Ludwig Institute for Cancer Research and Karolinska Institutet, Stockholm, Sweden
Thomas Perlmann defended his thesis at the Karolinska Institute and did a postdoc at the Salk Institute in San Diego with professor Ronald Evans. His work is focused on molecular mechanisms controlling the development of the central nervous system with a particular focus on how dopamine neurons are generated. Thomas Perlmann is currently a group leader at the Stockholm Branch of the Ludwig Institute and a professor at the department of Cell and Molecular Biology at the Karolinska Institute.
Stem cell engineering and grafting of mesencephalic dopamine (mesDA) neurons provides a promising strategy for brain repair in Parkinson’s disease. However, essential improvement of differentiation protocols will require deeper interrogation of mesDA neuron lineage development. In this seminar I will discuss our latest findings from studies using single-cell RNA sequencing of cells expressing the mesDA neuron transcription factor determinant Lmx1a. This approach resolved the differentiation of mesDA and neighboring neuronal lineages and revealed a remarkably close relationship between developing mesDA and subthalamic nucleus (STN) neurons. The combined ablation of Lmx1a and Lmx1b in mice disrupted both STN and mesDA neural development, while a distinct transcription factor set defined progenitors developing into STN neurons. Importantly, these and other bioinformatic approaches have resulted in improved human embryonic stem cell engineering into mesDA neurons for cell replacement therapy in Parkinson’s disease.
Host: Carl-Henrik Heldin
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