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Cell Biology

Stem Cells : Renewal vs Differentiation

Hematopoietic stem cells (HSC) can potentially give rise to any of the blood cell types. But when a stem cell divides, how is the decision taken to simply duplicate itself or to differentiate into a specific new cell type?
A team led by Michael Sieweke at the Immunology Center of Marseille-Luminy1 addressed this question by examining how hematopoietic stem cells generate myeloid cells, a type of white blood cell that fights infections. To gather evidence, lab member Sandrine Sarrazin investigated the very first divisions of stem cells drawn from mouse bone marrow.2
“To isolate stem cells, we harvested all the cells contained in the bone marrow, then sorted hematopoietic stem cells by Fluorescence Activated Cell Sorting (FACS),” she explains. These cells were then either studied in vitro or reinjected into the spleen of a mouse, to follow their commitment to the myeloid lineage in situ.”
The team discovered that the decision to generate myeloid cells results from the joint action of two proteins. One is located inside the cell (a transcription factor, which turns different genes on or off), while the other is a cytokine—a small protein that carries signals locally between cells and stimulates them to proliferate. “We have shown that the transcription factor MafB modulates stem cells' sensitivity to the cytokine M-CSF,” explains Sieweke. When MafB level is high, stem cells are less sensitive to the action of M-CSF. Conversely, reduced levels of MafB make it possible for the cytokine to stimulate the stem cell to specifically give rise to myeloid cells.
Although focused on hematopoietic stem cells, this study might be relevant for other types of stem cells. It may also provide clues on how abnormal blood stem cells multiply in leukemia, and help develop treatment methods. Potentially, one might also learn how to orient the differentiation of blood cells in a deliberate direction, for example making more white blood cells to fight an infection.

Melisande Middleton

Notes :

1. Université Aix-Marseille-II / CNRS / Inserm.
2. S. Sarrazin et al., “MafB Restricts M-CSF-Dependent Myeloid Commitment Divisions of Hematopoietic Stem Cells,” Cell, 2009. 138: 300-13.

Contacts :

Michael Sieweke,
CNRS, Marseille.


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