Hematopoietic Stem Cells
	Sten Eirik W. Jacobsen Director of Center Professor of Stem Cell Biology Head of the Laboratory
Address:	Hematopoietic Stem Cell Laboratory Stem Cell Institute Lund Center for Stem Cell Biology and Cell Therapy BMC B-10 Klinikgatan 26 221 84, Lund, Sweden Tel: 46-46-222-4852 Fax: 46-46-2223600 E-mail: sten.Jacobsen@stemcell.lu.se

Main Research Topics Laboratory Members Selected Recent and Key Publications Link to Hematopoietic Stem Cell Laboratory

Main Research Topics Molecular regulation of hematopoiesis and hematopietic stem cell fate decisions Our research program is focused at identifying molecular mechanisms governing stem cell fate decisions and lineage development within the hematopoietic system. Towards this aim we are pursuing the following directions: 1. Advanced fluorescence activated cell sorting (FACS) is used to prospectively purify, and subsequently characterize novel subsets of mouse and human hematopoietic stem cells (HSC) in vitro as well as upon transplantation. 2. Identification and characterization of stem cells in patients with hematological malignancies, to investigate to what degree HSC rather than progenitors are the primary targets for malignant transformation, and to characterize the leukemic stem cell population responsible for maintaining the leukemia at the cellular and molecular level. Recently, we have demonstrated that the primary transformation in myelodysplastic syndromes (MDS) occurs at the level of a multipotent HSC. 3. Molecular regulation of HSC fate decisions. The importance of cytokine signaling, in particular the cytokine tyrosine kinase receptors flt3 and c-kit, as well as notch signalling, transcription factors and cell cycle regulators in regulation of HSC self renewal and lineage commitment is investigated through gene modification with viral vectors and in transgenic/knockout mouse models. 4. The potential ability of HSC to adapt non-hematopoietic cell fates is investigated in close collaboration with other research groups working in the areas of diabetes, neurodegenerative and cardiovascular diseases. The goal is to establish conclusively whether or not adult HSC might also have the plasticity to adapt non-hematopoietic fates, and if so explore the mechanisms for such plasticity. 5. Gene regulation and transcription control in cellular differentiation processes, primarily within the B lymphoid system. Mikael Sigvardsson who is an associate professor in immunology heads this research group. Laboratory Members Adolfsson, Jörgen, MSc, PhD student Anderson, Kristina, MD, PhD student Buza-Vidas, Natalija, PhD student Castor, Anders, MD, PhD student Fossum, Anna, MSc, Resarch engineer Gisler, Ramiro, PhD Gärdebring, Gunilla, Laboratory assistent Hultquist, Anne, MD, PhD, post doc Jacobsen, Sten Eirik W., MD, PhD, Professor, Head of department Jorup-Engström, Eva, Secretary Jensen, Christina, PhD student Jovinge, Stefan, MD, PhD, Senior scientist Lagergren, Anna, PhD student Liuba, Karina, MD, PhD student Ma, Zhi, MD, PhD, Research engineer Månsson, Robert, PhD student Nilsson, Lars, MD, PhD student Nygren, Jens, MSc, PhD student Pronk, Kees-Jan, MD, PhD student Sasaki, Yutaka, MD, PhD, post doc Sigvardsson, Mikael, PhD, Docent, Associate Professor, Director of studies Sitnicka, Ewa, MSc, PhD, Senior Scientist Smith, Emma, PhD student Taneera, Jalal, MSc, PhD student Thoren, Lina, Ph.D. student Tsapogas, Panagiotis, PhD student Wirén, Märta, Secretary Wittmann, Lilian, Laboratory assistent Yang, Liping, MD, PhD student Åstrand-Grundström, Ingbritt, Laboratory assistent 046 - 222 30 74 046 - 222 30 83 046 - 222 30 74 046 - 222 30 74 046 - 222 30 84 046 - 222 38 29 046 - 222 30 83 046 - 222 30 74 046 - 222 30 82 046 - 222 04 62 046 - 222 30 83 046 - 222 30 83 046 - 222 38 29 046 - 222 30 74 046 - 222 30 84 046 - 222 38 29 046 - 222 30 83 046 - 222 30 83 046 - 222 30 74 046 - 222 30 83 046 - 222 38 29 046 - 222 46 76 046 - 222 38 29 046 - 222 30 74 046 - 222 30 74 046 - 222 38 29 046 - 222 30 81 046 - 222 30 74 046 - 222 30 74 046 - 222 30 74 Selected Recent and Key Publications 1. Adolfsson J, Borge OJ, Bryder D, Theilgaard-Mönch K, Åstrand-Grundström I, Sitnicka E, Sasaki Y, Jacobsen SEW: Upregulation of flt3 expression within the bone marrow Lin-Sca1+kit+ stem cell compartment is accompanied by loss of self renewal capacity but sustained ability to reconstitute B and T lymphopoiesis. Immunity (Cell press) 15.659-669, 2001. 2. Björgvinsdóttir H, Bryder D, Sitnicka E, Rusterholz C, de Jong I, Olsson K, Karlsson S, Jacobsen SEW. Efficient oncoretroviral transduction of extended long-term culture-initiating cells and NOD/SCID repopulating cells: Enhanced reconstitution with gene-marked cells through an ex vivo expansion approach. Human Gene Therapy 13:1061-1073, 2002 3. Bryder D, Jacobsen SEW: Interleukin-3 supports expansion of multilineage long-term reconstituting activity following multiple stem cell selfrenewing divisions in vitro. Blood 96 1748-1755, 2000. 4. Bryder D, Ramsfjell V, Dybedal I, Theilgaard-Mönch K, Hogerkorp CM, Adolfsson J, Borge OJ, Jacobsen SEW: Self renewal of multipotent long-term reconstituting hematopoietic stem cells is negatively regulated by Fas and tumor necrosis factor receptor activation. J Exp Med 194:941-952, 2001. 5. Nilsson L, Åstrand-Grundström I, Anderson K, Arvidsson I, Hokland P, Bryder D, Kjeldsen L, Johansson B, Hellström-Lindberg E, Hast R, Jacobsen SEW: Involvement and functional impairment of the CD34+CD38-Thy1+ hematopoietic stem cell pool in myelodysplastic syndromes with trisomy 8. Blood 100:259-267, 2002 6. Nilsson L, Grundström IB, Arvidsson I, Jacobsson B, Hellström-Lindberg, Hast R, Jacobsen SEW: Isolation and characterization of hematopoietic progenitor/stem cells in 5q- myelodysplastic syndromes: Evidence for involvement at the hematopoietic stem cell level. Blood 96:2012-2021, 2000 7. Sigvardsson M, Clark D, Fitzsimmons D, Doyle M, Åkerblad P, Breslin T, Bilke S, Liu Y, Yeamans C, Hagman J. EBF and E2A proteins cooperate to activate the early B cell specific mb-1 promoter. Mol Cell Biol 22: 8539-8551, 2002. 8. Sitnicka E, Bryder D, Adolfsson J, Jacobsen SEW: Key role of flt3 ligand in generation of the common lymphoid progenitor but not in maintenance of the hematopoietic stem cell pool. Immunity (Cell press) 17:463-472, 2002 9. Smith M, Gisler R, Sigvardsson M: Cloning and characterisation of a promoter flanking the Early B-cell Factor gene suggests direct roles for E-proteins and auto-regulation in the control of EBF expression. Journal of Immunology 169:261-270, 2002 10. Åkerblad P, Lind U, Liberg D, Bamberg K, Sigvardsson M. Regulation of adipogenesis by O/E1 (Early- B cell Factor, Olf-1). Mol Cell Biol 22: 8015-8025, 2002. 11.Dybedal I, Yang L, Bryder D, Åstrand-Grundström I, Leandersson K, Jacobsen SEW: Human reconstituting hematopoietic stem cells upregulate Fas expression upon active cell cycling but remain resistant to Fas-induced suppression. Blood 102:118-126, 2003 12.Sitnicka E, Buza-Vidas N, Larsson S, Nygren JM, Liuba K, Jacobsen SEW: Human CD34+ hematopoietic stem cells capable of multilineage engrafting NOD/SCID mice express flt3: distinct flt3 and c-kit expression and response patterns on mouse and human hematopoietic stem cells. Blood 102:881-886, 2003 13. Sitnicka E, Brakebusch C, Martensson IL, Svensson M, Agace WW, Sigvardsson M, Buza-Vidas N, Cilio CM, Maraskovsky E, Peschon JJ, Jacobsen SEW: Complementary signaling through flt3 and interleukin-7 receptor ais indispensable for fetal and adult B cell genesis. Journal of Experimental Medicine, in press.