Cellular and Molecular Basis of de novo Thymus Regeneration

• Applicant: Dr. Maximina Yun
• Subject Area: Developmental Biology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 450807335

Although regenerative abilities are generally restricted among vertebrates, salamanders such as axolotls (Ambystoma mexicanum) are exceptional in their capacity to regenerate entire limbs as well as large parts of various structures including brain, eye, spinal cord and heart. We have recently found that, surprisingly, the axolotl can regenerate an entire organ, the thymus, de novo (Yun lab, unpublished). The thymus is a central organ of the adaptive immune system that plays a crucial role in T-cell development and specialisation, essential for the establishment of self-tolerance and mounting of responses against external pathogens such as viruses. In humans, the thymus starts a degeneration process following puberty which is associated with impaired immune responses, poor recovery after immune-suppression, and age-related afflictions. Thus, understanding how the thymus can be fully regenerated, as the axolotl does, is relevant to therapeutic efforts to promote thymus regeneration or replacement to combat pathological and age-related declines in immune function. To our knowledge, the axolotl is the only organism able to regenerate its thymus de novo, yet nothing is known about this process. Hereby we propose to characterise axolotl thymus regeneration at single-cell resolution, determine how this fascinating process is regulated at the molecular level, and establish the identity of the cells which give rise to the new thymus. This study will generate basic and translational insights of relevance to the fields of stem cells, development, immunology and aging.

• DFG Programme: Research Grants