PXD075443-1

PXD075443 is an original dataset announced via ProteomeXchange.

Title	Heparan sulfate Sulfatases are essential for the patterning of human stem cell-derived midbrain dopaminergic neurons
Description	Midbrain dopaminergic neurons (mDA) are selectively lost in Parkinson’s disease (PD), driving sustained efforts to generate bona fide mDA neurons from human-induced pluripotent stem cells (iPSCs) for replacement therapy. While morphogen gradients and transcription factors have been extensively studied, extracellular regulators remain largely overlooked. Here, we identify the heparan sulfate-modifying enzymes SULF1 and SULF2 as essential for establishing mDA neuron identity in vitro. Using CRISPR/Cas9-engineered iPSCs, we show that loss of SULF1/2 increases 6-O-sulfation of heparan sulfate chains and disrupts anterior-posterior and dorsoventral patterning in cells exposed to a midbrain differentiation protocol. Double-knockout cells fail to acquire midbrain fate and instead adopt caudal and neural crest-like identities, as revealed by single-nucleus RNA sequencing. Mechanistically, we find enhanced FGF signaling and demonstrate that FGF inhibition redirects cells toward midbrain progenitors, without fully restoring ventral identity. These findings establish a critical role for SULF1/2 in human mDA neuron development and uncover a previously unrecognized layer of extracellular control over neuronal patterning, opening for novel strategies to refine differentiation protocols for PD and beyond.
HostingRepository	PRIDE
AnnounceDate	2026-07-16
AnnouncementXML	Submission_2026-07-16_05:03:47.987.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Luke Gamon
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-10 06:44:46	ID requested
⏵ 1	2026-07-16 05:03:48	announced

Dataset with its publication pending

submitter keyword: Human, iPSC

Michael Davies
contact affiliation	Department of Biomedical Sciences, University of Copenhagen, Denmark
contact email	davies@sund.ku.dk
lab head
Luke Gamon
contact affiliation	The University of Copenhagen
contact email	lgamon@sund.ku.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD075443
     1. Label: PRIDE project
     2. Name: Heparan sulfate Sulfatases are essential for the patterning of human stem cell-derived midbrain dopaminergic neurons