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Dynamic crosstalk between developing blood cells and mesenchymal stroma compartments
Linköping University, Department of Clinical and Experimental Medicine, Experimental Hematology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Experimental Hematology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Experimental Hematology. Linköping University, Faculty of Health Sciences.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

The development of hematopoietic cells in the bone marrow is dependent on cellular interactions between blood cell progenitors and mesenchymal stroma cells. In order to increase the understanding of how cells communicate in this specialized environment, we have developed software scripts that allow us to compare gene expression patterns in two cells types and extract information about potential interaction pathways. The gene expression data was generated from freshly isolated FACS purified BM cells of hematopoietic or mesenchymal origins. This proposed that defined mesenchymal populations provide specific components to the microenvironment. Furthermore, even though several communication pathways were shared by multiple hematopoietic developmental stages, stage specific interactions may be involved in the modulation of defined progenitor populations. Additionally the analysis suggested that there existed possibilities for the hematopoietic cells to signal to the stroma cells and for the stroma cells to signal to each other. Our analysis suggests existence of a highly complex and dynamic crosstalk in the BM microenvironment.

National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-72334OAI: oai:DiVA.org:liu-72334DiVA: diva2:459201
Available from: 2011-11-25 Created: 2011-11-25 Last updated: 2011-11-25Bibliographically 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)
Opponent
Supervisors
Available from: 2011-11-25 Created: 2011-11-25 Last updated: 2012-01-18Bibliographically approved

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Stjernberg, JennyQian, HongSigvardsson, Mikael

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