Project description:The effects of DNASE1L3 or DNASE1 deficiency on cfDNA methylation was explored in plasma of mice deficient in these nucleases and in DNASE1L3-deficient humans. Compared to wildtype cfDNA, cfDNA in Dnase1l3-deficient mice was significantly hypomethylated, while cfDNA in Dnase1-deficient mice was hypermethylated. The cfDNA hypomethylation in Dnase1l3-deficient mice was due to increased fragmentation and representation from open chromatin regions (OCRs) and CpG islands (CGIs). These findings were absent in Dnase1-deficient mice.
Project description:The effects of DNASE1L3 or DNASE1 deficiency on cfDNA methylation was explored in plasma of mice deficient in these nucleases and in DNASE1L3-deficient humans. Compared to wildtype cfDNA, cfDNA in Dnase1l3-deficient mice was significantly hypomethylated, while cfDNA in Dnase1-deficient mice was hypermethylated. The cfDNA hypomethylation in Dnase1l3-deficient mice was due to increased fragmentation and representation from open chromatin regions (OCRs) and CpG islands (CGIs). These findings were absent in Dnase1-deficient mice.
Project description:We showed that mice in which Dnase1l3 had been deleted showed aberrations in the fragmentation of plasma DNA. We also observed a change in the ranked frequencies of end motifs of plasma DNA caused by the Dnase1l3 deletion.
Project description:This study investigates the impact of DNASE1L3 deficiency on hepatic immune–metabolic homeostasis using TMT-based quantitative proteomics. Liver tissues from 8-week-old wild-type (WT) and DNASE1L3 knockout (KO) mice were analyzed by LC-MS/MS. Differential protein expression and pathway enrichment analyses revealed alterations in lipid metabolism, oxidative stress, Kupffer cell polarization, and ferroptosis, supporting a role for DNASE1L3 in regulating hepatic immune–metabolic stability.
Project description:Recent advances in small RNA research reveal that noncanonical small RNAs, such as tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNAs), are more abundant than well-known microRNAs in various tissue/cell types. Distinct fragmentation of parental RNAs (e.g., tRNA and rRNA) can generate functionally diverse small RNAs. Therefore, we propose a computational tool (qMAP) to identify differential fragmentation of parental RNAs between different biological conditions. Using qMAP, we tested aging-associated differential RNA fragmentation in mouse sperm heads between young and old mice. 28S rRNA was found to exhibit the most significant differential fragmentation. One short rsRNA candidate (17-nt) and one long rsRNA candidate (44-nt) were selected as their involvement of the observed differential fragmentation of 28S rRNA. These two candidate rsRNAs were transfected into mouse embryonic stem cells (mESCs), respectively. mRNA sequencing on these mESCs revealed a distinct transcriptomic response to the 17-nt and 44-nt rsRNAs.
Project description:Noninvasive detection of cancer-associated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing