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Stroke-brain infiltrating stem cells - mouse

ABSTRACT: Genes upregulated in stroke infiltrating stem cells were compared against the parent non-infiltrated mouse stem cell line derived from immortomouseTM. Abstract Background and Purpose- Although the therapeutic potential of bone marrow-derived stem cells (SC) has been addressed in different experimental models of ischemic stroke, it is still unclear how SC induce neuroprotection following stroke. In this study, we describe a novel method for recovering SC infiltrating post-stroke brain tissue allowing the determination of genes which become persistently activated / or depressed (compared to their naïve counterparts) during SC-mediated neuroprotection. Methods- Ischemic stroke was induced in C57BL/6 mice by middle cerebral artery occlusion for 1 h, followed by reperfusion. SC were isolated from H-2Kb-tsA58 (immortomouseTM) mice, and were administered (i.v.) 24 h after reperfusion. At the onset of therapeutic improvement (14 days after ischemia), infarcted brain tissue was isolated and infarct-infiltratng SC cultured at 33°C. Microarray analysis and RT-PCR were performed to compare persistent differential gene expression between naïve and infiltrating SC populations. Results- Z-scoring revealed dramatic changes in extracellular genes of analyzed cells. Pair-wise analysis detected 80 extracellular factor genes that were up-regulated ( 2 fold, P<0.05, Benjamini-Hochberg correction) between naïve and infiltrated SC. Although several conventional neuroregenerative, nerve guidance and angiogenic factors (bFGF, bone morphogenetic protein, angiopoietins, neural growth factors were among the expressed genes detected we identified Cytokine receptor-like factor 1 (Crlf1), Fgf7, family with sequence similarity 19, member A5 (Fam19a5), Glypican 1 (Gpc1), Dickkopf homolog 2 (Dkk2), Endothelial cell-specific molecule 1, Osteopontin (OPN)35, Tissue factor pathway inhibitor 2, Masp3 mRNA for MBL-associated serine protease-3, Glial cell line derived neurotrophic factor (Gdnf), Bone morphogenetic protein 2 (Bmp2), Olfactomedin 1, Sushi-repeat-containing protein, X-linked 2 (Srpx2). Conclusions- SC infiltrating the post-i schemic brain assume a persistently altered pattern of expressed extracellular genes compared to naïve SC that contributes to neuroprotection, regeneration and angiogenesis in infarcts. Keywords: Gene activation / suppression study

ORGANISM(S): Mus musculus

PROVIDER: GSE21393 | GEO | 2010/12/31

SECONDARY ACCESSION(S): PRJNA126393

REPOSITORIES: GEO

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Project description:Genes upregulated in stroke infiltrating stem cells were compared against the parent non-infiltrated mouse stem cell line derived from immortomouseTM. Abstract Background and Purpose- Although the therapeutic potential of bone marrow-derived stem cells (SC) has been addressed in different experimental models of ischemic stroke, it is still unclear how SC induce neuroprotection following stroke. In this study, we describe a novel method for recovering SC infiltrating post-stroke brain tissue allowing the determination of genes which become persistently activated / or depressed (compared to their naïve counterparts) during SC-mediated neuroprotection. Methods- Ischemic stroke was induced in C57BL/6 mice by middle cerebral artery occlusion for 1 h, followed by reperfusion. SC were isolated from H-2Kb-tsA58 (immortomouseTM) mice, and were administered (i.v.) 24 h after reperfusion. At the onset of therapeutic improvement (14 days after ischemia), infarcted brain tissue was isolated and infarct-infiltratng SC cultured at 33°C. Microarray analysis and RT-PCR were performed to compare persistent differential gene expression between naïve and infiltrating SC populations. Results- Z-scoring revealed dramatic changes in extracellular genes of analyzed cells. Pair-wise analysis detected 80 extracellular factor genes that were up-regulated ( 2 fold, P<0.05, Benjamini-Hochberg correction) between naïve and infiltrated SC. Although several conventional neuroregenerative, nerve guidance and angiogenic factors (bFGF, bone morphogenetic protein, angiopoietins, neural growth factors were among the expressed genes detected we identified Cytokine receptor-like factor 1 (Crlf1), Fgf7, family with sequence similarity 19, member A5 (Fam19a5), Glypican 1 (Gpc1), Dickkopf homolog 2 (Dkk2), Endothelial cell-specific molecule 1, Osteopontin (OPN)35, Tissue factor pathway inhibitor 2, Masp3 mRNA for MBL-associated serine protease-3, Glial cell line derived neurotrophic factor (Gdnf), Bone morphogenetic protein 2 (Bmp2), Olfactomedin 1, Sushi-repeat-containing protein, X-linked 2 (Srpx2). Conclusions- SC infiltrating the post-i schemic brain assume a persistently altered pattern of expressed extracellular genes compared to naïve SC that contributes to neuroprotection, regeneration and angiogenesis in infarcts. Keywords: Gene activation / suppression study Comparison of persistent stem cell gene expression induced by stroke-infarct infiltration

Project description:Prenatal alcohol exposure (PAE) is linked to elevated risk for systemic adult-onset diseases like hypertension, impaired glucose and immune regulation, and in animal models, to impaired recovery from acute onset diseases like cerebrovascular ischemic stroke. Recent evidence suggests that the gastrointestinal system rapidly becomes dysbiotic following cerebrovascular stroke, resulting in systemic inflammation. We hypothesized that a history of PAE would modify the systemic effects of stroke, and transduce exposure-dependent transcriptomic changes in downstream sentinel tissues of the enteric portal circulation that have previously been linked to biobehavioral outcomes in rodent PAE models. Pregnant Sprague Dawley rats were exposed to repeated episodes of vaporized ethanol or room air from gestational day 8 to 19. At 5 months, progeny from each treatment condition were subjected to unilateral endothelin-1 induced occlusion of the middle cerebral artery and outcomes evaluated after 2 days while other progeny stayed stroke-naïve. Stroke induced disabilities were assessed by behavioral assays (adhesive removal, Vibrissae evoked fore-limb placement, circling) and infarct size. The mesenteric adipose tissue and liver transcriptomes were assessed by sequencing, from age-matched stroke-exposed and stroke-naïve offspring. In stroke-naïve animals, pathway analysis identified rRNA processing as downregulated and citric acid cycle as upregulated in mesenteric adipose. Weighted gene correlation network analysis (WGCNA) identified, in the liver of stoke-naïve animals, a moderate but significant correlation between PAE status and necroptosis, a proinflammatory form of programmed cell death (Pearson’s r=0.554, p<0.05). Two days after a stroke, PAE rats exhibited worse neurological scores compared to controls (p<0.05). WGCNA after stroke identified an adipose gene network associated with B cell differentiation and NF-kappa B signaling as moderately correlated with post-stroke neurological function (Pearson's r=0.52, p=0.05). Post-stroke WGCNA also identified a liver proinflammatory gene network strongly correlated with post-stroke neurological function (Pearson's r=-0.63, p<0.01). PAE persistently alters the transcriptome of afferent tissue targets of enteric circulation in adult rat offspring. Moreover, PAE-linked enteric inflammation is correlated to worse outcomes following cerebrovascular ischemic stroke in adulthood. Enteric disturbances may mediate adverse brain health outcomes due to PAE in adulthood.

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Stroke-brain infiltrating stem cells - mouse

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