The hematopoietic stem cell (HSC) is maintained in the adult bone marrow by complex networks of stromal cells as well as HSC progenies, which control HSC self-renewal and differentiation. The balanced production of all blood components is crucial for lifelong adaptation to infectious and environmental challenges and resilience of the entire organism. Skewing of hematopoiesis to myeloid lineages at the expense of lymphocytic differentiation is a hallmark of aging. This imbalance of blood cell production is considered a major contributor to age-related diseases ranging from cancer and cardiovascular failure to chronic inflammation and impaired adaptive immune responses. We identified a mutant mouse model with accelerated age-related myeloid skewing that persists in HSC transplanted into young mice. This observation allows us to generate large numbers of mice in which HSC prematurely age in otherwise young organisms. With these mice we have a unique mouse model of HSC-dependent immuno-aging to advance the central ReALity topic how system specific decline in aging and interventions targeting HSC influence other systems.
The investigators of this project will thoroughly characterize the bone marrow niche and hematopoietic cell composition of this mouse model and establish the response to different vaccination strategies as an initial proof of concept for defects in immuno-aging. The versatility of generating cohorts of mice with a prematurely aged hematopoietic system will allow us to provide mice, tissues and cells for functional and omics analysis to other investigators in ReALity.
Principal Investigators
- Prof. Dr. Wolfram Ruf, University Medical Center Mainz (contact person, e-mail)
- Dr. Borhane Guezguez, University Medical Center Mainz
- Dr. med. Sebastian Kreiter, TRON
- Dr. med. Michael Kühn, University Medical Center Mainz