Project description:To investigate the molecular mechanism for the elimination of leukemia cells after Dox induced OSKM expression, we sorted MLL-AF9 leukemia cells from Dox untreated and treated groups (48h and 72h) leukemic mice for gene expression profiling analysis.
Project description:This paper presents a T-cell receptor (TCR) reactive to the recurrent D835Y driver mutation in the FLT3 tyrosine-kinase domain. TCRFLT3D/Y-redirected T cells selectively eliminated primary human AML cells harboring the D835Y mutation in vitro and in vivo. The TCRFLT3D/Y cells rejected both CD34+ and CD34- AML in mice engrafted with primary leukemia from patients, reaching minimal residual disease negative levels, and eliminated primary CD34+ AML leukemia-propagating cells in vivo. Thus, T cells targeting a single shared mutation can provide efficient immunotherapy towards selective elimination of clonally involved primary AML cells in vivo.
Project description:The ciliated protozoan Tetrahymena undergoes extensive programmed DNA elimination when the germline micronucleus produces the new macronucleus during sexual reproduction. DNA elimination is epigenetically controlled by DNA sequences of the parental macronuclear genome, and this epigenetic regulation is mediated by small RNAs (scnRNAs) of approximately 28-30 nucleotides that are produced and function by an RNAi-related mechanism. Here, we examine scnRNA production and turnover by deep sequencing. scnRNAs are produced exclusively from the micronucleus and non-homogeneously from a variety of chromosomal locations. scnRNAs are preferentially derived from the eliminated sequences, and this preference is mainly determined at the level of transcription. Despite this bias, a significant fraction of scnRNAs is also derived from the macronuclear-destined sequences, and these scnRNAs are degraded during the course of sexual reproduction. These results indicate that the pattern of DNA elimination in the new macronucleus is shaped by the biased transcription in the micronucleus and by the selective degradation of scnRNAs in the parental macronucleus. GRO-Seq and Examination of siRNAs in wild-type,nullisomic 4, EMA1 KO, and TWI1 KO Tetrahymena cells
Project description:The target deletion of ATP binding cassette subfamily member 1 (ABCA1) and G1 (ABCG1) in myeloid cells leads to subretinal drusenoid deposits in mice (Abca1/g1 -m/-m). We here report the selective elimination of p16-positive cells results in the significant eduction in myeloid markers, pro-inflammatory cytokines and prostaglandin biosynthetic enzymes.
Project description:We used RNA-seq to evaluate the global programme of gene expression after Dox inducible Yamanaka factors ectopic expression during this biological process.
Project description:We used ATAC-seq to evaluate the global programme of chromtain accessibility after Dox inducible Yamanaka factors ectopic expression during this biological process.
Project description:The ciliated protozoan Tetrahymena undergoes extensive programmed DNA elimination when the germline micronucleus produces the new macronucleus during sexual reproduction. DNA elimination is epigenetically controlled by DNA sequences of the parental macronuclear genome, and this epigenetic regulation is mediated by small RNAs (scnRNAs) of approximately 28-30 nucleotides that are produced and function by an RNAi-related mechanism. Here, we examine scnRNA production and turnover by deep sequencing. scnRNAs are produced exclusively from the micronucleus and non-homogeneously from a variety of chromosomal locations. scnRNAs are preferentially derived from the eliminated sequences, and this preference is mainly determined at the level of transcription. Despite this bias, a significant fraction of scnRNAs is also derived from the macronuclear-destined sequences, and these scnRNAs are degraded during the course of sexual reproduction. These results indicate that the pattern of DNA elimination in the new macronucleus is shaped by the biased transcription in the micronucleus and by the selective degradation of scnRNAs in the parental macronucleus.