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Engrailed-1 Potentiates Mitochondrial Transplant Neuroprotection in Spinal Cord Ischemia-Reperfusion Injury [RNA-Seq]

ABSTRACT: Spinal cord ischemia-reperfusion injury (SCI/RI) is characterized by severe mitochondrial dysfunction and neuronal apoptosis. The transcription factor Engrailed-1 (En-1) has been identified as a potential regulator of mitochondrial homeostasis and neuroprotection. In this study, we utilized an integrated multi-omics approach to elucidate the molecular mechanisms by which En-1 protects cells from ischemia-like injury. We performed RNA-sequencing (RNA-seq) on PC12 cells with stable En-1 overexpression and their respective controls under both normoxic and oxygen-glucose deprivation/reoxygenation (OGD/R) conditions. To identify direct genomic targets of En-1, Cleavage Under Targets and Tagmentation (CUT&Tag) analysis was conducted. Integration of transcriptomic and DNA-binding profiles revealed a distinct regulatory network through which En-1 modulates mitochondrial function and cell survival. These data provide a comprehensive resource for understanding the transcriptional landscape governed by En-1 and identify potential therapeutic targets for mitigating mitochondrial damage in ischemic neural injuries.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE322512 | GEO | 2026/04/17

REPOSITORIES: GEO

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Engrailed-1 Potentiates Mitochondrial Transplant Neuroprotection in Spinal Cord Ischemia-Reperfusion Injury

Project description:Spinal cord ischemia-reperfusion injury (SCI/RI) is characterized by severe mitochondrial dysfunction and neuronal apoptosis. The transcription factor Engrailed-1 (En-1) has been identified as a potential regulator of mitochondrial homeostasis and neuroprotection. In this study, we utilized an integrated multi-omics approach to elucidate the molecular mechanisms by which En-1 protects cells from ischemia-like injury. We performed RNA-sequencing (RNA-seq) on PC12 cells with stable En-1 overexpression and their respective controls under both normoxic and oxygen-glucose deprivation/reoxygenation (OGD/R) conditions. To identify direct genomic targets of En-1, Cleavage Under Targets and Tagmentation (CUT&Tag) analysis was conducted. Integration of transcriptomic and DNA-binding profiles revealed a distinct regulatory network through which En-1 modulates mitochondrial function and cell survival. These data provide a comprehensive resource for understanding the transcriptional landscape governed by En-1 and identify potential therapeutic targets for mitigating mitochondrial damage in ischemic neural injuries.

2026-04-17 | GSE322513 | GEO

Engrailed-1 Potentiates Mitochondrial Transplant Neuroprotection in Spinal Cord Ischemia-Reperfusion Injury [OE]

2026-04-17 | GSE322514 | GEO

Engrailed-1 Potentiates Mitochondrial Transplant Neuroprotection in Spinal Cord Ischemia-Reperfusion Injury

Project description:Engrailed-1 Potentiates Mitochondrial Transplant Neuroprotection in Spinal Cord Ischemia-Reperfusion Injury

| PRJNA1430255 | ENA

Engrailed-1 Potentiates Mitochondrial Transplant Neuroprotection in Spinal Cord Ischemia-Reperfusion Injury [OE]

Project description:Engrailed-1 Potentiates Mitochondrial Transplant Neuroprotection in Spinal Cord Ischemia-Reperfusion Injury [OE]

| PRJNA1430246 | ENA

Engrailed-1 Potentiates Mitochondrial Transplant Neuroprotection in Spinal Cord Ischemia-Reperfusion Injury [RNA-Seq]

Project description:Engrailed-1 Potentiates Mitochondrial Transplant Neuroprotection in Spinal Cord Ischemia-Reperfusion Injury [RNA-Seq]

| PRJNA1430248 | ENA

Time resolved ribosome profiling study of oxygen and glucose deprivation of rat pheochromocytoma cells

Project description:Oxygen and glucose metabolism plays a pivotal role in many (patho)physiological conditions. In particular, oxygen and glucose deprivation (OGD) occurs during ischemia and stroke, resulting in extensive tissue injury and cell death. We applied time-resolved ribosome profiling technique to assess early events at the level of gene expression in rat pheochromocytoma PC12 cells during short-term OGD. Most substantial alterations in transcripts levels and their translation were seen to occur in the first 20 minutes of OGD. The rapid adaptation of translation apparatus to OGD is global and involves altered elongation and initiation rates. We also observed salient and reproducible alterations in ribosome densities of individual mRNAs such as increased translation of particular upstream Open Reading Frames (uORFs); induced site-specific arrests of the ribosomes and synthesis of extended protein isoforms. Ribosome profiling (with mRNA-seq sequencing) was carried out at 0,20,40 and 60 minutes of OGD. Two biological replicates were used.

2015-04-10 | E-GEOD-60752 | biostudies-arrayexpress

Time resolved ribosome profiling study of oxygen and glucose deprivation of rat pheochromocytoma cells

2015-04-10 | GSE60752 | GEO

Identification of Blood-Brain Barrier Injury-Related Biomarkers in Cerebral Infarction Using Transcriptomic Analysis

Project description:Background: Cerebral infarction leads to blood-brain barrier (BBB) disruption, exacerbating brain injury through edema, inflammation, and neuronal death. Although BBB damage is a critical event in stroke pathology, the underlying molecular mechanisms and reliable biomarkers remain poorly understood. This study aimed to identify key biomarkers associated with BBB injury following cerebral infarction using an in vitro model and transcriptomic approaches. Human cerebral microvascular endothelial cells (hCMEC/D3) were subjected to oxygen-glucose deprivation (OGD) and OGD/reoxygenation (OGD/R) to simulate ischemic and reperfusion injury. Cell viability, inflammatory cytokines, LDH release, and angiogenesis were assessed. Transcriptomic sequencing, weighted gene co-expression network analysis (WGCNA), and random forest algorithms were employed to identify differentially expressed genes and key biomarkers. OGD treatment significantly increased IL-1β, IL-6, TNF-α, and LDH levels, which were partially reversed by OGD/R. Transcriptomic analysis identified 1229 and 800 differentially expressed genes respectively in OGD and OGD/R comparisons. Enrichment analysis highlighted ribosome, endoplasmic reticulum, and mitochondrial pathways. Six core genes were screened, including RPS7, RPL36A, RPS9, RSL24D1, RPL41, and OSTC, all of which were upregulated under OGD and normalized after reoxygenation. We identified novel ribosome-related genes as potential biomarkers of BBB injury in cerebral infarction. These findings enhance our understanding of BBB pathophysiology and offer new targets for diagnostic and therapeutic strategies in ischemic stroke.

2025-11-27 | GSE311086 | GEO

Promoter competition and Polycomb Response Elements govern transvection efficiency between co-regulated engrailed and invected genes in Drosophila.

Project description:Transvection is a phenomenon where gene regulatory elements interact between different chromosomes, adding an additional layer of regulatory control beyond traditional cis-interactions. Although transvection effects have been characterized for many individual genes in Drosophila, it remains unclear how trans-interactions occur among multiple co-regulated genes where enhancers are shared. Here we demonstrate that transvection is supported at the engrailed-invected (en-inv) locus, where transcription of the two developmental patterning genes is coordinated by common enhancers. Our data show that the presence of the en promoter in cis to the enhancers prevents trans-activation of inv, but removal of this promoter enables robust transvection, demonstrating competition between heterologous promoters in trans. We also find that local Polycomb Response Elements (PREs) enhance transvection reliability but are not strictly required for trans-activation. Furthermore, our analysis reveals that transvection at this locus is developmentally regulated, occurring efficiently in third instar larval tissues and late-stage embryos but not in early embryonic stages. Finally, we show that en-inv transvection can be reconstituted using transgenic constructs at an ectopic chromosomal location where it produces a striking reciprocal expression pattern between en in cis and inv in trans, suggesting that these enhancers can choose to activate one promoter or the other in a stochastic manner.

2025-09-25 | GSE308802 | GEO

RNA-sequencing analysis gene expression changes in response to ischemia reperfusion and upon manipulation of miR-483-5p in PC12 highly differentiated cells

Project description:The consequences of cardiac arrest are often fatal, including brain injury after resuscitation. It has been reported that few people patients can recover to the neurological state before cardiac arrest. MiRNAs are short non-protein-coding RNA molecules that are evolutionarily conserved and ubiquitously expressed. Numerous pieces of research have reviewed the role of miRNAs in regulating neuronal apoptosis, regeneration, and plasticity of neurons, and inflammatory after cardiac arrest . As the stability of miRNAs in the bloodstream and the function in the regulation of neurological impairment after ischemia-reperfusion injury, microRNAs have been the most potential new biomarkers and therapeutic targets after cardiac arrest to alleviate neurological impairment . In this work, we found that the level of miR-483-5p is correlated to the prognosis of neurological function. To investigate the function of miR-483-5p on neurons after ischemia-reperfusion injury,we established highly differentiated PC12 cell lines in which miR-483-5p was overexpressed by transfection with miR-483-5p mimcis.We then performed gene expression profiling analysis using data obtained from RNA-seq of PC12 cells in different groups.

2022-07-25 | GSE209531 | GEO

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