SIRT1 is dispensable for maturation of hematopoietic stem cell in the bone marrow niche

Park,Su Min; Kim,Jayoung; Hong,Chae Mi; Shin,Dong Hoon; Kim,Jee Yeon; Park,Do Youn; Sohn,Dong Hyun; Kim,Yun Hak; Kwon,Sang‑Mo; Kim,Jae Ho; Bae,Sun Sik; Kim,Koanhoi; Kim,Chi Dae; Kang,Chi‑Dug; Lee,Dongjun

doi:10.3892/etm.2019.7813

SIRT1 is dispensable for maturation of hematopoietic stem cell in the bone marrow niche

Authors:
- Su Min Park
- Jayoung Kim
- Chae Mi Hong
- Dong Hoon Shin
- Jee Yeon Kim
- Do Youn Park
- Dong Hyun Sohn
- Yun Hak Kim
- Sang‑Mo Kwon
- Jae Ho Kim
- Sun Sik Bae
- Koanhoi Kim
- Chi Dae Kim
- Chi‑Dug Kang
- Dongjun Lee
View Affiliations

Affiliations: Department of Convergence Medical Science, Pusan National University School of Medicine, Yangsan, Gyeongsangnam‑do 50612, Republic of Korea, Department of Pathology, Pusan National University School of Medicine, Yangsan, Gyeongsangnam‑do 50612, Republic of Korea, Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, Gyeongsangnam‑do 50612, Republic of Korea, Department of Anatomy and Biomedical Informatics, Biomedical Research Institute, Pusan National University School of Medicine, Yangsan, Gyeongsangnam‑do 50612, Republic of Korea, Department of Physiology, Pusan National University School of Medicine, Yangsan, Gyeongsangnam‑do 50612, Republic of Korea, Department of Pharmacology, Pusan National University School of Medicine, Yangsan, Gyeongsangnam‑do 50612, Republic of Korea
Published online on: July 25, 2019 https://doi.org/10.3892/etm.2019.7813
Pages: 2341-2345

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Sirtuin 1 (SIRT1) is a histone deacetylase implicated in stem cell homeostasis. Conditional Sirt1 deletion in the hematopoietic stem and progenitor system promotes hematopoietic stem and progenitor cell (HSPC) expansion under stress conditions. In addition, SIRT1 activators modulate the capacity and HSPC numbers in the bone marrow (BM). To investigate the role of SIRT1 in the BM niche, a conditional Sirt1 deletion in the BM niche was generated in a mouse model for the present study. Multicolor flow cytometric analyses were performed to determine HSC cell populations. Using 5‑fluorouracil‑induced proliferative stress, a survival curve was produced. In the present study, Sirt1 deletion in the BM niche demonstrated that the production of mature blood cells, lineage distribution within hematopoietic organs and frequencies of HSPC populations were comparable to those of controls. Additionally, Sirt1 deletion in the BM niche did not perturb HSC maturation under stress induced by transplantation. Therefore, these observations suggest that SIRT1 serves a dispensable role in HSC maturation in the BM niche.

View Figures

View References

1	Schofield R: The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells. 4:7–25. 1978.PubMed/NCBI
2	Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, Knight MC, Martin RP, Schipani E, Divieti P, Bringhurst FR, et al: Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 425:841–846. 2003. View Article : Google Scholar : PubMed/NCBI
3	Li L and Xie T: Stem cell niche: Structure and function. Annu Rev Cell Dev Biol. 21:605–631. 2005. View Article : Google Scholar : PubMed/NCBI
4	Trumpp A, Essers M and Wilson A: Awakening dormant haematopoietic stem cells. Nat Rev Immunol. 10:201–209. 2010. View Article : Google Scholar : PubMed/NCBI
5	Thomas ED: Bone marrow transplantation from the personal viewpoint. Int J Hematol. 81:89–93. 2005. View Article : Google Scholar : PubMed/NCBI
6	Lavu S, Boss O, Elliott PJ and Lambert PD: Sirtuins-novel therapeutic targets to treat age-associated diseases. Nat Rev Drug Discov. 7:841–853. 2008. View Article : Google Scholar : PubMed/NCBI
7	Park SY, Lee SW, Kim HY, Lee SY, Lee WS, Hong KW and Kim CD: SIRT1 inhibits differentiation of monocytes to macrophages: Amelioration of synovial inflammation in rheumatoid arthritis. J Mol Med (Berl). 94:921–931. 2016. View Article : Google Scholar : PubMed/NCBI
8	Park SY, Lee SW, Lee SY, Hong KW, Bae SS, Kim K and Kim CD: SIRT1/adenosine monophosphate-activated protein kinase α signaling enhances macrophage polarization to an anti-inflammatory phenotype in rheumatoid arthritis. Front Immunol. 8:11352017. View Article : Google Scholar : PubMed/NCBI
9	Han MK, Song EK, Guo Y, Ou X, Mantel C and Broxmeyer HE: SIRT1 regulates apoptosis and nanog expression in mouse embryonic stem cells by controlling p53 subcellular localization. Cell Stem Cell. 2:241–251. 2008. View Article : Google Scholar : PubMed/NCBI
10	Oberdoerffer P, Michan S, McVay M, Mostoslavsky R, Vann J, Park SK, Hartlerode A, Stegmuller J, Hafner A, Loerch P, et al: SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging. Cell. 135:907–918. 2008. View Article : Google Scholar : PubMed/NCBI
11	Wang RH, Sengupta K, Li C, Kim HS, Cao L, Xiao C, Kim S, Xu X, Zheng Y, Chilton B, et al: Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice. Cancer Cell. 14:312–323. 2008. View Article : Google Scholar : PubMed/NCBI
12	Ou X, Chae HD, Wang RH, Shelley WC, Cooper S, Taylor T, Kim YJ, Deng CX, Yoder MC and Broxmeyer HE: SIRT1 deficiency compromises mouse embryonic stem cell hematopoietic differentiation, and embryonic and adult hematopoiesis in the mouse. Blood. 117:440–450. 2011. View Article : Google Scholar : PubMed/NCBI
13	Singh SK, Williams CA, Klarmann K, Burkett SS, Keller JR and Oberdoerffer P: Sirt1 ablation promotes stress-induced loss of epigenetic and genomic hematopoietic stem and progenitor cell maintenance. J Exp Med. 210:987–1001. 2013. View Article : Google Scholar : PubMed/NCBI
14	Rimmele P, Bigarella CL, Liang R, Izac B, Dieguez-Gonzalez R, Barbet G, Donovan M, Brugnara C, Blander JM, Sinclair DA and Ghaffari S: Aging-like phenotype and defective lineage specification in SIRT1-deleted hematopoietic stem and progenitor cells. Stem Cell Reports. 3:44–59. 2014. View Article : Google Scholar : PubMed/NCBI
15	Leko V, Varnum-Finney B, Li H, Gu Y, Flowers D, Nourigat C, Bernstein ID and Bedalov A: SIRT1 is dispensable for function of hematopoietic stem cells in adult mice. Blood. 119:1856–1860. 2012. View Article : Google Scholar : PubMed/NCBI
16	Rimmele P, Lofek-Czubek S and Ghaffari S: Resveratrol increases the bone marrow hematopoietic stem and progenitor cell capacity. Am J Hematol. 89:E235–E238. 2014. View Article : Google Scholar : PubMed/NCBI
17	Zhang QS, Deater M, Schubert K, Marquez-Loza L, Pelz C, Sinclair DA and Grompe M: The Sirt1 activator SRT3025 expands hematopoietic stem and progenitor cells and improves hematopoiesis in fanconi anemia mice. Stem Cell Res. 15:130–140. 2015. View Article : Google Scholar : PubMed/NCBI
18	Zhang M, Xuan S, Bouxsein ML, von Stechow D, Akeno N, Faugere MC, Malluche H, Zhao G, Rosen CJ, Efstratiadis A and Clemens TL: Osteoblast-specific knockout of the insulin-like growth factor (IGF) receptor gene reveals an essential role of IGF signaling in bone matrix mineralization. J Biol Chem. 277:44005–44012. 2002. View Article : Google Scholar : PubMed/NCBI
19	Li H, Rajendran GK, Liu N, Ware C, Rubin BP and Gu Y: SirT1 modulates the estrogen-insulin-like growth factor-1 signaling for postnatal development of mammary gland in mice. Breast Cancer Res. 9:R12007. View Article : Google Scholar : PubMed/NCBI
20	Lee DH, Kim TS, Lee D and Lim DS: Mammalian sterile 20 kinase 1 and 2 are important regulators of hematopoietic stem cells in stress condition. Sci Rep. 8:9422018. View Article : Google Scholar : PubMed/NCBI
21	Deveza L, Ortinau L, Lei K and Park D: Comparative analysis of gene expression identifies distinct molecular signatures of bone marrow- and periosteal-skeletal stem/progenitor cells. PLoS One. 13:e01909092018. View Article : Google Scholar : PubMed/NCBI
22	Goncalves KA, Silberstein L, Li S, Severe N, Hu MG, Yang H, Scadden DT and Hu GF: Angiogenin promotes hematopoietic regeneration by dichotomously regulating quiescence of stem and progenitor cells. Cell. 166:894–906. 2016. View Article : Google Scholar : PubMed/NCBI
23	Thrall KD, Mahendra S, Jackson MK, Jackson W 3rd, Farese AM and MacVittie TJ: A comparative dose-response relationship between sexes for mortality and morbidity of radiation-induced lung injury in the rhesus macaque. Health Phys. 116:354–365. 2019. View Article : Google Scholar : PubMed/NCBI
24	Edin NF, Altaner C, Altanerova V, Ebbesen P and Pettersen EO: Low-dose-rate irradiation for 1 hour induces protection against lethal radiation doses but does not affect life span of DBA/2 mice. Dose Response. 14:15593258166739012016. View Article : Google Scholar : PubMed/NCBI
25	Wu J, Bao J, Kim M, Yuan S, Tang C, Zheng H, Mastick GS, Xu C and Yan W: Two miRNA clusters, miR-34b/c and miR-449, are essential for normal brain development, motile ciliogenesis, and spermatogenesis. Proc Natl Acad Sci U S A. 111:E2851–E2857. 2014. View Article : Google Scholar : PubMed/NCBI
26	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI