A Step Forward In Cell Reprogramming

Main Category: Stem Cell Research
Article Date: 07 Nov 2009 - 1:00 PST

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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).

Source: Centre for Genomic Regulation