Constructing a cell atlas of normal and diseased human heart

• Applicant: Dr. Christoph Sandmann
• Subject Area: Cardiology, Angiology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 559417649

Cardiovascular disease is a major cause of death in children. However, despite recent discoveries of numerous causes, mechanistic insights remain limited as there is no frame of reference for normal postnatal cardiac development. The morphological and functional changes that determine the transition from the neonatal to the mature adult human heart are mediated at the cellular level. However, the underlying cellular mechanisms of postnatal cardiac maturation in normal physiology and how these are affected in disease are incompletely understood in humans. Several of these changes that occur during cardiac maturation have been studied in animal models, primarily rodents. These studies revealed basic principles of cardiac development and showed how disruption of these complex mechanisms can lead to altered cardiac function and disease. However, while those previous studies of the underlying mechanisms of rodent heart development and maturation provide insight into these events they cannot suffice for human data. This project aims to establish a cell atlas of postnatal development and maturation of the human heart in the six regions left and right atrium, left and right ventricle, apex and interventricular septum. For this purpose, RNA sequencing of single nuclei will be applied to normal healthy and diseased human heart samples from male and female paediatric donors of different ancestry in three age groups (infants, toddlers, adolescents). The creation of an integrated atlas of paediatric human heart cells fills an important gap that is needed to gain deeper insights into human physiology and cardiac disease. The atlas will reveal how the postnatal human heart changes from birth to adulthood and how the maturation and development of specific cellular states allows the heart to adapt to postnatal conditions such as rapid perinatal changes, growth and pubertal influences. It will also clarify whether and how these processes change in diseased heart tissue in children with congenital heart defects.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Hosts: Professorin Christine Seidman, Ph.D.; Professor Jonathan G. Seidman, Ph.D.