Cell Instrinsic and Bone Marrow Niche Regulation of Stem Cell Rejuvenation
A finely regulated balance between quiescence and activation of the hematopoietic stem cells (HSC) ensures the continuous replenishment of all mature blood cells in homeostasis and on demand. Stem cell exhaustion is a hallmark of aging and results from combined effects of cell intrinsic and environmental deterioration. The resulting increase in myeloid output, called myeloid skewing, at the expense of the adaptive immune lymphocytes, has been associated with an increased risk for age-related cardiovascular diseases, immune-aging and myeloid premalignancies. The bone marrow (BM) microenvironment provides several environmental cues important for the maintenance of HSC. These originate from a variety of stromal cells which include mesenchymal stromal cells, megakaryocytes and endothelial cells. Dissecting cellular mechanisms and interactions of HSC with their environment holds great promise to develop therapies aimed at counteracting age-dependent stem cell exhaustion. These could ultimately lead to improved outcomes of age associated diseases.
This project builds on extensive available preliminary data, tissue banks, existing and new collaborations, and established methodologies to study aging in mice. The investigators will combine their expertise and dissect specific interactions between HSC and the BM microenvironment via the employment of recently identified murine models of premature aging of the hematopoietic system or of different cell population of the BM microenvironment.
Principle Investigators
Dr. Wolfram Ruf, Center for Thrombosis and Hemostasis (CTH),
University Medical Center (person of contact email)
Akilli Öztürk, IHC TRON gGmbH
Dr. Matthias Gaida, Institute of Pathology, University Medical Center
Borhane Guezguez, Department of Internal Medicine III, University Medical Center, German Cancer Research Center
Dr. Daniela Krause, Institute of Transfusion Medicine – Transfusionszentrale, University Medcial Center
Dr. Michael Kühn, Department of Internal Medicine III, University Medical Center
Valentina Rene Minciacchi, Center for Thrombosis and Hemostasis, University Medical Center
Dr. Stefan Tenzer, Institute of Immunology, University Medical Center
