METHODS/STUDY POPULATION To determine the mechanism by which AURKA inhibitors ameliorate the leukemic phenotype, we have examined the functional requirement for Aurka in adult hematopoiesis.
OBJECTIVES/SPECIFIC AIMS We have recently shown that small molecule inhibitors of Aurora A kinase (AURKA) induce polyploidization and differentiation of normal and malignant megakaryocytes. Northwestern University, Chicago, Illinois, United States DISCUSSION/SIGNIFICANCE OF IMPACT Our results show that MeCP2 regulates important genes for mitochondria, suggesting the importance in investigating the previously less explored function of MeCP2 in energy metabolism.ĪURORA A KINASE IS REQUIRED FOR HEMATOPOIESIS AND COUPLES POLYPLOIDIZATION WITH TERMINAL DIFFERENTIATION IN MEGAKARYOCYTES THROUGH PHOSPHORYLATION OF NF‐E2īenjamin Goldenson, Q. Gene sets that were known to highly express in Parkinson's diseases and Huntington's diseases were also found to be highly expressed in neurons from MeCP2 mutant RTT‐iPSCs. RESULTS/ANTICIPATED RESULTS We found that mutant neurons differentiated from RTT‐iPSCs showed aberrant expression of genes involved in mitochondrial functions, including mitochondrial ribosomal proteins and proteins for electron transports. The publicly available transcriptome data from RTT patients brains and immortalized B lymphoid cell lines were obtained and used for comparative analysis with our data sets. These genes were used to determine the cellular signaling pathways affected in MeCP2 mutant neurons. Pairwise comparison was performed to identify differentially expressed genes between wild‐type and mutant neurons. Transcriptomes were obtained by RNA‐seq in iPSCs and neurons. METHODS/STUDY POPULATION iPSC clones expressing wild‐type MeCP2 (RTT‐wt‐iPSCs), mutated MeCP2 (RTT‐mu‐iPSCs) or both (RTT‐bi‐iPSCs) were differentiated into neurons. This study aims to investigate the function of MeCP2 in human neurons. Using reprogramming technology, we isolated induced pluripotent stem (iPS) cells from RTT patients’ somatic cells. Following the normal development until 6–18 months, classic RTT patients show the symptoms, such as loss of language and motor milestone, purposeful hand movement, and normal head growth. Mutations in methyl CpG binding protein 2 (MeCP2) that is present in Xq28 locus are mainly responsible for RTT. OBJECTIVES/SPECIFIC AIMS Rett syndrome (RTT) is one of the most prevalent female neurodevelopmental disorders that cause severe mental retardation. Yale University, New Haven, Connecticut, United States ABERRANT EXPRESSION OF MITOCHONDRIAL GENES IN RETT SYNDROME CELLS
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