PXD045073-1

PXD045073 is an original dataset announced via ProteomeXchange.

Title	Multi-omic analyses of hiPSC-derived astrocytes during differentiation
Description	Astrocytes are essential players in brain development and functions, being particularly relevant as regulators of energy metabolism, ionic homeostasis, and synaptic transmission. They are also the major source of L-serine (L-Ser) in the brain, which is synthesized from the glycolytic intermediate 3-phosphoglycerate through the phosphorylated pathway (PP), which comprises 3- phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase (PSAT) and phosphoserine phosphatase (PSP). L-Ser is the precursor of the two main co-agonists of the N-methyl-D-aspartate receptors, glycine and D-serine. Remarkably, astrocytes also contribute to neurodegenerative disorders by various mechanisms, including metabolic alterations. We generated human mature astrocytes from pluripotent stem cells (hiPSC) to get a picture of the changes that occur during astrocytes differentiation and here we report the metabolic rewiring occurring during differentiation. We have recently reported that the levels of the enzymes of the PP are increased in Alzheimer’s disease brains. Following this observation, we overexpressed PHGDH, PSAT or PSP in the hiPSC-derived astrocyte model and significant metabolic alterations were apparent. These results provide a valuable model for developing potential novel approaches to address brain diseases, especially those related to serine metabolism alterations. By exploiting the potential of hiPSCs, we studied the cellular processes timely involved in the differentiation program. The molecular understanding of astrocyte differentiation from NSCs is an important aspect to consider for modulating astrocyte physiology in human pathologies and for developing potential therapeutic strategies. By overexpressing the enzymes of the PP pathway, we demonstrated that this model is a valuable tool for developing potential novel approaches to address brain diseases, especially those related to serine metabolism alterations.
HostingRepository	PRIDE
AnnounceDate	2025-08-25
AnnouncementXML	Submission_2025-08-24_16:29:34.452.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Simona Nonnis
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-04 02:12:04	ID requested
⏵ 1	2025-08-24 16:29:35	announced

Tripodi F, Maffioli E, Sacchi S, Rabattoni V, Motta Z, Bearzi C, Tedeschi G, Pollegioni L, Coccetti P, Modulating the serine metabolism in human differentiated astrocytes: an integrated multi omics approach. Front Cell Neurosci, 19():1616911(2025) [pubmed]

10.3389/fncel.2025.1616911;

submitter keyword: proteomics;nanoLC-MS/MS

Elisa Maffioli
contact affiliation	DIVAS, University of Milan
contact email	elisa.maffioli@unimi.it
lab head
Simona Nonnis
contact affiliation	University of Milan
contact email	simona.nonnis@unimi.it
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD045073
     1. Label: PRIDE project
     2. Name: Multi-omic analyses of hiPSC-derived astrocytes during differentiation