanism to ensure survival of the HSC pool during chronic IFN-1 exposure. We show that IFN-1s can poise HSCs for apoptosis but induce direct cell killing only upon active proliferation, thereby establishing a mechanism for the suppressive effects of IFN-1s on HSC function.
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Chronic pro-inflammatory signaling due to chronic infections or repetitive sterile inflammation is detrimental to HSPC self-renewal, promoting loss of quiescence and differentiation.
“Chronic pro-inflammatory signaling due to chronic infections or repetitive sterile inflammation, however, has been shown to be detrimental to HSPC self-renewal, promoting loss of quiescence and differentiation [61–65].”
From Clonal hematopoiesis and inflammation – the perpetual cycle (2023) · cites this paper as [64]
The Results section ('Reacquisition of quiescence in IFN-exposed HSCs fails to restore HSC function'; page unavailable) reports impaired HSC function after chronic type I interferon exposure. But the Discussion says HSCs re-enter quiescence and mostly remain dormant during chronic exposure, contrary to the claimed ongoing loss of quiescence. The cited passages do not show that the impairment is driven by differentiation, or establish the same mechanism for chronic infections and repetitive sterile inflammation. (LLM, conf=0.88)
Experimental — accuracy not yet measuredp53 has diverse functions in hematopoietic stem cell responses to inflammation, which can be broadly classified as survival, apoptosis, and cell-cycle depending on the context.
“p53 has diverse functions in HSC responses to inflammation (28), which can be broadly classified as survival, apoptosis, and cell-cycle depending on the context.”
From <i>Txnip</i> Enhances Fitness of <i>Dnmt3a</i> -Mutant Hematopoietic Stem Cells via <i>p21</i> (2022) · cites this paper as [28]
The Results section (“Function of p53 in IFN-1–exposed HSCs”; page unavailable) shows that p53 promotes an apoptotic response to IFN-α and notes its established role in HSC quiescence. But the same experiments found that loss of p53 did not significantly change IFN-1–induced proliferation or return to quiescence. The paper attributes survival during chronic exposure to re-entry into quiescence, not specifically to a survival function of p53, so it does not establish all the functions implied by the claim. (LLM, conf=0.85)
Experimental — accuracy not yet measuredOther mechanism(s) may enforce HSC quiescence under chronic IFN stimulation, such as activation of p53 and/or the mRNA translation-blocking activity of several IFN-stimulated genes.
“suggesting that other mechanism(s) may enforce HSC quiescence under chronic IFN stimulation, such as activation of p53 and/or the mRNA translation-blocking activity of several IFN-stimulated genes (Li et al., 2015; Pietras et al., 2014).”
From PU.1 enforces quiescence and limits hematopoietic stem cell expansion during inflammatory stress (2021) · cites this paper as Pietras et al., 2014
The Results and Discussion (page numbers unavailable) report that multiple quiescence-enforcing mechanisms are reactivated during chronic type I IFN exposure, including recovery of p53 gene expression. They do not establish p53 activation as the mechanism: HSCs lacking p53 returned to quiescence without significant delay. The passages do not support the proposed mRNA translation-blocking activity of IFN-stimulated genes. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIsolated effects of individual inflammatory cytokines, including type 1 interferons (IFNa/b), type 2 IFN (IFNg), TNFa, and IL-1, have been well-documented in mouse hematopoietic development.
“The isolated effects of individual inflammatory cytokines, including type 1 interferons (IFNa/b) 1-3 , type 2 IFN (IFNg) 4-6 , TNFa 7,8 , and IL-1 9-11 , have been well-documented in mouse hematopoietic development.”
From Type 1 interferon perturbates clonal competition by reshaping human blood development (2026) · cites this paper as [10]
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Wilson, A., Laurenti, E., Oser, G., van der Wath, R. C., Blanco-Bose, W., Jaworski, M., Offner, S., Dunant, C. F., Eshkind, L., Bockamp, E., et al. (2008) · Cell · doi:10.1016/j.cell.2008.10.048 · Cited by 1,908 · see citing works
FOXO3A directs a protective autophagy program in haematopoietic stem cells
Warr, M. R., Binnewies, M., Flach, J., Reynaud, D., Garg, T., Malhotra, R., Debnath, J., & Passegué, E. (2013) · Nature · doi:10.1038/nature11895 · Cited by 625 · see citing works
Self-citationYamazaki, S., Iwama, A., Takayanagi, S., Morita, Y., Eto, K., Ema, H., & Nakauchi, H. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601236 · Cited by 270 · see citing works
Flagged first, then by citations
Research works printed but not linked: 40
- Bakker S.T. Passegué E. 2013 Resilient and resourceful: genome maintenance strategies in hematopoietic stem cells. Exp. Hematol. 41: 915– 923 (Epub ahead of print) 10.1016/j.exphem.2013.09.007 24067363 PMC3833969 · DOI
- Baldridge M.T. King K.Y. Boles N.C. Weksberg D.C. Goodell M.A. 2010 Quiescent haematopoietic stem cells are activated by IFN-gamma in response to chronic infection. Nature. 465: 793– 797 10.1038/nature09135 20535209 PMC2935898 · DOI · Paper page
- Brenet F. Kermani P. Spektor R. Rafii S. Scandura J.M. 2013 TGFβ restores hematopoietic homeostasis after myelosuppressive chemotherapy. J. Exp. Med. 210: 623– 639 10.1084/jem.20121610 23440043 PMC3600905 · DOI
- Castrillon D.H. Miao L. Kollipara R. Horner J.W. DePinho R.A. 2003 Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a. Science. 301: 215– 218 10.1126/science.1086336 12855809 · DOI
- Chen C. Liu Y. Liu Y. Zheng P. 2009 mTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells. Sci. Signal. 2: ra75 19934433 PMC4020596
- Davis L.S. Hutcheson J. Mohan C. 2011 The role of cytokines in the pathogenesis and treatment of systemic lupus erythematosus. J. Interferon Cytokine Res. 31: 781– 789 10.1089/jir.2011.0047 21787222 PMC3189549 · DOI
- de Bruin A.M. Demirel O. Hooibrink B. Brandts C.H. Nolte M.A. 2013 Interferon-γ impairs proliferation of hematopoietic stem cells in mice. Blood. 121: 3578– 3585 10.1182/blood-2012-05-432906 23487025 · DOI
- Donehower L.A. Harvey M. Slagle B.L. McArthur M.J. Montgomery C.A. Jr Butel J.S. Bradley A. 1992 Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature. 356: 215– 221 10.1038/356215a0 1552940 · DOI · Paper page
- Dumont F.J. Coker L.Z. 1986 Interferon-α/β enhances the expression of Ly-6 antigens on T cells in vivo and in vitro. Eur. J. Immunol. 16: 735– 740 10.1002/eji.1830160704 3487457 · DOI
- Essers M.A. Offner S. Blanco-Bose W.E. Waibler Z. Kalinke U. Duchosal M.A. Trumpp A. 2009 IFNalpha activates dormant haematopoietic stem cells in vivo. Nature. 458: 904– 908 10.1038/nature07815 19212321 · DOI · Paper page
- Feng C.G. Weksberg D.C. Taylor G.A. Sher A. Goodell M.A. 2008 The p47 GTPase Lrg-47 (Irgm1) links host defense and hematopoietic stem cell proliferation. Cell Stem Cell. 2: 83– 89 10.1016/j.stem.2007.10.007 18371424 PMC2278017 · DOI
- Frelin C. Herrington R. Janmohamed S. Barbara M. Tran G. Paige C.J. Benveniste P. Zuñiga-Pflücker J.C. Souabni A. Busslinger M. Iscove N.N. 2013 GATA-3 regulates the self-renewal of long-term hematopoietic stem cells. Nat. Immunol. 14: 1037– 1044 10.1038/ni.2692 23974957 PMC4972578 · DOI
- Goff D.J. Recart A.C. Sadarangani A. Chun H.J. Barrett C.L. Krajewska M. Leu H. Low-Marchelli J. Ma W. Shih A.Y. 2013 A Pan-BCL2 inhibitor renders bone-marrow-resident human leukemia stem cells sensitive to tyrosine kinase inhibition. Cell Stem Cell. 12: 316– 328 10.1016/j.stem.2012.12.011 23333150 PMC3968867 · DOI
- Gokce M. Bilginer Y. Besbas N. Ozaltin F. Cetin M. Gumruk F. Ozen S. 2012 Hematological features of pediatric systemic lupus erythematosus: suggesting management strategies in children. Lupus. 21: 878– 884 10.1177/0961203312443721 22495873 · DOI
- Hartner J.C. Walkley C.R. Lu J. Orkin S.H. 2009 ADAR1 is essential for the maintenance of hematopoiesis and suppression of interferon signaling. Nat. Immunol. 10: 109– 115 10.1038/ni.1680 19060901 PMC2701568 · DOI
- Ioannou S. Hatzis G. Vlahadami I. Voulgarelis M. 2010 Aplastic anemia associated with interferon alpha 2a in a patient with chronic hepatitis C virus infection: a case report. J. Med. Case Reports. 4: 268 10.1186/1752-1947-4-268 PMC2925355 20704699 · DOI
- Kiladjian J.J. Mesa R.A. Hoffman R. 2011 The renaissance of interferon therapy for the treatment of myeloid malignancies. Blood. 117: 4706– 4715 10.1182/blood-2010-08-258772 21389325 · DOI
- King K.Y. Baldridge M.T. Weksberg D.C. Chambers S.M. Lukov G.L. Wu S. Boles N.C. Jung S.Y. Qin J. Liu D. 2011 Irgm1 protects hematopoietic stem cells by negative regulation of IFN signaling. Blood. 118: 1525– 1533 10.1182/blood-2011-01-328682 21633090 PMC3156044 · DOI
- Kunisaki Y. Bruns I. Scheiermann C. Ahmed J. Pinho S. Zhang D. Mizoguchi T. Wei Q. Lucas D. Ito K. 2013 Arteriolar niches maintain haematopoietic stem cell quiescence. Nature. 502: 637– 643 10.1038/nature12612 24107994 PMC3821873 · DOI
- Lin K.K. Rossi L. Boles N.C. Hall B.E. George T.C. Goodell M.A. 2011 CD81 is essential for the re-entry of hematopoietic stem cells to quiescence following stress-induced proliferation via deactivation of the Akt pathway. PLoS Biol. 9: e1001148 10.1371/journal.pbio.1001148 21931533 PMC3172193 · DOI
- Mohrin M. Bourke E. Alexander D. Warr M.R. Barry-Holson K. Le Beau M.M. Morrison C.G. Passegué E. 2010 Hematopoietic stem cell quiescence promotes error-prone DNA repair and mutagenesis. Cell Stem Cell. 7: 174– 185 10.1016/j.stem.2010.06.014 20619762 PMC2924905 · DOI · Paper page
- Mullally A. Bruedigam C. Poveromo L. Heidel F.H. Purdon A. Vu T. Austin R. Heckl D. Breyfogle L.J. Kuhn C.P. 2013 Depletion of Jak2V617F myeloproliferative neoplasm-propagating stem cells by interferon-α in a murine model of polycythemia vera. Blood. 121: 3692– 3702 10.1182/blood-2012-05-432989 23487027 PMC3643767 · DOI
- Müller U. Steinhoff U. Reis L.F. Hemmi S. Pavlovic J. Zinkernagel R.M. Aguet M. 1994 Functional role of type I and type II interferons in antiviral defense. Science. 264: 1918– 1921 10.1126/science.8009221 8009221 · DOI
- Ooi A.G. Karsunky H. Majeti R. Butz S. Vestweber D. Ishida T. Quertermous T. Weissman I.L. Forsberg E.C. 2009 The adhesion molecule esam1 is a novel hematopoietic stem cell marker. Stem Cells. 27: 653– 661 19074415 PMC4186794
- Opferman J.T. Iwasaki H. Ong C.C. Suh H. Mizuno S. Akashi K. Korsmeyer S.J. 2005 Obligate role of anti-apoptotic MCL-1 in the survival of hematopoietic stem cells. Science. 307: 1101– 1104 10.1126/science.1106114 15718471 · DOI
- Orford K.W. Scadden D.T. 2008 Deconstructing stem cell self-renewal: genetic insights into cell-cycle regulation. Nat. Rev. Genet. 9: 115– 128 10.1038/nrg2269 18202695 · DOI · Paper page
- Passegué E. Ernst P. 2009 IFN-alpha wakes up sleeping hematopoietic stem cells. Nat. Med. 15: 612– 613 10.1038/nm0609-612 19498372 PMC2892628 · DOI
- Pietras E.M. Warr M.R. Passegué E. 2011 Cell cycle regulation in hematopoietic stem cells. J. Cell Biol. 195: 709– 720 10.1083/jcb.201102131 22123859 PMC3257565 · DOI · Paper page
- Platanias L.C. 2005 Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat. Rev. Immunol. 5: 375– 386 10.1038/nri1604 15864272 · DOI
- Santaguida M. Schepers K. King B. Sabnis A.J. Forsberg E.C. Attema J.L. Braun B.S. Passegué E. 2009 JunB protects against myeloid malignancies by limiting hematopoietic stem cell proliferation and differentiation without affecting self-renewal. Cancer Cell. 15: 341– 352 10.1016/j.ccr.2009.02.016 19345332 PMC2669108 · DOI
- Sato T. Onai N. Yoshihara H. Arai F. Suda T. Ohteki T. 2009 Interferon regulatory factor-2 protects quiescent hematopoietic stem cells from type I interferon-dependent exhaustion. Nat. Med. 15: 696– 700 10.1038/nm.1973 19483695 · DOI
- Szodoray P. Varoczy L. Papp G. Barath S. Nakken B. Szegedi G. Zeher M. 2012 Immunological reconstitution after autologous stem cell transplantation in patients with refractory systemic autoimmune diseases. Scand. J. Rheumatol. 41: 110– 115 10.3109/03009742.2011.606788 21936606 · DOI
- Takaoka A. Hayakawa S. Yanai H. Stoiber D. Negishi H. Kikuchi H. Sasaki S. Imai K. Shibue T. Honda K. Taniguchi T. 2003 Integration of interferon-αβ signalling to p53 resonses in tumour suppression and antiviral defence. Nature. 424: 517– 523 12872134
- Talpaz M. Kantarjian H. Kurzrock R. Trujillo J.M. Gutterman J.U. 1991 Interferon-alpha produces sustained cytogenetic responses in chronic myelogenous leukemia. Philadelphia chromosome-positive patients. Ann. Intern. Med. 114: 532– 538 10.7326/0003-4819-114-7-532 2001086 · DOI
- Tamura T. Yanai H. Savitsky D. Taniguchi T. 2008 The IRF family transcription factors in immunity and oncogenesis. Annu. Rev. Immunol. 26: 535– 584 10.1146/annurev.immunol.26.021607.090400 18303999 · DOI · Paper page
- Tyndall A. 2011 Successes and failures of stem cell transplantation in autoimmune diseases. Hematology (Am Soc Hematol Educ Program). 2011: 280– 284 10.1182/asheducation-2011.1.280 22160046 · DOI
- Verma A. Deb D.K. Sassano A. Uddin S. Varga J. Wickrema A. Platanias L.C. 2002 Activation of the p38 mitogen-activated protein kinase mediates the suppressive effects of type I interferons and transforming growth factor-β on normal hematopoiesis. J. Biol. Chem. 277: 7726– 7735 10.1074/jbc.M106640200 11773065 · DOI
- Yamazaki S. Iwama A. Takayanagi S. Eto K. Ema H. Nakauchi H. 2009 TGF-beta as a candidate bone marrow niche signal to induce hematopoietic stem cell hibernation. Blood. 113: 1250– 1256 18945958
- Zhao X. Ren G. Liang L. Ai P. Zheng B. Tischfield J. Shi Y. Shao C. 2009 Brief Report-IFNgamma Induces Expansion of Lin-Sca-1+C-Kit+ Cells. Stem Cells. 28: 122– 126 19890981
- Zhou L. Opalinska J. Verma A. 2007 p38 MAP kinase regulates stem cell apoptosis in human hematopoietic failure. Cell Cycle. 6: 534– 537 10.4161/cc.6.5.3921 17351344 · DOI
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- Authors
- Pietras, E. M., Lakshminarasimhan, R., Techner, J.-M., Fong, S., Flach, J., Binnewies, M., & Passegué, E.
- Affiliations
- University of California, San Francisco (US)
- The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Department of Medicine, Division of Hematology/Oncology, University of California San Francisco, San Francisco, California 94143
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2014-02-03
- Volume
- 211
- Issue
- 2
- Pages
- 245-262
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC3920566
- OpenAlex
- W2169841221
- Cited by
- 323
- References
- 3
- Citations by year
- 2026: 19 · 2025: 29 · 2024: 33 · 2023: 33 · 2022: 30 · 2021: 35 · 2020: 31 · 2019: 22 · 2018: 20 · 2017: 18 · 2016: 24 · 2015: 23 · 2014: 6
- FWCI
- 16.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL111266, R01HL092471, F32HL106989)
- National Cancer Institute (T32CA108462)
- National Institute of Allergy and Infectious Diseases (T32AI007334)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
- Keywords
- hematopoietic stem cells, type I interferon, stem cell quiescence, HSC proliferation, p53-dependent apoptosis
- MeSH terms
- Animals, Bone Marrow, Cell Survival, Female, Hematopoiesis, Hematopoietic Stem Cells, Interferon Type I, Male, Mice, Inbred C57BL, Signal Transduction, Tumor Suppressor Protein p53, Resting Phase, Cell Cycle, Apoptosis, Mice, Knockout, Mice, Congenic, Cell Proliferation, Mice, Cell Cycle Checkpoints
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