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A step forward in cell reprogramming


Dj, 05/11/2009 - 18:00

A step forward in cell reprogramming


Investigators from the Centre for Genomic Regulation (CRG) describe a reprogramming system through which B lymphocytes are converted into macrophages in 2 to 3 days.
The work which is published in the prestigious journal Cell Stem Cell also features on the cover and presents the results of the research group led by Thomas Graf.

There are increasingly more research groups that try to discover the mechanisms of cell differentiation in order to reprogramme differentiated cells. On this occasion, investigators from the CRG have described a process of cell reprogramming which results in morphologically and functionally distinct cells with a 100% efficiency rate.
Specifically, the researchers have used B lymphocyte precursor cells and reprogrammed them in order to transform them into macrophages using the inducible expression of only one transcription factor. Both types of cells form part of the immune system but are morphologically, structurally and functionally very different. Whereas type B lymphocytes are antibody-producing cells, macrophages are responsible, via phagocytosis, for the elimination of both foreign agents introduced into the body and dead tissue cells.
In this way, the new macrophages induced by the system described by the investigators are bigger than the original cells, they contain different cellular organelles and the structure of their cytoskeleton is modified, so they have phagocytic capacity and respond to inflammation stimuli. Moreover, it was observed that the cells acquire their new form and function a few hours after induction. Two or three days later these lymphocytes have converted into completely autonomous macrophages.
“The speed and efficiency of the reprogramming has not been achieved in any other type of cell. For example, in studies of the famous reprogramming of somatic cells to iPS cells (or embryonic stem cells) there always exists a high percentage of the cellular population that is not reprogrammed. This makes the study of the reprogramming mechanism at a molecular level very difficult. For this reason, the new system described is a unique tool for the study of biochemical and biological aspects of cell reprogramming” asserts Thomas Graf, coordinator of the Cell Differentiation and Cancer programme of the Centre for Genomic Regulation and principal investigator in this work.
This study forms part of the cell reprogramming project of the CRG, a project in which all of the research programmes of the centre collaborate. The ultimate goal of this project is to understand the differentiation of the cells in various tissues of the body, a fundamental process in all multicellular organisms and which we still understand very little of. In the future these studies will enable us to generate differentiated cells “a la carte” from cultured cell biopsies. In this way not only will immunologic rejection be avoided, but the application of this in regenerative medicine would also be much simpler and perhaps less dangerous than the use of embryonic stem cells (iPS or ES).
About Thomas Graf:
Thomas Graf is of Austrian-German origin and was raised in Venezuela. 
Since October 2006 he is the Coordinator of the Differentiation and Cancer Programme at the Center for Genomic Regulation in Barcelona, Spain. Before that he was a a Group Leader at the Max Planck Institute in Tuebingen, German Cancer Research Center in Heidelberg, a Programme Coordinator at the European Molecular Laboratory in Heidelberg, and Professor at Albert Einstein College of Medicine in New York.
In his early work he showed that at least two viral oncogenes are needed to cause leukemia in an avian model. He also demonstrated that a differentiation block is an essential feature in leukemogenesis. More recently he showed that specific transcription factors can efficiently reprogram specialized blood cells into another. He is now studying the molecular processes by which already specified cells can be reprogrammed to acquire new fates. These studies might help in efforts to generate desired cell types with an application in regenerative medicine.
Dr. Graf has received the Paul Ehrlich Prize, among several others. He has organized conferences on oncogenes, growth control, hematopoiesis, leukemia and stem cells and serves as editor on a number of journals, including Cell Stem Cell. He is a member of EMBO , Academia Europaea and the board of directors of the International Society for Stem Cell Research (ISSCR).
Reference work: Bussman et al. (2009) “A Robust and Highly Efficient Immune Cell Reprogramming System”. Cell Stem Cell.(2009)  doi: 10.1016/j.stem.2009.10.004
For further information: Laia Cendrós, Dept. Comunicació i RRPP, Centre de Regulació Genòmica (CRG), Dr. Aiguader, 88 – Edif. PRBB, 08003 Barcelona. Tel. +34 93 316 02 37.