Autophagy and the hematopoietic niche
Two main components of the hematopoietic niche are hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). FOXO transcription factors play a fundamental role in the maintenance of these cells through the regulation of cell cycle and oxidative stress. Other gene expression programs controlled by FOXO include cell death, DNA repair and autophagy. Autophagy, has been found to be a general cellular housekeeping process critical for maintenance of quiescence, self-renewal and differentiation. The work described in Catalina Gomez-Puerto's thesis helps elucidate the functional importance of autophagy in human HSCs and MSCs and how this is regulated by FOXO. Importantly it provides insights as to how manipulation of autophagy and FOXO-activity could lead to novel therapeutic strategies targeting both bone marrow failure and leukemia. This work was funded by a grant from the Dutch Cancer Foundation (KWF).