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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Uppsala universitet, Historiska institutionen
  • Ludwig Institute for Cancer Research, Uppsala branch
  • Karolinska Institute
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cell- och molekylärbiologi
  • Cancer och onkologi

Nyckelord

Originalspråkengelska
Sidor (från-till)29-40
Antal sidor12
TidskriftCell Stem Cell
Volym20
Utgivningsnummer1
StatusPublished - 2017 jan 5
PublikationskategoriForskning
Peer review utfördJa