Hideyuki Oguro

Assistant Professor
Department of Cell Biology

Contact

Phone: 860-679-6629
Email: oguro@uchc.edu
Office: E5040

UConn Health
263 Farmington Avenue
Farmington, CT 06030

Research Interests

My research concerns mechanisms that regulate hematopoietic stem cells, and investigates how in conditions where more blood is needed, hormonal signals stimulate the proliferation and mobilization of these stem cells to make more blood cells. In a recent paper (J. Clinical Investigation, 2017, 127: 3392-2401), we demonstrated that two endogenous estrogen receptor ligands, estradiol and 27-hydroxycholesterol, differentially induce proliferation and mobilization of hematopoietic stem cells, respectively. This hormonal regulation is particularly important during pregnancy when maternal blood expands rapidly (figure adopted from Frontiers in Endocrinology, 2019, 10:204), and can lead to new strategies to promote hematopoietic regeneration and to enhance mobilization of stem cells into the bloodstream for transplantation. An additional focus of my research is to generate hematopoietic stem cells from human induced pluripotent stem cells by mimicking their developmental process.

Publications

Oguro H. The Roles of Cholesterol and Its Metabolites in Normal and Malignant Hematopoiesis. Front Endocrinol (Lausanne). 2019;10:204doi: 10.3389/fendo.2019.00204. eCollection 2019. Review. PubMed PMID: 31001203; PubMed Central PMCID: PMC6454151.

Oguro H. Generation of Hematopoietic Stem and Progenitor Cells from Human Pluripotent Stem Cells. Methods Mol Biol. 2019;2048:245-257doi: 10.1007/978-1-4939-9728-2_19. PubMed PMID: 31396942.

Oguro H, McDonald JG, Zhao Z, Umetani M, Shaul PW, Morrison SJ. 27-Hydroxycholesterol induces hematopoietic stem cell mobilization and extramedullary hematopoiesis during pregnancy. J Clin Invest. 2017 Sep 1;127(9):3392-3401doi: 10.1172/JCI94027. Epub 2017 Aug 7. PubMed PMID: 28783041; PubMed Central PMCID: PMC5669562.

Acar M, Kocherlakota KS, Murphy MM, Peyer JG, Oguro H, Inra CN, Jaiyeola C, Zhao Z, Luby-Phelps K, Morrison SJ. Deep imaging of bone marrow shows non-dividing stem cells are mainly perisinusoidal. Nature. 2015 Oct 1;526(7571):126-30doi: 10.1038/nature15250. Epub 2015 Sep 23. PubMed PMID: 26416744; PubMed Central PMCID: PMC4850557.

Nakada D, Oguro H, Levi BP, Ryan N, Kitano A, Saitoh Y, Takeichi M, Wendt GR, Morrison SJ. Oestrogen increases haematopoietic stem-cell self-renewal in females and during pregnancy. Nature. 2014 Jan 23;505(7484):555-8doi: 10.1038/nature12932. PubMed PMID: 24451543; PubMed Central PMCID: PMC4015622.

Nakashima T, Liu T, Yu H, Ding L, Ullenbruch M, Hu B, Wu Z, Oguro H, Phan SH. Lung bone marrow-derived hematopoietic progenitor cells enhance pulmonary fibrosis. Am J Respir Crit Care Med. 2013 Oct 15;188(8):976-84doi: 10.1164/rccm.201303-0479OC. PubMed PMID: 24010731; PubMed Central PMCID: PMC3826283.

Oguro H, Ding L, Morrison SJ. SLAM family markers resolve functionally distinct subpopulations of hematopoietic stem cells and multipotent progenitors. Cell Stem Cell2013 Jul 3;13(1):102-16doi: 10.1016/j.stem.2013.05.014. PubMed PMID: 23827712; PubMed Central PMCID: PMC3736853.

Oguro H, Yuan J, Tanaka S, Miyagi S, Mochizuki-Kashio M, Ichikawa H, Yamazaki S, Koseki H, Nakauchi H, Iwama A. Lethal myelofibrosis induced by Bmi1-deficient hematopoietic cells unveils a tumor suppressor function of the polycomb group genes. J Exp Med. 2012 Mar 12;209(3):445-54doi: 10.1084/jem.20111709. Epub 2012 Feb 20. PubMed PMID: 22351929; PubMed Central PMCID: PMC3302226.

Yuan J, Takeuchi M, Negishi M, Oguro H, Ichikawa H, Iwama A. Bmi1 is essential for leukemic reprogramming of myeloid progenitor cells. Leukemia. 2011 Aug;25(8):1335-43doi: 10.1038/leu.2011.85. Epub 2011 Apr 29. PubMed PMID: 21527932.

Konuma T, Nakamura S, Miyagi S, Negishi M, Chiba T, Oguro H, Yuan J, Mochizuki-Kashio M, Ichikawa H, Miyoshi H, Vidal M, Iwama A. Forced expression of the histone demethylase Fbxl10 maintains self-renewing hematopoietic stem cells. Exp Hematol. 2011 Jun;39(6):697-709.e5doi: 10.1016/j.exphem.2011.03.008. Epub 2011 Apr 12. PubMed PMID: 21540074.

Chiba T, Seki A, Aoki R, Ichikawa H, Negishi M, Miyagi S, Oguro H, Saraya A, Kamiya A, Nakauchi H, Yokosuka O, Iwama A. Bmi1 promotes hepatic stem cell expansion and tumorigenicity in both Ink4a/Arf-dependent and -independent manners in mice. Hepatology2010 Sep;52(3):1111-23doi: 10.1002/hep.23793. PubMed PMID: 20648475.

Konuma T, Oguro H, Iwama A. Role of the polycomb group proteins in hematopoietic stem cells. Dev Growth Differ. 2010 Aug;52(6):505-16doi: 10.1111/j.1440-169X.2010.01191.x. Review. PubMed PMID: 20646023.

Sugawara T, Oguro H, Negishi M, Morita Y, Ichikawa H, Iseki T, Yokosuka O, Nakauchi H, Iwama A. FET family proto-oncogene Fus contributes to self-renewal of hematopoietic stem cells. Exp Hematol. 2010 Aug;38(8):696-706doi: 10.1016/j.exphem.2010.04.006. Epub 2010 Apr 20. PubMed PMID: 20412831.

Koizumi T, Negishi M, Nakamura S, Oguro H, Satoh K, Ichinose M, Iwama A. Depletion of Dnmt1-associated protein 1 triggers DNA damage and compromises the proliferative capacity of hematopoietic stem cells. Int J Hematol2010 May;91(4):611-9doi: 10.1007/s12185-010-0563-3. Epub 2010 Apr 14. PubMed PMID: 20387133.

Oguro H, Yuan J, Ichikawa H, Ikawa T, Yamazaki S, Kawamoto H, Nakauchi H, Iwama A. Poised lineage specification in multipotential hematopoietic stem and progenitor cells by the polycomb protein Bmi1. Cell Stem Cell. 2010 Mar 5;6(3):279-86doi: 10.1016/j.stem.2010.01.005. PubMed PMID: 20207230.

Matsuoka S, Oike Y, Onoyama I, Iwama A, Arai F, Takubo K, Mashimo Y, Oguro H, Nitta E, Ito K, Miyamoto K, Yoshiwara H, Hosokawa K, Nakamura Y, Gomei Y, Iwasaki H, Hayashi Y, Matsuzaki Y, Nakayama K, Ikeda Y, Hata A, Chiba S, Nakayama KI, Suda T. Fbxw7 acts as a critical fail-safe against premature loss of hematopoietic stem cells and development of T-ALL. Genes Dev. 2008 Apr 15;22(8):986-91doi: 10.1101/gad.1621808. Epub 2008 Mar 26. PubMed PMID: 18367647; PubMed Central PMCID: PMC2335330.

Oguro H, Iwama A. Life and death in hematopoietic stem cells. Curr Opin Immunol. 2007 Oct;19(5):503-9doi: 10.1016/j.coi.2007.05.001. Epub 2007 Jul 6. Review. PubMed PMID: 17618101.

Oyama T, Harigaya K, Muradil A, Hozumi K, Habu S, Oguro H, Iwama A, Matsuno K, Sakamoto R, Sato M, Yoshida N, Kitagawa M. Mastermind-1 is required for Notch signal-dependent steps in lymphocyte development in vivo. Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9764-9doi: 10.1073/pnas.0700240104. Epub 2007 May 29. PubMed PMID: 17535917; PubMed Central PMCID: PMC1887568.

Oguro H, Iwama A, Morita Y, Kamijo T, van Lohuizen M, Nakauchi H. Differential impact of Ink4a and Arf on hematopoietic stem cells and their bone marrow microenvironment in Bmi1-deficient mice. J Exp Med. 2006 Oct 2;203(10):2247-53doi: 10.1084/jem.20052477. Epub 2006 Sep 5. PubMed PMID: 16954369; PubMed Central PMCID: PMC2118102.

Miyagi S, Nishimoto M, Saito T, Ninomiya M, Sawamoto K, Okano H, Muramatsu M, Oguro H, Iwama A, Okuda A. The Sox2 regulatory region 2 functions as a neural stem cell-specific enhancer in the telencephalon. J Biol Chem. 2006 May 12;281(19):13374-81doi: 10.1074/jbc.M512669200. Epub 2006 Mar 16. PubMed PMID: 16547000.

Sakaguchi M, Shingo T, Shimazaki T, Okano HJ, Shiwa M, Ishibashi S, Oguro H, Ninomiya M, Kadoya T, Horie H, Shibuya A, Mizusawa H, Poirier F, Nakauchi H, Sawamoto K, Okano H. A carbohydrate-binding protein, Galectin-1, promotes proliferation of adult neural stem cells. Proc Natl Acad Sci U S A2006 May 2;103(18):7112-7doi: 10.1073/pnas.0508793103. Epub 2006 Apr 24. PubMed PMID: 16636291; PubMed Central PMCID: PMC1447526.

Iwama A, Oguro H, Negishi M, Kato Y, Nakauchia H. Epigenetic regulation of hematopoietic stem cell self-renewal by polycomb group genes. Int J Hematol. 2005 May;81(4):294-300doi: 10.1532/IJH97.05011. Review. PubMed PMID: 15914357.

Nakauchi H, Oguro H, Negishi M, Iwama A. Polycomb gene product Bmi-1 regulates stem cell self-renewal. Ernst Schering Res Found Workshop. 2005;(54):85-100doi: 10.1007/3-540-37644-5_6. PubMed PMID: 16080288.

Iwama A, Oguro H, Negishi M, Kato Y, Morita Y, Tsukui H, Ema H, Kamijo T, Katoh-Fukui Y, Koseki H, van Lohuizen M, Nakauchi H. Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1. Immunity. 2004 Dec;21(6):843-51doi: 10.1016/j.immuni.2004.11.004. PubMed PMID: 15589172.