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Heparan sulfate SULFatases ensure correct patterning of stem cell–derived midbrain dopaminergic neurons

Midbrain dopaminergic (mDA) neuron loss underlies Parkinson’s disease (PD), making it critical to understand how mDA identity is established during development for cell replacement therapy. While intrinsic transcriptional programs and morphogen gradients driving mDA are known, the contribution of extracellular modulators remains less explored. Here, we show that the heparan sulfate (HS)–modifying enzymes SULF1 and SULF2 are essential for proper mDA neuron differentiation in vitro using CRISPR/Cas9-engineered human iPSCs, we demonstrate that SULF1/2 double knockout (DKO) cells.

Type: Transcriptome Sequencing
Archive: European Genome-phenome Archive (EGA)

1 Dataset

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Dataset ID	Description	Technology	Samples
EGAD50000001648	Single nuclei RNA-seq ( 10X Genomics Chromium Gem-X Single Cell 3' Kit v4) of 3 samples of hiPSC lines (cell line KOLF 2.1J iPSC). hiPSC cells were differentiated following a mDA neuron differentiation protocol in three samples: wild type (WT), SULF1/2 DKO and FGF-inhibited (PD/SU treated) SULF1/2 DKO. At day 16, nuclei were isolated from each sample and analyzed with snRNA-seq. Nuclei suspensions from each sample were loaded in different lanes. Reads annotated to chrY (hg38) were discarded from the fastq files following ethical agreements.	Illumina NovaSeq X	3