Research Groups

Ageing Biology and Stem Cells

The general scope of studies in the Laboratory of Ageing Biology and Stem Cells is to further improve our understanding of mechanisms that specify normal hematopoietic stem cell functioning.

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  • Gerald de Haan Visit

    Scientific Director, Group Leader of the Laboratory of Ageing Biology and Stem Cells

    Research fields

    Hematopoietic stem cells, aging, leukemia, genetics, epigenetics

    Research Associates
    Leonid Bystrykh
    Postdoctoral Fellows
    Mirjam Belderbos
    PhD Students
    Sonja Buisman
    Sabrina Jacobs
    Daniëlle Luinenburg
    Natalia Skinder
    Arthur Flohr Svendsen
    Jason Yang
    Ellen Weersing
  • The group is interested in the unique genetic and epigenetic program that distinguishes stem cells from non-stem cells. De Haan’s group uses state-of-the art genomic tools to search for common molecular events in stem cells at distinct phases in hematopoietic development and aging. The team studies how stem cells can be transplanted, and which mechanisms ensure their proper homing and subsequent engraftment to the bone marrow after transplantation. Stem cells are defined by their ability to self-renew and their ability to differentiate into all lineages within a tissue. The group is addressing how stem cell self-renewal alters with age, and how enhance stem cell renewal can be exploitated in stem cell expansion protocols in vivo and in vitro.

    • Belderbos ME, Jacobs S, Koster TK, Ausema A, Weersing E, Zwart E, de Haan G, Bystrykh LV. (2019) Donor-to-Donor Heterogeneity in the Clonal Dynamics of Transplanted Human Cord Blood Stem Cells in Murine Xenografts. Biology of Blood and Marrow Transplantion.  
    • Buisman SC, de Haan G. (2019) Epigenetic Changes as a Target in Aging Haematopoietic Stem Cells and Age-Related Malignancies. Cells.
    • Jacobs S, Ausema A, Zwart E, Weersing E, Kingma MJ, El Menshawi YAS, de Haan G, Bystrykh LV, Belderbos ME. (2019) Quantitative distribution of patient-derived leukemia clones in murine xenografts revealed by cellular barcodes. Leukemia.
    • Ackermann T, Hartleben G, Müller C, Mastrobuoni G, Groth M, Sterken BA, Zaini MA, Youssef SA, Zuidhof HR, Krauss SR, Kortman G, de Haan G, de Bruin A, Wang ZQ, Platzer M, Kempa S, Calkhoven CF. (2019) C/EBPβ-LIP induces cancer-type metabolic reprogramming by regulating the let-7/LIN28B circuit in mice. Communications Biology.
    • Wojtowicz EE, Broekhuis MJC, Weersing E, Dinitzen A, Verovskaya E, Ausema A, Ritsema M, Zwart E, de Haan G, Bystrykh LV. (2019) MiR-125a enhances self-renewal, lifespan, and migration of murine hematopoietic stem and progenitor cell clones. Scientific Reports.
    • Jung J, Buisman SC, Weersing E, Dethmers-Ausema A, Zwart E, Schepers H, Dekker MR, Lazare SS, Hammerl F, Skokova Y, Kooistra SM, Klauke K, Poot RA, Bystrykh LV, de Haan G. (2019) CBX7 Induces Self-Renewal of Human Normal and Malignant Hematopoietic Stem and Progenitor Cells by Canonical and Non-canonical Interactions. Cell Reports.
    • Han Y, Eipel M, Franzen J, Sakk V, Dethmers-Ausema B, Yndriago L, Izeta A, de Haan G, Geiger H, Wagner W. (2018) Epigenetic age-predictor for mice based on three CpG sites. eLife.
    • de Haan G, Lazare S. (2018) Aging of hematopoietic stem cells. Blood.
    • Belderbos M, Bystrykh L, de Haan G. (2018) Left or right? Directions to stem cell engraftment. J Exp Med.
    • Martín-Pardillos A, Tsaalbi-Shtylik A,  Chen S,  Lazare S, van Os RP, Dethmers-Ausema A, Borhan Fakouri N, Bosshard M, Aprigliano R,  van Loon B, Salvatori DCF , Hashimoto K, Dingemanse-van der Spek C, Moriya M, Rasmussen LJ, de Haan G, Raaijmakers MHGP and de Wind N (2017) Genomic and functional integrity of the hematopoietic system requires tolerance of oxidative DNA lesions. Blood.
    • Lazare S, Ausema A, Reijne AC, van Dijk G, van Os R, de Haan G.(2017) Lifelong dietary intervention does not affect hematopoietic stem cell function. Experimental Hematology.
    • Belderbos ME, Koster T, Ausema B, Jacobs S, Sowdagar S, Zwart E, de Bont E, de Haan G and Bystrykh LV. (2017) Clonal selection and asymmetric distribution of human leukemia in murine xenografts revealed by cellular barcoding. Blood.
    • Jung JJ, Buisman SC, de Haan G. (2017) Do hematopoietic stem cells get old? Leukemia.
    • Wojtowicz EE, Lechman ER, Hermans KG, Schoof EM, Wienholds E, Isserlin R, van Veelen PA, Broekhuis MJC, Janssen GMC, Trotman-Grant A, Dobson2 SM, Krivdova G, Elzinga J, Kennedy J, Gan O, Sinha O, Ignatchenko V, Kislinger T, Weersing E, Alemdehy MF,  de Looper HWJ, Bader GD, Ritsema M,  Erkeland SJ, Bystrykh LV, Dick2 JE and de Haan G. (2016) Ectopic miR-125a Expression Induces Long-Term Repopulating Stem Cell Capacity in Mouse and Human Hematopoietic Progenitors. Cell Stem Cell.
    • Russo Kraus S, de Haan G. (2016) Epigenetic perturbations in aging stem cells. Mamm Genome.
    • Jung J, Buisman S, de Haan G. (2016) Hematopoiesis during development, aging, and disease. Experimental Hematology.
    • Pringle S, Maimets M, van der Zwaag M, Stokman MA, van Gosliga D, Zwart E, Witjes MJ, de Haan G, van Os R, Coppes RP. (2016) Human Salivary Gland Stem Cells Functionally Restore Radiation Damaged Salivary Glands. Stem Cells.
    • Maimets M, Rocchi C, Bron R, Kuipers J, Giepmans BN, Vries RGJ, Clever H, de Haan G, van Os R, Coppes R. (2015) Long-term in vitro expansion of salivary gland stem cells driven by Wnt signals. Stem Cell Reports.
    • Brugman MH, Wiekmeijer A, van Eggermond MCJA, Wolvers-Tettero ILM, Langerak AW, de Haas EFE, Bystrykh LV, van Rood JJ, de Haan G, Fibbe WE, Staal FJT. (2015) Development of a diverse human T cell repertoire despite stringent restriction of hematopoietic clonality in the thymus. PNAS.
    • Maimets M, Bron R, de Haan G, van Os R, Coppes RP. (2015) Similar ex vivo expansion and post-irradiation regenerative potential of juvenile and aged salivary gland stem cells. Radiotherapy and Oncology.
    • Artandi SE, Blau HM, de Haan G, Geiger H, Goodell MA, Jones L, Levine RL, Muñoz-Cánoves P, Rodewald HR, Wagers A, Wang ZQ, Yamashita Y. (2015) Stem Cells and Aging: What's Next? Cell Stem Cell.
    • Nanduri LSY, Baanstra M, Faber H, Rocchi C, Zwart E, de Haan G, van Os R, Coppes RP. (2014) Purification and ex vivo expansion of fully functional salivary gland stem cells. Stem Cell Reports
    • Klauke K, Broekhuis MJ, Weersing E, Dethmers-Ausema A, Ritsema M, González MV, Zwart E, Bystrykh LV, de Haan G. (2014) Tracing Dynamics and Clonal Heterogeneity of Cbx7-Induced Leukemic Stem Cells by Cellular Barcoding. Stem Cell Reports.
    • Prick J, de Haan G, Green AR, Kent DG. (2014) Clonal heterogeneity as a driver of disease variability in the evolution of myeloproliferative neoplasms. Experimental Hematology.
    • Brendel C, Goebel B, Daniela A, Brugman M, Kneissl S, Schwäble J, Kaufmann KB, Müller-Kuller U, Kunkel H, Chen-Wichmann L, Abel T, Serve H, Bystrykh L, Buchholz CJ, Grez M. (2014) CD133-targeted Gene Transfer Into Long-term Repopulating Hematopoietic Stem Cells. Molecular Therapy.
    • Korthuis PM, Berger G, Bakker B, Rozenveld-Geugien M, Jaques J, de Haan G, Schuringa JJ, Vellenga E, Schepers H. (2014) CITED2-mediated human hematopoietic stem cell maintenance is critical for acute myeloid leukemia. Leukemia.
    • Lazare SS, Wojtowicz EE, Bystrykh LV, de Haan G. (2014) microRNAs in hematopoiesis. Experimental Cell Research.
    • Buschmann T, Zhang R, Brash DE, Bystrykh LV. (2014) Enhancing the detection of barcoded reads in high throughput DNA sequencing data by controlling the false discovery rate. BMC Bioinformatics.
    • Wojtowicz EE, Walasek MA, Broekhuis MJ, Weersing E, Ritsema M, Ausema A, Bystrykh LV, de Haan G. (2014) MicroRNA-125 family members exert a similar role in the regulation of murine hematopoiesis. Experimental Hematology.
    • Bystrykh LV, de Haan G, Verovskaya E. (2014) Barcoded vector libraries and retroviral or lentiviral barcoding of hematopoietic stem cells. Methods Molecular Biology.
    • van Os R, de Haan G. (2014) Stem Cells, from basic research to therapy, Volume 2, chapter 1: Dynamics and aging of hematopoietic stem cells. ISBN 978-1-4822-1983-8
    • de Kruijf EJ, Alkemade GM, van Os R, Fibbe WE, van Pel M. (2014) Peripheral blood hematopoietic stem and progenitor cell frequency is unchanged in patients with alpha-1-antitrypsin deficiency. International  Journal of Hematology.
    • Dykstra B, Bystrykh LV. (2014) No monkeying around: clonal tracking of stem cells and progenitors in the macaque. Cell Stem Cell.
    • Verovskaya E, Broekhuis MJ, Zwart E, Weersing E, Ritsema M, Bosman LJ, van Poele T, de Haan G, Bystrykh LV. (2014) Asymmetry in skeletal distribution of mouse hematopoietic stem cell clones and their equilibration by mobilizing cytokines. The Journal of Experimental Medicine.
    • Verovskaya E , de Haan G. (2013) Non-canonical Wnt comes of age in hematopoietic stem cells. Cell Stem Cell.
    • Duran AL, Potter P, Wells S, Kirkwood T, von Zglinicki T, McArdle A, Scudamore C, Meng QJ, de Haan G, Corcoran A, Bellantuono I. (2013) Shared Ageing Research Models (ShARM): a new facility to support ageing research. Biogerontology.
    • Nanduri LS, Lombaert IM, van der Zwaag M, Faber H, Brunsting JF, van Os RP, Coppes RP. (2013) Salisphere derived c-Kit+ cell transplantation restores tissue homeostasis in irradiated salivary gland. Radiotherapy and Oncology.
    • Verovskaya E, Broekhuis MJ, Zwart E, Ritsema M, van Os R, de Haan G, Bystrykh LV. (2013) Heterogeneity of young and aged murine hematopoietic stem cells revealed by quantitative clonal analysis using cellular barcoding. Blood.
    • Smit JK, Faber H, Niemantsverdriet M, Baanstra M, Bussink J, Hollema H, van Os RP, Plukker JT, Coppes RP. (2013) Prediction of response to radiotherapy in the treatment of esophageal cancer using stem cell markers. Radiotherapy and Oncology.
    • Geiger H, de Haan G and Florian MC. (2013) The ageing hematopoietic stem cell compartment. Nature Reviews Immunology.
    • Klauke K, Radulović V, Broekhuis M, Weersing E, Zwart E, Olthof S, Ritsema M, Bruggeman S, Wu X, Helin K, Bystrykh L, de Haan G. (2013) Polycomb Cbx family members mediate the balance between haematopoietic stem cell self-renewal and differentiation. Nature Cell Biology.
    • Glauche I et al. (2013) Stem cell clonality -- theoretical concepts, experimental techniques, and clinical challenges. Blood Cells, Molecules & Diseases.
    • Pringle S, Van Os R, Coppes RP. (2013) Concise review: Adult salivary gland stem cells and a potential therapy for xerostomia. Stem Cells.
    • Radulović V, de Haan G, Klauke K. (2013) Polycomb-group proteins in hematopoietic stem cell regulation and hematopoietic neoplasms. Leukemia.
    • Huls G, van Es J, Clevers H, de Haan G, van Os R. (2013) Loss of Tcf7 diminishes hematopoietic stem/progenitor cell function. Leukemia.
    • Walasek MA, Bystrykh LV, Olthof S, de Haan G, van Os R. (2013) Sca-1 is an early-response target of histone deacetylase inhibitors and marks hematopoietic cells with enhanced function. Experimental Hematology.
    • Bystrykh LV, Verovskaya E, Zwart E, Broekhuis M, de Haan G. (2012) Counting stem cells: methodological constraints. Nature Methods.
    • Gerrits A, Walasek MA, Olthof S, Weersing E, Ritsema M, Zwart E, van Os R, Bystrykh LV, de Haan G. (2011) Genetic screen identifies microRNA cluster 99b/let-7e/125a as a regulator of primitive hematopoietic cells. Blood.
    • Dykstra B, Olthof S, Schreuder J, Ritsema M, de Haan G. (2011) Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells. The Journal of Experimental Medicine.
    • Woolthuis CM, de Haan G, Huls G. (2011) Aging of hematopoietic stem cells: Intrinsic changes or micro-environmental effects?. Current Opinion in Immunology.
    • Klauke K, de Haan G. (2011) Polycomb group proteins in hematopoietic stem cell aging and malignancies. International Journal of Hematology.
    • Rizo A, Horton SJ, Olthof S, Dontje B, Ausema A, van Os R, van den Boom V, Vellenga E, de Haan G, Schuringa JJ. (2010) BMI1 collaborates with BCR-ABL in leukemic transformation of human CD34+ cells. Blood.
    • Gerrits A, Dykstra B, Kalmykowa OJ, Klauke K, Verovskaya E, Broekhuis MJ, de Haan G, Bystrykh LV. (2010) Cellular barcoding tool for clonal analysis in the hematopoietic system. Blood.
    • Gerrits A, Li Y, Tesson BM, Bystrykh LV, Weersing E, Ausema A, Dontje B, Wang X, Breitling R, Jansen RC, de Haan G. (2009) Expression quantitative trait loci are highly sensitive to cellular differentiation state. PLoS Genetics.
    • van Os R, de Haan G, Dykstra BJ. (2009) Hematopoietic stem cell quiescence: yet another role for p53. Cell Stem Cell.
    • Breitling R, Li Y, Tesson BM, Fu J, Wu C, Wiltshire T, Gerrits A, Bystrykh LV, de Haan G, Su AI, Jansen RC. (2008) Genetical genomics: spotlight on QTL hotspots. PLoS Genetics.
    • Lombaert IM, Brunsting JF, Wierenga PK, Kampinga HH, de Haan G, Coppes RP. (2008) Keratinocyte growth factor prevents radiation damage to salivary glands by expansion of the stem/progenitor pool. Stem Cells.
    • Lombaert IM, Brunsting JF, Wierenga PK, Faber H, Stokman MA, Kok T, Visser WH, Kampinga HH, de Haan G, Coppes RP. (2008) Rescue of salivary gland function after stem cell transplantation in irradiated glands. PLoS One.
    • Rizo A, Dontje B, Vellenga E, de Haan G, Schuringa JJ. (2008) Long-term maintenance of human hematopoietic stem/progenitor cells by expression of BMI1. Blood.
    • Dykstra B, de Haan G. (2008) Hematopoietic stem cell aging and self-renewal. Cell and tissue research.
    • van Os R, Kamminga LM, Ausema A, Bystrykh LV, Draijer DP, van Pelt K, Dontje B, de Haan G. (2007) A Limited role for p21Cip1/Waf1 in maintaining normal hematopoietic stem cell functioning. Stem Cells.
    • Rizo A, Vellenga E, de Haan G, Schuringa JJ. (2006) Signaling pathways in self-renewing hematopoietic and leukemic stem cells: do all stem cells need a niche?. Human molecular genetics.
    • Kamminga LM, de Haan G. (2006) Cellular memory and hematopoietic stem cell aging. Stem Cells.
    • Kamminga LM, Bystrykh LV, de Boer A, Houwer S, Douma J, Weersing E, Dontje B, de Haan G. (2006) The Polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion. Blood.
    • Bystrykh L, Weersing E, Dontje B, Sutton S, Pletcher MT, Wiltshire T, Su AI, Vellenga E, Wang J, Manly KF, Lu L, Chesler EJ, Alberts R, Jansen RC, Williams RW, Cooke MP, de Haan G. (2005) Uncovering regulatory pathways that affect hematopoietic stem cell function using 'genetical genomics'. Nature genetics.
    • de Haan G, Weersing E, Dontje B, van Os R, Bystrykh LV, Vellenga E, Miller G. (2003) In vitro generation of long-term repopulating hematopoietic stem cells by FGF-1. Developmental Cell.
    • Geiger H, True JM, de Haan G, Van Zant G. (2001) Age- and stage-specific regulation patterns in the hematopoietic stem cell hierarchy. Blood.
    • de Haan G, Van Zant G. (1999) Dynamic changes in mouse hematopoietic stem cell numbers during aging. Blood.
    • De Haan G, Van Zant G. (1999) Genetic analysis of hemopoietic cell cycling in mice suggests its involvement in organismal life span. FASEB Journal.
    • de Haan G, Gelman R, Watson A, Yunis E, Van Zant G. (1998) A putative gene causes variability in lifespan among genotypically identical mice. Nature Genetics.
    • de Haan G and Van Zant G. (1997) Intrinsic and extrinsic control of hemopoietic stem cell numbers: mapping of a stem cell gene. Journal of Experimental Medicine.
  • Aleksandra Rizo-Crcareva
    Senior Director, Johnson & Johnson, New York, US

    Alice Gerrits
    Clinical Chemist, Isala Hospital Zwolle, the Netherlands

    Edyta Wojtowicz
    Postdoctoral fellow Karolinska Institute, Stockholm, Sweden

    Evgenia Verovskaya
    Postdoctoral Fellow, University of California, San Fransisco, US

    Johannes Jung
    Hematologist at University Hospital Freiburg, Germany

    Karin Klauke
    Postdoctoral Fellow, ERIBA, Groningen, the Netherlands

    Marta Walasek
    Research Scientist, Stem Cell Technologies, Vancouver, Canada

    Sara Russo Krauss
    Clinical Research assistant, Centre for Research in Intensive Care, Copenhagen, Denmark

    Seka Lazare
    postdoctoral fellow, La Jolla Institute for Allergy and Immunology, San Diego, CA

    Visnja Radulovic
    Postdoctoral Fellow, Lund University, Sweden

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