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The Cxcl12, Periostin, and Ccl9 genes are direct targets for early B-cell factor in OP-9 stroma cells
Department for Hematopoetic Stem Cell Biology, Lund Stemcell Center, Lund University, Lund, Sweden.
Department for Hematopoetic Stem Cell Biology, Lund Stemcell Center, Lund University, Lund, Sweden.
Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Linköping University, Faculty of Health Sciences.
Department for Hematopoetic Stem Cell Biology, Lund Stemcell Center, Lund University, Lund, Sweden.
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2007 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 282, no 19, 14454-14462 p.Article in journal (Refereed) Published
Abstract [en]

The development of blood cells from hematopoietic stem cells in the bone marrow is dependent on communication with bone marrow stroma cells, making these cells central for the appropriate regulation of hematopoiesis. To identify transcription factors that may play a role in gene regulation in stroma cells, we performed comparative gene expression analysis of fibroblastic NIH3T3 cells, unable to support hematopoiesis in vitro, and OP-9 stroma cells, highly efficient in this regard. These experiments revealed that transcription factors of the early B cell factor (EBF) family were highly expressed in OP-9 cells as compared with the NIH3T3 cells. To identify potential targets genes for EBF proteins in stroma cells, we overexpressed EBF in fibroblasts and analyzed the pattern of induced genes by microarray analysis. This revealed that EBF was able to up-regulate expression of among others the Cxcl12, Ccl9, and Periostin genes. The identification of relevant promoters revealed that they all contained functional EBF binding sites able to interact with EBF in OP-9 cells. Furthermore, ectopic expression of a dominant negative EBF protein or antisense EBF-1 RNA in OP-9 stroma cells resulted in reduced expression of these target genes. These data suggest that EBF proteins might have dual roles in hematopoiesis acting both as intrinsic regulators of B-lymphopoiesis and as regulators of genes in bone marrow stroma cells. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc.

Place, publisher, year, edition, pages
2007. Vol. 282, no 19, 14454-14462 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-39974DOI: 10.1074/jbc.M610263200Local ID: 51893OAI: oai:DiVA.org:liu-39974DiVA: diva2:260823
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Knock Knock Knock, Who is there? - Cell Crosstalk within the Bone Marrow
Open this publication in new window or tab >>Knock Knock Knock, Who is there? - Cell Crosstalk within the Bone Marrow
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis is focused on the subject of cell-cell interaction. Our body is composed of cells, most of them are integrated in a network with other cells that together forms tissues and organs. Every cell type in these complex organs has its special task and location. This is true whether we are doing research on humans or, as we have been, investigating mice. Mice are excellent models for studies of blood cell development since this process in mice resembles human blood cell generation in many regards.

Cells communicate with each other by sending out small molecules or by directly binding to surrounding cells; to cells of the same kind as well as to cells with different origins and tasks. A cell is surrounded by hundreds of different signal-carrying entities; soluble, bound to the extra cellular matrix or bound to its surface. Every cell has to distinguish and respond to the environment according to its own specific nature.

In the first article interleukin 7 (IL-7) a growth factor expressed by the stroma cells was studied. Results show that IL-7 is crucial for the immature progenitor cell in its development towards antibody producing B-lymphocytes. The second article is about stroma cells and their ability to support the development of B-cells. It is a comparative study on two different cell lines, where we focus on transcription factors and their regulation of protein induction of factors supporting B-cells. This study increased our knowledge of stroma cells. In the third paper we combined our knowledge from the first two papers in regard to stroma cells as well as B-cell development by testing if there is a possibility to theoretically find new factors of importance for the maturing B-cell. We achieved this by the development of GCINT, a database investigating possible receptorligand interactions between two cells, verifying these results in vitro with cell lines as well as primary cells. This revealed a two way communication between blood cells and stroma cells, highlighting the complexity of the bone marrow environment. In the last article we continued this work with primary FACS sorted stroma cells investing the potential connections between each of the stroma cell populations with primary blood cells in different stages of development. This work supports a model where hematopoietic cells can interact with stroma cells in a stage-specific manner and that the exchange between cells is of importance for their maturation.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2011. 70 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1280
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-72336 (URN)978‐91‐7393‐016‐1 (ISBN)
Public defence
2011-12-15, Eken, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 09:00 (English)
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Available from: 2011-11-25 Created: 2011-11-25 Last updated: 2012-01-18Bibliographically approved

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Zetterblad, JennySigvardsson, Mikael

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