Single-Cell Analysis Reveals a Close Relationship between Differentiating Dopamine and Subthalamic Nucleus Neuronal Lineages

Research output: Contribution to journalArticle

Abstract

Stem cell engineering and grafting of mesencephalic dopamine (mesDA) neurons is a promising strategy for brain repair in Parkinson's disease (PD). Refinement of differentiation protocols to optimize this approach will require deeper understanding of mesDA neuron development. Here, we studied this process using transcriptome-wide single-cell RNA sequencing of mouse neural progenitors expressing the mesDA neuron 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, while also highlighting a distinct transcription factor set that can distinguish between them. While previous hESC mesDA differentiation protocols have relied on markers that are shared between the two lineages, we found that application of these highlighted markers can help to refine current stem cell engineering protocols, increasing the proportion of appropriately patterned mesDA progenitors. Our results, therefore, have important implications for cell replacement therapy in PD.

Details

Authors
Organisations
External organisations
  • Uppsala University
  • Ludwig Institute for Cancer Research, Uppsala branch
  • Karolinska Institutet
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
  • Cancer and Oncology

Keywords

  • development, dopamine, embryogenesis, graph clustering, hypothalamus, neurogenesis, Parkinson's disease, single cell RNA-seq, stem cell, subthalamic nucleus
Original languageEnglish
Pages (from-to)29-40
Number of pages12
JournalCell Stem Cell
Volume20
Issue number1
Publication statusPublished - 2017 Jan 5
Publication categoryResearch
Peer-reviewedYes