Clinical and molecular characterization of a novel LMX1A frameshift mutation near the C-terminus lead to familial non-syndromic sensorineural hearing loss
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE200599 | GEO | 2025/04/11
REPOSITORIES: GEO
Similar Datasets
Project description:Clinical and molecular characterization of a novel LMX1A frameshift mutation near the C-terminus lead to familial non-syndromic sensorineural hearing loss
| PRJNA825501 | ENA
Project description:We report the RNA expression of the House Ear Institute-Organ of Corti (HEI-OC1) cells with and without cisplatin exposure to identify differencialyy expressed genes. The results of RNA-seq analysis showed 2732 downregulated, and 1639 upregulated genes above 1-fold change in cisplatin threated cells compared to non-treated controls.
2021-07-16 | GSE180141 | GEO
Project description:Cisplatin, a utilized anticancer drug in clinical practice, induces sensorineural hearing loss (SNHL) in patients. However, the precise mechanism underlying cisplatin-associated ototoxicity remains unknown. HEI-OC1 cells are immortalized cells derived from the organs of Corti mice and nuclear factor erythroid 2-related factor 2 （Nrf2） knockout (KO) significantly enhances cisplatin resistance in these cells. The exploration of transcriptomic data from Nrf2 KO has significant implications for the identification of novel targets to enhance HEI-OC1 cisplatin resistance in Nrf2 KO and for understanding the biological characteristics associated with SNHL. The RNA-seq analysis revealed a significant enrichment of differentially expressed genes (DEGs) in the Nrf2 KO model within key signaling pathways, including the PI3K-Akt, MAPK, as well as Glutathione metabolism signaling pathways. Notably, expression levels of 17 specific genes were confirmed by RT-qPCR (Real-time Quantitative-PCR). The biomarkers identified in this study may be key to understanding the biological mechanism by which Nrf2 KO strongly increases HEI-OC1 cisplatin resistance, and by targeting the PI3K-Akt, MAPK, Glutathione metabolism signaling pathways provide new ideas for the prevention and treatment of cisplatin-induced SNHL.
2024-09-01 | GSE268900 | GEO
Project description:Development of the nervous system depends on signaling centers – specialized cellular populations that produce secreted molecules to regulate neurogenesis in the neighboring neuroepithelium. Some signaling centers also generate key types of neurons. The formation of a signaling center involves its induction, the maintenance of expression of its secreted molecules, and cell differentiation and migration events. How these distinct processes are coordinated during signaling center development remains unknown. Here we show that Lmx1a acts as a master regulator to orchestrate the formation and function of the cortical hem (CH), a critical signaling center that controls hippocampus development. Lmx1a co-regulates CH induction, its Wnt signaling, and the differentiation and migration of CH-derived Cajal-Retzius neurons. Combining RNAseq, genetic, and rescue experiments, we identified major downstream genes that mediate distinct Lmx1a-dependent processes. Our work revealed that signaling centers in the mammalian brain employ master regulatory genes and established a framework for analyzing signaling center development.
2023-09-06 | GSE216165 | GEO
Project description:The LIM homeodomain transcription factor Lmx1a is a very potential inducer of stem cells towards dopaminergic neurons. Despite several studies on the function of this gene, the exact in vivo role of Lmx1a in mesodiencephalic dopamine (mdDA) neuronal specification is still not understood. To analyze the genes functioning downstream of Lmx1a, we performed expression microarray analysis of LMX1A overexpressing MN9D dopaminergic cells. Several interesting regulated genes were identified, based on their regulation in other, previously generated expression arrays, and their expression pattern in the developing mdDA neuronal field. Post analysis through in vivo expression analysis in Lmx1a mouse mutant (drJ/drJ) embryos demonstrated a clear decrease in expression of the genes Grb10 and Rgs4, in and adjacent to the rostral and dorsal mdDA neuronal field and within the Lmx1a expression domain. Interestingly, the DA marker Vmat2 was significantly up-regulated as a consequence of increased LMX1A dose, and subsequent analysis on Lmx1a mutant E14.5 and adult tissue revealed a significant decrease in Vmat2 expression in mdDA neurons. Taken together, microarray analysis of an LMX1A overexpression cell system resulted in the identification of novel downstream targets of Lmx1A in mdDA neurons: Grb10, Rgs4 and Vmat2.
2013-01-08 | GSE39174 | GEO
Project description:Despite the progress in safety and efficacy of cell therapy with pluripotent stem cells (PSCs), the presence of residual undifferentiated stem cells or proliferating neural progenitor cells (NPCs) with rostral identity has remained a major challenge. Here we reported the generation of an LMX1A knock-in GFP reporter human embryonic stem cell (hESC) line that marks the early dopaminergic progenitors during neural differentiation. Purified GFP positive cells in vitro exhibited expression of mRNA and proteins that characterized and matched the midbrain dopaminergic identity. Further proteomic analysis of enriched LMX1A+ cells identified several membrane associated proteins including CNTN2, enabling prospective isolation of LMX1A+ progenitor cells. Transplantation of hPSC-derived purified CNTN2+ progenitors enhanced dopamine release from transplanted cells in the host brain and alleviated Parkinson’s disease symptoms in animal models. Our study establishes an efficient approach for purification of large numbers of hPSC-derived dopaminergic progenitors for therapeutic applications.
2018-06-06 | PXD007837 | Pride
Project description:The LIM homeodomain transcription factor Lmx1a is a very potential inducer of stem cells towards dopaminergic neurons. Despite several studies on the function of this gene, the exact in vivo role of Lmx1a in mesodiencephalic dopamine (mdDA) neuronal specification is still not understood. To analyze the genes functioning downstream of Lmx1a, we performed expression microarray analysis of LMX1A overexpressing MN9D dopaminergic cells. Several interesting regulated genes were identified, based on their regulation in other, previously generated expression arrays, and their expression pattern in the developing mdDA neuronal field. Post analysis through in vivo expression analysis in Lmx1a mouse mutant (drJ/drJ) embryos demonstrated a clear decrease in expression of the genes Grb10 and Rgs4, in and adjacent to the rostral and dorsal mdDA neuronal field and within the Lmx1a expression domain. Interestingly, the DA marker Vmat2 was significantly up-regulated as a consequence of increased LMX1A dose, and subsequent analysis on Lmx1a mutant E14.5 and adult tissue revealed a significant decrease in Vmat2 expression in mdDA neurons. Taken together, microarray analysis of an LMX1A overexpression cell system resulted in the identification of novel downstream targets of Lmx1A in mdDA neurons: Grb10, Rgs4 and Vmat2. RNA was isolated from MN9D cells. Each experimental sample consisted of a RNA pool derived from 3 separate 10-cm dishes containing Lmx1a overexpressing MN9D cells (transfected with pcDNA3.1(-)-Lmx1a). microarray analysis was performed in triplicate, each experimental sample was hybridized to the same reference pool of RNA derived from 9 10-cm dishes containing control MN9D cells (transfected with empty pcDNA3.1(-)). On each of three microarray samples, dye swap was performed to correct for dye effects.
2013-01-08 | E-GEOD-39174 | biostudies-arrayexpress
Project description:Recent developments in molecular programming of mesodiencephalic dopaminergic (mdDA) neurons have led to the identification of many transcription factors playing a role in mdDA specification. LIM homeodomain transcription factor Lmx1a is essential for chick mdDA development, and for the efficient differentiation of ES-cells towards a dopaminergic phenotype. In this study, we aimed towards a more detailed understanding of the subtle phenotype in Lmx1a-dr/dr mice. Therefore, microarray analysis was performed, to elucidate the exact molecular programming underlying the neuronal deficits after loss of Lmx1a. Subsequent expression analysis confirmed that Nurr1 is regulated by Lmx1a, and additional downstream targets were identified, like Pou4f1, Pbx1, Pitx2, C130021l20Rik, Calb2 and Rspo2. In line with a specific, rostral-lateral loss of expression of most of these genes during development, Nurr1 and C130021l20Rik were affected in the SNc of the mature mdDA system. Interestingly, this deficit was marked by the complete loss of the Wnt/b-catenin signaling activator Rspo2 in this domain. Expression analysis in Rspo2-/- embryos revealed affected mdDA neurons, partially phenocopying the Lmx1a mutant. Together, in this study we reveal that Lmx1a is essential for a rostral-lateral subset of the mdDA neuronal field, where it might serve a critical function in modulating proliferation and differentiation of mdDA progenitors through the activation of the Wnt activator Rspo2.
2013-12-13 | GSE45831 | GEO
Project description:Recent developments in molecular programming of mesodiencephalic dopaminergic (mdDA) neurons have led to the identification of many transcription factors playing a role in mdDA specification. LIM homeodomain transcription factor Lmx1a is essential for chick mdDA development, and for the efficient differentiation of ES-cells towards a dopaminergic phenotype. In this study, we aimed towards a more detailed understanding of the subtle phenotype in Lmx1a-dr/dr mice. Therefore, microarray analysis was performed, to elucidate the exact molecular programming underlying the neuronal deficits after loss of Lmx1a. Subsequent expression analysis confirmed that Nurr1 is regulated by Lmx1a, and additional downstream targets were identified, like Pou4f1, Pbx1, Pitx2, C130021l20Rik, Calb2 and Rspo2. In line with a specific, rostral-lateral loss of expression of most of these genes during development, Nurr1 and C130021l20Rik were affected in the SNc of the mature mdDA system. Interestingly, this deficit was marked by the complete loss of the Wnt/b-catenin signaling activator Rspo2 in this domain. Expression analysis in Rspo2-/- embryos revealed affected mdDA neurons, partially phenocopying the Lmx1a mutant. Together, in this study we reveal that Lmx1a is essential for a rostral-lateral subset of the mdDA neuronal field, where it might serve a critical function in modulating proliferation and differentiation of mdDA progenitors through the activation of the Wnt activator Rspo2. Microarray expression study comparing 4 samples of homozygous LMX1A dr/dr mice, midbrain E12.5 with a pooled sample of their wt/wt littermates. Two samples were analyzed in opposite dye orientation.
2013-12-13 | E-GEOD-45831 | biostudies-arrayexpress