Robert Månsson group

The hematopoietic system is maintained through the continuous generation of new mature effector cells from self-renewing multipotent progenitors. A major challenge for the field is to understand mechanisms behind this differentiation process.

Our research mainly focuses around the developmental progression from stem and progenitor cells into mature B-lymphoid cells and the transcriptional networks that drive this process. We study this through a combination of in vivo models and cell- and molecular biology techniques.

Overall aim is to understand the differentiation process and through this increase our understanding of diseases that originate from developmental defects such as cancer and various immunodeficiencies.

Keywords: hematopoietic progenitor, B-cell development, transcriptional network, transcription factor, differentiation, interacting regulatory elements

Members

Robert Månsson, Group Leader, Assistant Professor.

He received his PhD in Stem Cell Biology from the Faculty of Medicine at Lund University in 2007. He then continued his research as a post doctorial fellow at University of California, San Diego. Since early 2012 he holds an assistant professor position at Karolinska Institutet. Phone: +46 (0)8 - 585 8623

Charlotte Gustafsson, PhD, Senior Lab Manager.

She received her PhD in Clinical Immunology from the Faculty of Health Sciences at Linköping University in 2007. Before starting at Karolinska Institutet in september 2012, she worked as a Research Scientist at AstraZeneca in Södertälje. Phone: +46 (0)8 - 585 826 76

Shabnam Kharazi, Postdoc. 

She got her PhD in Stem Cell Biology from the Faculty of Medicine at Lund University in 2010. She continued as a postdoc in Pasteur Institute of Iran and then started her second postoc at Karolinska Institutet. Phone: +46 (08)- 585 83623

Xiaoze Li, PhD, Postdoc.

She received her PhD in Virology and Microbiology from the Faculty of Medicine at Lund University in 2013. She started her postdoc at Karolinska Institutet in January 2014. Phone: +46(08)-58583623.

Ayla De Paepe, doctoral student.

She graduated as a Master of Science in Bioscience Engineering from Ghent University, Belgium. She started as a doctoral student at Karolinska Institutet in January 2014. Phone: +46 (0)7 - 627 734 31

Aleksandra Krstic, PhD, Postdoc.

She received her PhD in Molecular Medicine from the Faculty of Medicine at Belgrade University in 2012. She started her postdoc at Karolinska Institute in March 2013. Phone: +46(08)-58583623.

Projects

The hematopoietic system is maintained through the continuous generation of new mature effector cells from self-renewing multipotent progenitors. Development of mature cells occur gradually through series of hierarchically related developmental stages.

This gradual process coupled with the relative ease by which different developmental stages can be purified (based on stage and lineage specific surface markers) make hematopoiesis an ideal system for studying developmental progression. In particular the development of B-cells has been very well characterized leading to the identification of several successive stages of B-cell development. In addition a hierarchically organized network of transcription factors has been identified. This network includes several transcription factors (EBF1, E2A, PAX5, FOXO1 and others), all demonstrated to be critical for proper development and commitment to the B-cell lineage. Together this makes the development of B-cell possibly the most well understood developmental pathways to date.

However, even though the developmental pathway is well defined, our understanding of the molecular mechanisms that drive differentiation and lineage specification is still limited. Thus, a major challenge for the field is to understand how elaborate transcriptional programs drive these processes through temporal and cell-type specific gene expression.

Studies will explore the developmental progression from stem and progenitor cells into mature B-lymphoid cells and the transcriptional networks that drive this process.

More specifically, studies will be aimed at:

  1. Increasing our ability to resolve discrete stages of developmental progression.
  2. Using high resolution cell separation, coupled to genome wide approaches, to study changes in transcription factor usage with resulting effects on epigenetic marks and transcription in association with developmental progression.
  3. Identification and study of distal regulatory elements and how these interact with and modulate their transcriptional targets.

Financial support

  • Wallenberg Institute for Regenerative Medicine (WIRM)
  • Swedish Research Council (VR)

Selected publications

CCAAT/enhancer binding protein alpha (C/EBP(alpha))-induced transdifferentiation of pre-B cells into macrophages involves no overt retrodifferentiation.
Di Tullio A, Vu Manh T, Schubert A, Castellano G, Månsson R, Graf T
Proc. Natl. Acad. Sci. U.S.A. 2011 Oct;108(41):17016-21

The transcription factors E2A and HEB act in concert to induce the expression of FOXO1 in the common lymphoid progenitor.
Welinder E, Mansson R, Mercer E, Bryder D, Sigvardsson M, Murre C
Proc. Natl. Acad. Sci. U.S.A. 2011 Oct;108(42):17402-7

A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates B cell fate.
Lin Y, Jhunjhunwala S, Benner C, Heinz S, Welinder E, Mansson R, et al
Nat. Immunol. 2010 Jul;11(7):635-43

Single-cell analysis of the common lymphoid progenitor compartment reveals functional and molecular heterogeneity.
Mansson R, Zandi S, Welinder E, Tsapogas P, Sakaguchi N, Bryder D, et al
Blood 2010 Apr;115(13):2601-9

Hematopoietic stem cell expansion precedes the generation of committed myeloid leukemia-initiating cells in C/EBPalpha mutant AML.
Bereshchenko O, Mancini E, Moore S, Bilbao D, Månsson R, Luc S, et al
Cancer Cell 2009 Nov;16(5):390-400

EBF1 is essential for B-lineage priming and establishment of a transcription factor network in common lymphoid progenitors.
Zandi S, Mansson R, Tsapogas P, Zetterblad J, Bryder D, Sigvardsson M
J. Immunol. 2008 Sep;181(5):3364-72

E2A proteins promote development of lymphoid-primed multipotent progenitors.
Dias S, Månsson R, Gurbuxani S, Sigvardsson M, Kee B
Immunity 2008 Aug;29(2):217-27

B-lineage commitment prior to surface expression of B220 and CD19 on hematopoietic progenitor cells.
Mansson R, Zandi S, Anderson K, Martensson I, Jacobsen S, Bryder D, et al
Blood 2008 Aug;112(4):1048-55

Modeling of C/EBPalpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells.
Kirstetter P, Schuster M, Bereshchenko O, Moore S, Dvinge H, Kurz E, et al
Cancer Cell 2008 Apr;13(4):299-310

Elucidation of the phenotypic, functional, and molecular topography of a myeloerythroid progenitor cell hierarchy.
Pronk C, Rossi D, Månsson R, Attema J, Norddahl G, Chan C, et al
Cell Stem Cell 2007 Oct;1(4):428-42

The Cxcl12, periostin, and Ccl9 genes are direct targets for early B-cell factor in OP-9 stroma cells.
Lagergren A, Månsson R, Zetterblad J, Smith E, Basta B, Bryder D, et al
J. Biol. Chem. 2007 May;282(19):14454-62

The CD53 and CEACAM-1 genes are genetic targets for early B cell factor.
Månsson R, Lagergren A, Hansson F, Smith E, Sigvardsson M
Eur. J. Immunol. 2007 May;37(5):1365-76

Molecular evidence for hierarchical transcriptional lineage priming in fetal and adult stem cells and multipotent progenitors.
Månsson R, Hultquist A, Luc S, Yang L, Anderson K, Kharazi S, et al
Immunity 2007 Apr;26(4):407-19

Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential a revised road map for adult blood lineage commitment.
Adolfsson J, Månsson R, Buza-Vidas N, Hultquist A, Liuba K, Jensen C, et al
Cell 2005 Apr;121(2):295-306

Pearson correlation analysis of microarray data allows for the identification of genetic targets for early B-cell factor.
Månsson R, Tsapogas P, Akerlund M, Lagergren A, Gisler R, Sigvardsson M
J. Biol. Chem. 2004 Apr;279(17):17905-13

Open positions

We always want to get in touch with talented potential co-workers. If you are interested in doing research within our group, as a degree project or as a researcher, please contact the group leader Robert Månsson.

Links

HOMER - Software for motif discovery and next generation sequencing analysis

The fantastic next generation sequencing analysis package HOMER developed by Dr. Chris Benner at UCSD. Unfamiliar with sequencing analysis? Fear not, Chuck has been helping Chris make one of the few instruction manuals that you actually want to read!

HOMER

HematologyRegenerative Medicine