Project description:We recently developed a new model of renal agenesis [i.e., the heterogeneous stock derived model of unilateral renal agenesis, (HSRA)]. The HSRA model consistently exhibits unilateral renal agenesis ranging from 50-75% in each generation and is characterized by low nephron number, early kidney hypertrophy, and an inherent susceptibility to develop significant kidney injury and decline in renal function with age. Whole transcriptome analysis was evaluated at month 1 to identify early changes in genes/networks that may be involved in increased susceptibility of HSRA-S to develop kidney injury in the long-term.
Project description:We recently developed a new model of renal agenesis [i.e., the heterogeneous stock derived model of unilateral renal agenesis, (HSRA)]. The HSRA model consistently exhibits unilateral renal agenesis ranging from 50-75% in each generation and is characterized by low nephron number, early kidney hypertrophy, and an inherent susceptibility to develop significant kidney injury and decline in renal function with age. Whole transcriptome analysis was evaluated at month 1 to identify early changes in genes/networks that may be involved in increased susceptibility of HSRA-S to develop kidney injury in the long-term. An n=4 per group (independent samples) were evaluated for HSRA-S (congenital solitary kidney) and HSRA-C (two-kidney). HSRA-C (two-kidney) samples were set as the control.
Project description:Functional investigation of the role primate-specific gene ZNF808 over pancreas differentiation. Loss of function of ZNF808 is a cause of pancreatic agenesis, which is a failure of pancreas development.
Project description:Although mechanisms underlying early steps in cerebellar development are known, evidence is lacking on genetic and epigenetic changes during the establishment of the synaptic circuitry. Using metagene analysis, we report pivotal changes in multiple reactomes of epigenetic pathway genes in cerebellar granule cells (GCs) during circuit formation. During this stage, Tet genes are up-regulated and vitamin C activation of Tet enzymes increases the levels of 5-hydroxymethylcytosine (5hmC) at exon start sites of up-regulated genes, notably axon guidance genes and ion channel genes. Knockdown of Tet1 and Tet3 by RNA interference in ex vivo cerebellar slice cultures inhibits dendritic arborization of developing GCs, a critical step in circuit formation. These findings demonstrate a role for Tet genes and chromatin remodeling genes in the formation of cerebellar circuitry. 5hmC-enriched genomic DNA fragments were purified with a selective labeling strategy known as hMe-Seal and carried out DNA deep sequencing using Illumina HiSeq 2500.
Project description:Australian working Kelpie dogs are known to be affected with an autosomal recessive form of inherited cerebellar ataxia (cerebellar abiotrophy, CA) that is characterised by a degeneration of Purkinje and granule cells in the cerebellar cortex. The clinical signs of CA include cerebellar ataxia, head tremor, motor in-coordination, wide based stance and high stepping gait, with varied clinical onset age. The clinical and pathological features are similar to cerebellar ataxias in humans. The genome-wide association study on a group of working Kelpies affected with the later onset form of CA identified a region on chromosome 9 to be strongly associated with the disease phenotype. Homozygosity analysis and whole genome sequencing identified a missense single nucleotide polymorphism, that segregated with the CA phenotype.
Project description:To establish a new model system with which to study cerebellar granule lienage development and disease, human hbNES cells were differentiated to cerebellar granule neurons over a 56 day period.
2023-05-29 | GSE233336 | GEO
Project description:WES data for bilateral renal agenesis family
Project description:Functional investigation of the role primate-specific gene ZNF808 over pancreas differentiation. Loss of function of ZNF808 is a cause of pancreatic agenesis, which is a failure of pancreas development.
Project description:During cerebellar development, the main portion of the cerebellar plate neuroepithelium (NE) gives birth to Purkinje cells and interneurons, while the germinal zone at its dorsal edge, called the rhombic lip (RL), generates granule cells and cerebellar nuclei neurons. However, it remains elusive how these components work together to generate the intricate structure of the cerebellar anlage. In this study, we found that a polarized cerebellar anlage structure self-organizes in three-dimensional (3D) human ES cell (hESC) culture. This NE is capable of differentiating into electrophysiologically functional Purkinje cells. The addition of FGF19 promotes spontaneous generation of dorsoventrally polarized NE structures containing cerebellar and basal plates. Furthermore, further addition of SDF1 promoted the generation of stratified cerebellar plate NE with RL-like germinal zones self-forming at the edge. Thus, hESC-derived cerebellar progenitors exhibit substantial self-organizing potential for generating a polarized structure reminiscent of the early human cerebellar anlage at the first trimester. Examination of mRNA profile in two different treated human ES cells .
