Paris, July 23, 2009
Stem cells are a source of much hope, thanks to their extraordinary ability to produce all types of cell in the body or an organ, depending on their origin. Scientists are now trying to understand the mechanisms that commit stem cells to a particular specialization.
At the Centre d'Immunologie de Marseille-Luminy, CNRS
and INSERM researchers have been working on mouse hematopoietic stem cells. They studied the development of myeloid
cells, a lineage of white blood cells that combats microorganisms by
"eating" them, by releasing toxins or by alerting other specialized
immune cells. Until now, it was thought
that the production of different specialized cells from a hematopoietic stem
cell was a random process. Sieweke's
team has discovered that in the case of myeloid cells, it is the combined
action of two proteins which is relevant; one protein that is situated inside
the cell (transcription factor) and the other outside (a cytokine).
Transcription factors are capable of switching genes
on or off. The identity of a cell is the
combination of active genes it possesses.
Because of this, scientists already suspected that transcription factors
played an important role in the orientation of differentiation. They also knew that blood cells can only
prosper in an environment containing a particular cytokine, a type of hormone
specific to each cell type. But until
now, they thought that cytokines assisted the survival and renewal of cells
without affecting their "fate".
The team in Marseille has now shown that a specific cytokine (M-CSF)
places stem cells on a "myeloid pathway", but that these stem cells
can only follow this path if levels of a certain transcription factor (MafB)
within the cells is low. These findings
help to solve a mystery that has fascinated specialists during the past fifty
years. In the longer term, these results
may throw new light on the mechanisms of leukemia, where abnormal stem cells
remain "undecided" and are still able to escape therapy.
now, studies on hematopoietic stem cells had opened the way to research on stem
cells in other tissues. In this context,
the results achieved and published by Michael Sieweke and his colleagues may provide
more general information on how stem cells function (in the brain, muscle or
© Frédéric Mourcin Microscopy image of a hematopoietic stem cell (in yellow) surrounded by other cells, in a spleen section.
© Frédéric Mourcin
Microscopy image of a hematopoietic stem cell (in yellow) surrounded by other cells, in a spleen section.
Université Aix Marseille 2/CNRS/INSERM
MAFB Restricts M-CSF Dependent Myeloid Commitment Divisions of Hematopoietic Stem Cells,
Sandrine Sarrazin, Noushine Mossadegh-Keller, Taro Fukao, Athar Aziz, Frederic Mourcin, Laurent Vanhille, Louise M. Kelly-Modis, Philippe Kastner, Susan Chan, Estelle Duprez, Claas Otto and Michael H. Sieweke, Cell, 24 July 2009 .
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