Belderbos group

Group leader: Dr. Mirjam Belderbos

Phone 088-9727272

Email m.e.belderbos@prinsesmaximacentrum.nl

Hematopoietic stem cells

Hematopoietic stem cells (HSCs) are responsible for the production of all mature blood cell types throughout life, generating billions of mature blood cells each day. Aside from their role in homeostatic hematopoiesis, HSCs are crucial to regenerate the hematopoietic system upon myeloablative challenge, such as chemotherapy or transplantation.

Understanding human hematopoietic stem cell biology requires innovative research in human subjects Dr. Mirjam Belderbos - Group leader

Single-cell analysis of bone marrow regeneration in humans

To understand how a relatively small number of HSCs (re-)generate the entire hematopoietic system, our group integrates state-of-the-art single cell methods with clinical data and primary patient samples. The lab is currently investigating how transplanted HSCs regenerate each of the blood lineages, and whether/how transplantation affects the composition and functional integrity of the stem cell pool. In addition, we aim to determine how common transplantation-related exposures, such as proliferative stress, inflammation and ageing, affect stem cell function. Technologies used include single-cell RNA sequencing, CITE-seq, RNAFlex, and spatial transcriptomics. Understanding how transplanted HSCs regenerate the hematopoietic system is relevant to improve the outcome of HCT and will contribute to stem cell-based theraies in general.

Long-term integrity of hematopoiesis in stem cell transplantation survivors

HCT is the first and most commonly applied type of stem cell therapy in humans. Every year, over 40.000 patients undergo HCT, as a curative therapy for various diseases, including high-risk leukemia. Due to improved treatment protocols, the number of HCT survivors and their life expectancy continue to increase. It is yet unknown how tranplanted HSCs maintain their life-long integrity. To address this question, our lab leads an ongoing clinical/translational trial in long-term HCT survivors. By integrating clinical data and molecular features of hematopoiesis in these patients, we aim to define critical determinants that guide HSC longevity after HCT, which might be targeted therapeutically.

Origins of pediatric bone marrow failure and myelodysplasia

Our group also focuses on the origins and mechanisms of HSC dysfunction in pediatric bone marrow failure. Using single-cell sequencing strategies, we aim to define which hematopoietic cell populations are involved in the pathogenesis of bone marrow failure and myelodysplasia, and characterize the genomic pathways active within these cells. Ultimately, we envision that this will contribute to novel strategies to predict the occurrence of bone marrow failure/myelodysplasia, allowing for targeted intervention and preventive measures.

Grants and awards

Grants

How is blood (re-)made? Regeneration of human hematopoietic stem cells after transplantation (RESTART) - European Research Council (2024-2029).
Single-cell multiomics to dissect the impact of donor source on hematopoietic regeneration in human recipients - Landsteiner Foundation (2024-2029).
Can stem cells live 130 years? Long-term hematopoietic integrity in pediatric transplantation survivors - KiKa (2021-2025).
Population dynamics of blood in human hematopoietic stem cell transplantation recipients (with Van Boxtel group- European Hematology Associaton (2020-2024).
Tracing the clonal dynamics of human hematopoiesis using single-cell analysis of genomic mutations (with Van Boxtel group) - NWO Veni (2020-2024).

Awards
Swammerdam Award, Dutch Society for Hematology (2022) - News article

Key publications

1. De Kanter JK, Peci F, Bertrums E, Rosendahl Huber A, van Leeuwen A, van Roosmalen MJ, Manders F, Verheul M, Oka R, Brandsma AM, Bierings M, Belderbos M, van Boxtel R: Antiviral treatment causes a unique mutational signature in cancers of transplantation recipients. Cell Stem Cell 2021;28(10):1726-1739.

2. Jung JM, Ching W, Baumdick ME, Hofmann-Sieber H, Bosse JB, Koyro T, Möller KJ, Wegner L, Niehrs A, Russu K, Ohms M, Zhang W, Ehrhardt A, Duisters K, Spierings E, Hölzemer A, Körner C, Jansen SA, Peine S, Königs I, Lütgehetmann M, Perez D, Reinshagen K, Lindemans CA, Altfeld M, Belderbos M, Dobner T, Bunders MJ: KIR3DS1 directs NK-cell-mediated protection against human adenovirus infections. Science Immunol. 2021;6(63):eabe2942.

3. Middelkamp S, Manders F, Peci F, van Roosmalen MJ, González DM, Bertrums EJM, van der Werf I, Derks LLM, Groenen NM, Verheul M, Trabut L, Pleguezuelos-Manzano C, Brandsma AM, Antoniou E, Reinhardt D, Bierings M, Belderbos ME, van Boxtel R: Comprehensive single-cell genome aalysis at nucleotide resolution using the PTA analysis toolbox. Cell Genom. 2023;3(9):100389.

4. Belderbos ME, Gennery AR, Dvorak CC, Blok HJ, Eikema DJ, Silva JMF, Veys P, Neven B, Buckley R, Cole T, Cowan MJ, Goebel WS, Hoenig M, Kuo CY, Stiehm ER, Wynn R, Bierings M; Inborn Errors Working Party of the European Group for Blood and Marrow Transplantation and the Primary Immune Deficiency Treatment Consortium: Outcome of domino hematopoietic stem cell transplantation in human subjects: An international case series. J Allergy Clin Immunol. 2018 Nov;142(5):1628-1631.e4.

5. Belderbos ME, Koster T, Ausema B, Jacobs S, Sowdagar S, Zwart E, de Bont E, de Haan G, Bystrykh LV.: Clonal selection and asymmetric distribution of human leukemia in murine xenografts revealed by cellular barcoding. Blood. 2017 Jun 15;129(24):3210-3220.

Our team

Our group consists of a multidisciplinary team, with wet-lab biologists, bioinformaticians and clinical researchers. The group is led by dr. Mirjam Belderbos, MD, PhD. Next to her scientific activities, dr. Belderbos works as a pediatric oncologist in hematopoietic stem cell transplantation. Core values in our group are collaboration, curiosity and clinical impact.