A protocol for the differentiation of human embryonic stem cells into midbrain dopaminergic neurons

Nishimura, Kaneyasu; Ásgrímsdóttir, Emilía Sif; Yang, Shanzheng; Arenas, Ernest

doi:10.1016/j.xpro.2023.102355

Cited by 5 publications

(1 citation statement)

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“…S7A) and then selected a few molecules from the Wnt, Bmp, and angiotensin II (AngII) pathways to investigate in human embryonic stem cells (hESCs) (Table 2). A human development-based protocol (Nishimura et al, 2023a) was used to differentiate WA09 cells into cells of the mDA lineage that are comparable to their endogenous counterparts, as assessed by scRNA-seq (Nishimura et al, 2023b). Ligands or small molecules were added to the cultures between days 22 and 35 of differentiation (Fig.…”

Section: Resultsmentioning

confidence: 99%

Midbrain Dopaminergic Neuron Development is Regulated by Two Molecularly Distinct Subtypes of Radial Glia Cells

Ásgrímsdóttir,

Bassini,

di Val Cervo

et al. 2024

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Understanding midbrain dopaminergic (mDA) neuron development is key to advancing cell replacement therapies for Parkinson's disease (PD). Recent single-cell RNA-sequencing (scRNA-seq) studies have identified different subtypes of transient radial glia (Rgl) cell types in the developing mouse and human ventral midbrain. However, their individual functions and their impact on mDA neuron development are unclear. Here we analyze the transcriptome of endogenous mouse and human ventral midbrain Rgl and assess the function of key midbrain floor plate Rgl factors in human stem cells during mDA neuron differentiation. We find that Rgl1 is defined by a neurogenic network centered on Arntl, and that this transcription factor regulates human mDA neurogenesis. Conversely, the transcriptome of Rgl3 is dominated by signaling and extracellular matrix molecules that control different aspects of human mDA neuron development. Thus, our results suggest a function of Rgl1 as a mDA progenitor, and of Rgl3 as a signaling mDA niche cell. Moreover, using human stem cells we demonstrate that new knowledge of cell-type specific intrinsic and extrinsic developmental factors can readily be applied to improve the generation of cells with therapeutic interest, such as human mDA neurons for PD.

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Section: Resultsmentioning

confidence: 99%