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Stem cell biology

DUSP16 is a regulator of human hematopoietic stem and progenitor cells and promotes their expansion ex vivo

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Fig. 1: DUSP16 overexpression enhanced ex vivo expansion of functional human CB HSC/HPC.
Fig. 2: HDACis upregulate DUSP16 expression through inhibition of HDAC1/HDAC3, and functionally mimic DUSP16 overexpression.

References

  1. Broxmeyer HE, Douglas GW, Hangoc G, Cooper S, Bard J, English D, et al. Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells. Proc Natl Acad Sci USA. 1989;86:3828–32.

    Article  CAS  Google Scholar 

  2. Gluckman E, Broxmeyer HE, Auerbach AD, Friedman HS, Douglas GW, Devergie A, et al. Hematopoietic reconstitution in a patient with Fanconi’s anemia by means of umbilical-cord blood from an HLA-identical sibling. N Engl J Med. 1989;321:1174–8.

    Article  CAS  Google Scholar 

  3. Ballen KK, Gluckman E, Broxmeyer HE. Umbilical cord blood transplantation: the first 25 years and beyond. Blood. 2013;122:491–8.

    Article  CAS  Google Scholar 

  4. Mayani H, Wagner JE, Broxmeyer HE. Cord blood research, banking, and transplantation: achievements, challenges, and perspectives. Bone Marrow Transplant. 2020;55:48–61.

    Article  Google Scholar 

  5. Huang X, Guo B, Capitano M, Broxmeyer HE. Past, present, and future efforts to enhance the efficacy of cord blood hematopoietic cell transplantation. F1000Res. 2019;8(F1000 Faculty Rev):1833.

    Article  Google Scholar 

  6. Guo B, Huang X, Lee MR, Lee SA, Broxmeyer HE. Antagonism of PPAR-gamma signaling expands human hematopoietic stem and progenitor cells by enhancing glycolysis. Nat Med. 2018;24:360–7.

    Article  CAS  Google Scholar 

  7. Rentas S, Holzapfel N, Belew MS, Pratt G, Voisin V, Wilhelm BT, et al. Musashi-2 attenuates AHR signalling to expand human haematopoietic stem cells. Nature. 2016;532:508–11.

    Article  Google Scholar 

  8. Baudet A, Karlsson C, Safaee Talkhoncheh M, Galeev R, Magnusson M, Larsson J. RNAi screen identifies MAPK14 as a druggable suppressor of human hematopoietic stem cell expansion. Blood. 2012;119:6255–8.

    Article  CAS  Google Scholar 

  9. Cellot S, Hope KJ, Chagraoui J, Sauvageau M, Deneault E, MacRae T, et al. RNAi screen identifies Jarid1b as a major regulator of mouse HSC activity. Blood. 2013;122:1545–55.

    Article  CAS  Google Scholar 

  10. Horlbeck MA, Gilbert LA, Villalta JE, Adamson B, Pak RA, Chen Y, et al. Compact and highly active next-generation libraries for CRISPR-mediated gene repression and activation. Elife. 2016;5:e19760.

    Article  Google Scholar 

  11. Liu X, Zhang CS, Lu C, Lin SC, Wu JW, Wang ZX. A conserved motif in JNK/p38-specific MAPK phosphatases as a determinant for JNK1 recognition and inactivation. Nat Commun. 2016;7:10879.

    Article  CAS  Google Scholar 

  12. Masuda K, Shima H, Watanabe M, Kikuchi K. MKP-7, a novel mitogen-activated protein kinase phosphatase, functions as a shuttle protein. J Biol Chem. 2001;276:39002–11.

    Article  CAS  Google Scholar 

  13. Chen Y, Yao C, Teng Y, Jiang R, Huang X, Liu S, et al. Phorbol ester induced ex vivo expansion of rigorously-defined phenotypic but not functional human cord blood hematopoietic stem cells: a cautionary tale demonstrating that phenotype does not always recapitulate stem cell function. Leukemia. 2019;33:2962–6.

    Article  Google Scholar 

  14. Minucci S, Pelicci PG. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer. 2006;6:38–51.

    Article  CAS  Google Scholar 

  15. Musikacharoen T, Yoshikai Y, Matsuguchi T. Histone acetylation and activation of cAMP-response element-binding protein regulate transcriptional activation of MKP-M in lipopolysaccharide-stimulated macrophages. J Biol Chem. 2003;278:9167–75.

    Article  CAS  Google Scholar 

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Acknowledgements

These studies were supported by US Public Health Service grants R35 HL139599, R01 DK109188, and U54 DK106846 from the National Institute of Health to HEB. The in vivo Therapeutics Core and the Flow Cytometry Facility of the Indiana University School of Medicine, funded in part by U54 DK106846, for assistance.

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XW and HEB conceived the project and designed the experiments. XW performed the experiments and analyzed the data. XW and HEB wrote and edited the paper.

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Correspondence to Hal E. Broxmeyer.

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Wang, X., Broxmeyer, H.E. DUSP16 is a regulator of human hematopoietic stem and progenitor cells and promotes their expansion ex vivo. Leukemia 35, 1516–1520 (2021). https://doi.org/10.1038/s41375-020-01064-6

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