Hypersensitivity Response Has Negligible Impact on Hematopoietic Stem Cells

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2021 Jul 23

PMID 34297939

Citations 1

Authors

Nir Bujanover

Roshina Thapa

Oron Goldstein

Leonid Olender

Omri Sharabi

Michael D Milsom

Roi Gazit

Affiliations

Soon will be listed here.

Abstract

Immune cells are generated from hematopoietic stem cells (HSCs) in the bone marrow (BM). Immune stimulation can rapidly activate HSCs out of their quiescent state to accelerate the generation of immune cells. HSCs' activation follows various viral or bacterial stimuli, and we sought to investigate the hypersensitivity immune response. Surprisingly, the Ova-induced hypersensitivity peritonitis model finds no significant changes in BM HSCs. HSC markers cKIT, SCA1, CD48, CD150, and the Fgd5-mCherry reporter showed no significant difference from control. Functionally, hypersensitivity did not alter HSCs' potency, as assayed by transplantation. We further characterized the possible impact of hypersensitivity using RNA-sequencing of HSCs, finding minor changes at the transcriptome level. Moreover, hypersensitivity induced no significant change in the proliferative state of HSCs. Therefore, this study suggests that, in contrast to other immune stimuli, hypersensitivity has no impact on HSCs.

Citing Articles

Rapid activation of hematopoietic stem cells.

Thapa R, Elfassy E, Olender L, Sharabi O, Gazit R Stem Cell Res Ther. 2023; 14(1):152.

PMID: 37280691 PMC: 10245525. DOI: 10.1186/s13287-023-03377-6.

References

Flach J, Bakker S, Mohrin M, Conroy P, Pietras E, Reynaud D . Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells. Nature. 2014; 512(7513):198-202. PMC: 4456040. DOI: 10.1038/nature13619. View

Zhang C, Yi W, Li F, Du X, Wang H, Wu P . Eosinophil-derived CCL-6 impairs hematopoietic stem cell homeostasis. Cell Res. 2018; 28(3):323-335. PMC: 5835778. DOI: 10.1038/cr.2018.2. View

Sato T, Onai N, Yoshihara H, Arai F, Suda T, Ohteki T . Interferon regulatory factor-2 protects quiescent hematopoietic stem cells from type I interferon-dependent exhaustion. Nat Med. 2009; 15(6):696-700. DOI: 10.1038/nm.1973. View

Kiel M, Yilmaz O, Iwashita T, Yilmaz O, Terhorst C, Morrison S . SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell. 2005; 121(7):1109-21. DOI: 10.1016/j.cell.2005.05.026. View

Golan K, Kumari A, Kollet O, Khatib-Massalha E, Subramaniam M, Ferreira Z . Daily Onset of Light and Darkness Differentially Controls Hematopoietic Stem Cell Differentiation and Maintenance. Cell Stem Cell. 2018; 23(4):572-585.e7. DOI: 10.1016/j.stem.2018.08.002. View

Pang W, Schrier S, Weissman I . Age-associated changes in human hematopoietic stem cells. Semin Hematol. 2017; 54(1):39-42. DOI: 10.1053/j.seminhematol.2016.10.004. View

Christensen J, Weissman I . Flk-2 is a marker in hematopoietic stem cell differentiation: a simple method to isolate long-term stem cells. Proc Natl Acad Sci U S A. 2001; 98(25):14541-6. PMC: 64718. DOI: 10.1073/pnas.261562798. View

Chambers S, Shaw C, Gatza C, Fisk C, Donehower L, Goodell M . Aging hematopoietic stem cells decline in function and exhibit epigenetic dysregulation. PLoS Biol. 2007; 5(8):e201. PMC: 1925137. DOI: 10.1371/journal.pbio.0050201. View

Walter D, Lier A, Geiselhart A, Thalheimer F, Huntscha S, Sobotta M . Exit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells. Nature. 2015; 520(7548):549-52. DOI: 10.1038/nature14131. View

10.

Leduc D, Vargaftig B, Pretolani M . Characterization and pharmacological modulation of antigen-induced peritonitis in actively sensitized mice. Br J Pharmacol. 1993; 110(2):917-24. PMC: 2175902. DOI: 10.1111/j.1476-5381.1993.tb13900.x. View

11.

Spangrude G, Heimfeld S, Weissman I . Purification and characterization of mouse hematopoietic stem cells. Science. 1988; 241(4861):58-62. DOI: 10.1126/science.2898810. View

12.

Haas S, Hansson J, Klimmeck D, Loeffler D, Velten L, Uckelmann H . Inflammation-Induced Emergency Megakaryopoiesis Driven by Hematopoietic Stem Cell-like Megakaryocyte Progenitors. Cell Stem Cell. 2015; 17(4):422-34. DOI: 10.1016/j.stem.2015.07.007. View

13.

Bradfute S, Graubert T, Goodell M . Roles of Sca-1 in hematopoietic stem/progenitor cell function. Exp Hematol. 2005; 33(7):836-43. DOI: 10.1016/j.exphem.2005.04.001. View

14.

Pronk C, Veiby O, Bryder D, Jacobsen S . Tumor necrosis factor restricts hematopoietic stem cell activity in mice: involvement of two distinct receptors. J Exp Med. 2011; 208(8):1563-70. PMC: 3149225. DOI: 10.1084/jem.20110752. View

15.

De Luca K, Frances-Duvert V, Asensio M, Ihsani R, Debien E, Taillardet M . The TLR1/2 agonist PAM(3)CSK(4) instructs commitment of human hematopoietic stem cells to a myeloid cell fate. Leukemia. 2009; 23(11):2063-74. DOI: 10.1038/leu.2009.155. View

16.

Allakhverdi Z, Comeau M, Smith D, Toy D, Endam L, Desrosiers M . CD34+ hemopoietic progenitor cells are potent effectors of allergic inflammation. J Allergy Clin Immunol. 2008; 123(2):472-8. DOI: 10.1016/j.jaci.2008.10.022. View

17.

Essers M, Offner S, Blanco-Bose W, Waibler Z, Kalinke U, Duchosal M . IFNalpha activates dormant haematopoietic stem cells in vivo. Nature. 2009; 458(7240):904-8. DOI: 10.1038/nature07815. View

18.

Hernandez G, Mills T, Rabe J, Chavez J, Kuldanek S, Kirkpatrick G . Pro-inflammatory cytokine blockade attenuates myeloid expansion in a murine model of rheumatoid arthritis. Haematologica. 2019; 105(3):585-597. PMC: 7049366. DOI: 10.3324/haematol.2018.197210. View

19.

Matatall K, Jeong M, Chen S, Sun D, Chen F, Mo Q . Chronic Infection Depletes Hematopoietic Stem Cells through Stress-Induced Terminal Differentiation. Cell Rep. 2016; 17(10):2584-2595. PMC: 5161248. DOI: 10.1016/j.celrep.2016.11.031. View

20.

Kim I, He S, Yilmaz O, Kiel M, Morrison S . Enhanced purification of fetal liver hematopoietic stem cells using SLAM family receptors. Blood. 2006; 108(2):737-44. PMC: 1895480. DOI: 10.1182/blood-2005-10-4135. View