Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Chronic colitis induces a diverse neuroinflammatory fingerprint and myeloid cell-mediated dopaminergic neuron loss in the midbrain

ABSTRACT: Chronic gut inflammation is associated with neuroinflammation and brain diseases. Yet, the regional pattern and single-cell resolution of the brain immune response to chronic gut inflammation remains elusive. Combining confocal microscopy and multiomic analyses, we observed that chronic colitis-derived systemic inflammation results in a midbrain-specific inflammatory response characterized by an inflammatory shift of microglial clusters, CD8+ T cell extravasation, and increased numbers of vessel-associated neutrophil granulocytes. Myeloid cell targeting after colitis onset resulted in a 67% reduction of midbrain microglia and prevented dopaminergic neuron loss in the substantia nigra pars compacta. Collectively, we provide the first single-cell resolution of an innate and adaptive immune response to chronic gut inflammation in the midbrain and identified a detrimental role of myeloid cells in midbrain dopaminergic neuron loss. These results substantially advance the understanding of the gut-immune-brain axis that links peripheral inflammation to distinct neuroinflammatory and neurodegenerative processes related to Parkinson’s disease.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain, Colon

SUBMITTER: Pavel Kielkowski

LAB HEAD: Pavel Kielkowski

PROVIDER: PXD069675 | Pride | 2026-07-13

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	20240527_PK115_1.raw	Raw
	20240527_PK115_10.raw	Raw
	20240527_PK115_11.raw	Raw
	20240527_PK115_12.raw	Raw
	20240527_PK115_13.raw	Raw

Items per page:

1 - 5 of 22

Similar Datasets

Vimentin network dysregulation mediates neurite deficits in SNCA duplication Parkinson’s patient-derived midbrain neurons

Project description:Duplication of the SNCA gene (SNCADupl), linked to elevated levels of alpha-synuclein (aSyn), is a genetic cause of Parkinson's disease (PD). Our prior work with human-induced pluripotent stem cell (hiPSC)-derived midbrain neurons generated from PD SNCADupl patients identified neuritic deficits, accompanied by decreased levels of cytoskeletal element b-tubulin-III (bTubIII). To explore mechanisms underlying these effects in SNCADupl neurons, we employed CRISPR/Cas9 to generate isogenic control hiPSCs. Isogenic correction of SNCA dosage restored SNCADupl-induced neurite defects and bTubIII levels. Multi-omics analyses revealed SNCADupl-induced alterations in neuronal differentiation, with a notable downregulation of PAX6. Moreover, SNCADupl induced an upregulation of vimentin. Further characterization revealed heightened vimentin truncation, associated with altered distribution and organization. Similar changes in vimentin levels and truncation were observed in post-mortem putamen tissue from sporadic PD patients. Notably, targeting vimentin with okadaic acid and withaferin A restored bTubIII- and neurite-associated defects, suggesting its potential to prevent aSyn-mediated neuritic degeneration.

2025-07-16 | PXD063433 | Pride

Identification of USP39 Ligands and Their Application in Targeted Protein Degradation

Project description:Alternative splicing is a tightly regulated process essential for transcriptomic and proteomic diversity, and its dysregulation has been implicated in various cancers. Ubiquitin-specific protease 39 (USP39) is a core component of the spliceosome that lacks enzymatic activity, rendering it challenging to target with traditional small molecules. Here, we report the identification of small-molecule ligands that bind selectively to USP39 via a 2-aminothiazole scaffold, primarily interacting with its zinc finger domain. Structure–activity relationship studies guided the design of PROTACs (proteolysis-targeting chimeras), leading to the development of USP39_PROTAC_V1, which recruits the VHL E3 ligase. Biophysical and biochemical assays confirmed potent ternary complex formation and nanomolar binding affinities. In cellular models, USP39_PROTACs induced efficient degradation of USP39 at concentrations as low as 1 nM, with minimal off-target effects as shown by proteome-wide profiling. The degradation was abrogated by proteasome and neddylation inhibitors and was dependent on VHL-mediated recruitment. Importantly, PROTAC-induced USP39 depletion reproduced known splicing defects at 5’ splice sites, validating both the mechanism of action and the therapeutic relevance. Our study provides the demonstration of targeted USP39 degradation and highlights its potential as a tractable target in splicing-related pathologies.

2026-02-09 | PXD065738 | Pride

RNA-SEQ profiling of mouse whole midbrain and dopaminergic neurons from the mouse mid-brain

Project description:RNA-SEQ profiling of mouse whole midbrain and dopaminergic neurons from the mouse mid-brain Murine whole midbrain and murine midbrain dopaminergic neurons

2015-07-27 | E-GEOD-64526 | biostudies-arrayexpress

Bulk RNA-sequencing of defined brain regions of mice with chronic DSS-induced colitis and colitis induced bz intestinal epithelial-specific Opa1 deletion

Project description:Selected brain regions of mice with chronic DSS colitis and controls, and mice with colitis caused by induced, intestinal epithelial-specific Opa1 knock-out to study the impact of gut inflammation on the brain

2026-01-01 | E-MTAB-15488 | biostudies-arrayexpress

Heparan sulfate Sulfatases are essential for the patterning of human stem cell-derived midbrain dopaminergic neurons

Project 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.

2026-07-16 | PXD075443 | Pride

Proteomics of human iPSC derived dopaminergic neurons with a Parkinson's disease linked PARK7/DJ-1 mutation

Project description:Parkinson’s disease (PD) is characterized by α-synuclein accumulation and dopaminergic neuron degeneration, with dopamine (DA) oxidation emerging as a key pathological driver. However, the mechanisms underlying this neurotoxic process remain unclear. Using PD patient-derived and CRISPR-engineered iPSC midbrain dopaminergic neurons lacking DJ-1, we identified defective sequestration of cytosolic DA into synaptic vesicles, which culminated in DA oxidation and α-synuclein accumulation. In-depth proteomics, state-of-the-art imaging, and ultrasensitive DA probes uncovered that decreased VMAT2 protein and function impaired vesicular DA uptake, resulting in reduced vesicle availability and abnormal vesicle morphology.

2026-01-07 | PXD069663 | Pride

Dysregulation of the colonic mucosally-adherent microbiota associates with HIV disease progression.

Project description:HIV is known to severely affect the gastrointestinal immune system, in particular compartments of immunity that regulate gut microbial composition. Furthermore, recent studies in mice have shown that dysregulation of the gut microbiome can contribute to chronic inflammation, which is a hallmark of HIV and is thought to fuel disease progression. We sought to understand whether the gut microbial community differs in HIV-infected subjects, and whether such putative differences are associated with disease progression. We found that dysbiosis in the gut mucosally-adherent bacterial community associates with markers of chronic inflammation and disease progression in HIV-infected subjects, and this dysbiosis remains in many subjects undergiong antiretroviral therapy. We used G3 PhyloChip microarrays (commercially available from Second Genome, Inc.) to profile gut bacteria in rectosigmoid biopsies from 32 subjects: 6 HIV-infected viremic untreated (VU), 18 HIV-infected subjects on highly active antiretroviral therapy (HAART), 1 HIV-infected long-term non-progressor that is untreated (LTNP), and 9 HIV-uninfected subjects (HIV-).

2013-07-10 | E-GEOD-43746 | biostudies-arrayexpress

Gene expression analysis of midbrain dopamine progenitors in embryonic mouse

Project description:To improve the standardization of cell therapies for Parkinson’s disease, methods for the selection and isolation of midbrain dopaminergic progenitors for transplantation are required. To facilitate this we established an expression profile for genes selectively expressed on transplantable midbrain dopaminergic progenitors using microarray analysis. Expression of GFP in the ventral mesencephalon of embryonic E12.5 Ngn2-GFP mice identifies a distinct sub-population of cells containing virtually all of the midbrain dopaminergic progenitors. Gene expression profiles from 3 biological replicates of FACS isolated GFP-positive cells from mouse Ngn2-GFP ventral mesencephalon were generated using microarrays. To reduce the likelihood of identifying transcripts from non-dopaminergic progenitors, 3 biological replicates of FACS isolated GFP-negative cells from mouse Lmx1a-GFP ventral mesencephalon (definitively non-dopaminergic) were used as a reference population.

2015-02-28 | E-GEOD-65094 | biostudies-arrayexpress

Caspase inhibition restores dopaminergic identity through the PKA–CREB–BDNF axis in Parkinson’s disease neurons

Project description:The progressive loss of dopaminergic identity in midbrain neurons is a hallmark of Parkinson’s disease (PD), contributing to synaptic dysfunction and neurodegeneration. However, the molecular mechanisms linking disease-specific stress to dopaminergic transcriptional failure remain poorly understood. Here, we used human induced pluripotent stem cell (hiPSC)-derived midbrain dopaminergic neurons (mDAs) from sporadic PD patients to investigate early alterations in neuronal identity, plasticity, and survival. We found that PD-derived mDAs exhibit upregulation of phosphorylated α-synuclein, marked reductions in dopaminergic markers (TH, NURR1), deficient dopamine handling and impaired synaptogenesis. Transcriptomic and protein analyses revealed sustained activation of apoptotic caspases (caspase-3, -7) and downregulation of the PKA–CREB–BDNF signaling axis, which underpins dopaminergic differentiation and synaptic maturation. Pharmacological inhibition of caspases with Q-VD-OPh restored pCREB, BDNF, and downstream dopaminergic markers, leading to morphological recovery and functional synaptic rescue. Inhibition of PKA with H89 abrogated these effects, positioning the caspase–PKA–CREB cascade as a critical regulator of dopaminergic identity in PD neurons. These findings define a novel non-apoptotic role for caspases in disrupting the transcriptional program of mDAs and identify a druggable pathway capable of rescuing key aspects of dopaminergic function in a patient-derived cellular model. This work provides a mechanistic rationale for targeting caspase signaling in early-stage PD.

2026-06-08 | PXD066765 | Pride

ChIP-seq analysis of Foxa2 binding sites in midbrain dopaminergic progenitors

Project description:Embryonic stem (ES) cells were differentiated in culture to midbrain dopaminergic (mDA) progenitors and subjected to ChIP-seq analysis to resolve genome-wide binding sites of forkhead box protein A2 (Foxa2). Foxa2 was found to directly regulate multiple lineage pathways to specify midbrain dopaminergic and floor plate progenitor identity.

2012-07-01 | E-MTAB-1137 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data