Investigating human neuronal transplantation integration and interaction at the single cell level

Projektbeschreibung

Erforschung der neuronalen Transplantation auf Einzelzellebene

Das Absterben von Nervenzellen trägt zum neuronalen Verlust bei, der bei chronischer Neurodegeneration und Demenzerkrankungen, wie der amyotrophen Lateralsklerose und Alzheimer, sowie teilweise auch bei zerebraler Ischämie und traumatischen Hirnverletzungen auftritt. Der Versuch, abgestorbene Neuronen per Transplantation zu ersetzen, ist aus medizinischer Perspektive vielversprechend und reizvoll. Doch damit daraus Realität wird, ist ein deutlich besseres Verständnis von der Integration der Transplantate und ihrer Interaktion mit der Wirtsumgebung nötig. Das im Rahmen der Marie-Skłodowska-Curie-Maßnahmen finanzierte Projekt NeurTransHet wird die Rolle einzelner Zellen, die Auswirkungen der Heterogenität von Transplantaten und die Interaktion der transplantierten Zellen mit der Umgebung an einem Mausmodell der menschlichen Neuronentransplantation ergründen. Diese Untersuchung wird mithilfe von Einzelzelltranskriptomik und hochauflösender Bildgebung an einem Mausmodell der menschlichen Neuronentransplantation durchgeführt.

Ziel

NeurTransHet will shed light on the heterogeneity of neuronal transplantations and the relationship with their environment. The aim of this project is to bring neuronal transplantation closer to clinical implementation by understanding the intricacies of individual transplanted cell contribution, and later applying this knowledge to engineer them. Neuronal loss underlies various brain disorders, such as Alzheimer’s disease, and injuries, such as traumatic brain injuries, resulting in life-long impairment. For example, dementia, a widespread (a new case every 3 seconds worldwide) condition stemming from neuronal loss, has devastating effects on the patients, their families and their communities. Thus, approaches aiming at replacing the lost neurons by transplantation are not only attractive from a health perspective, but also from a socio-economic standpoint. Many studies have explored neuronal transplantation, albeit with varying degrees of success. This is due to a lack in our understanding of how transplants integrate and interact with their host environment. Additionally, several studies gave evidence that transplanted cells are a heterogenous population, however, so far this heterogeneity has not been addressed in terms of function on integration and interaction. The recent advent of single cell transcriptomic technology, coupled with imaging techniques providing high-resolution spatial information, makes it possible to go beyond global interaction and closely dissect the individual neuronal transplants and their environment. Moreover, the possibility of transplanting cells of human origin in mice increases the clinical relevance of the results. During this two-year fellowship under the supervision of Prof. Dr. Magdalena Götz, who is a world-renowned scientist in neuronal cell replacement methodologies, I will transition into an independent research group leader investigating the role of cell heterogeneity in disease.