Till startsida
University of Gothenburg
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Group David Bryder

Research Summary

Hematopoietic (blood) stem cells (HSCs) represent an extremely rare, but highly potent cell type located in the bone marrow. Two main functional attributes associate with HSCs; an ability to produce all of the different types of blood cells, and their ability to give rise to new stem cells. These two properties enable an individual to maintain blood cell formation over a lifetime from a relatively few number of cells. It is also these properties that are utilized in the clinical use of bone marrow transplantation, in which HSCs rebuild a completely new blood system.
Our research focus on how HSCs and their immediate offspring are regulated in situations such as infections, stress, aging and leukemia. Although HSCs are associated with a fairly clear functional definition regarding their developmental and self-renewal potential, all HSCs do not behave the same. A striking example is the situation during fetal development. Here, HSCs can give rise to different types of specialized blood cells that cannot be regenerated from HSCs found in adult individuals. Similarly, we have shown that HSCs found in older individuals differ from HSCs found in younger subjects, including a dramatically reduced ability to develop into blood cells involved in adaptive immunity (T and B cells).
Our goal is to understand, at cellular and molecular levels, what controls HSCs and the fate of other immature blood cells. Traditionally, such evaluations have been made using transplantation-based models, but recent and ongoing studies, including from our laboratory, have shown that HSC function in this setting is fundamentally different from normal HSC function. We believe such enhanced knowledge can be used both preventively and therapeutically, by being able to expand the use of stem cell transplantation as a therapy, but also in the development of stem cell-based therapies that do not involve direct transplantation.

Research Tools and Resources

We use advanced cell sorting and a range of cellular and newer molecular biology techniques, including next-generation sequencing and Cas9/Crispr-based approaches, many which are applied at the level of single cells. We apply and develop novel transgenic mouse models.

Selected Publications

  1. Wahlestedt M, Ladopoulos V, Hidalgo I, Sanchez Castillo M, Hannah R, Säwén P, Wan H, Dudenhöffer-Pfeifer M, Magnusson M, Norddahl GL, Göttgens B, Bryder D. Critical modulation of hematopoietic lineage fate by Hepatic Leukemia Factor. Cell Rep. 2017 Nov 21;21(8):2251-2263.
  2. Wahlestedt M, Erlandsson E, Kristiansen T, Lu R, Brakebusch C, Weissman IL, Yuan J, Martin-Gonzalez J, Bryder D. Clonal reversal of ageing-associated stem cell lineage bias via a pluripotent intermediate. Nat Commun. 2017 Feb 22;8:14533.
  3. Säwén P, Lang S, Mandal P, Rossi DJ, Soneji S, Bryder D. Mitotic History Reveals Distinct Stem Cell Populations and Their Contributions to Hematopoiesis. Cell Rep. 2016 Mar 29;14(12):2809-18.
  4. Ugale A, Norddahl GL, Wahlestedt M, Säwén P, Jaako P, Pronk CJ, Soneji S, Cammenga J, Bryder D. Hematopoietic stem cells are intrinsically protected against MLL-ENL-mediated transformation. Cell Rep. 2014 Nov 20;9(4):1246-55.
  5. Bryder D, Rossi DJ, Weissman IL. Hematopoietic stem cells: the paradigmatic tissue-specific stem cell. Am J Pathol. 2006 Aug;169(2):338-46.
Page Manager: Ulrika Lantz Carlsson|Last update: 12/5/2017

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