Increasing evidence indicates that metabolic disorders in offspring can result from the father's diet, but the mechanism remains unclear. In a paternal mouse model given a high-fat diet (HFD), we ...showed that a subset of sperm transfer RNA–derived small RNAs (tsRNAs), mainly from 5’ transfer RNA halves and ranging in size from 30 to 34 nucleotides, exhibited changes in expression profiles and RNA modifications. Injection of sperm tsRNA fractions from HFD males into normal zygotes generated metabolic disorders in the F₁ offspring and altered gene expression of metabolic pathways in early embryos and islets of F₁ offspring, which was unrelated to DNA methylation at CpG-enriched regions. Hence, sperm tsRNAs represent a paternal epigenetic factor that may mediate intergenerational inheritance of diet-induced metabolic disorders.
The discovery of RNAs (for example, messenger RNAs, non-coding RNAs) in sperm has opened the possibility that sperm may function by delivering additional paternal information aside from solely ...providing the DNA
. Increasing evidence now suggests that sperm small non-coding RNAs (sncRNAs) can mediate intergenerational transmission of paternally acquired phenotypes, including mental stress
and metabolic disorders
. How sperm sncRNAs encode paternal information remains unclear, but the mechanism may involve RNA modifications. Here we show that deletion of a mouse tRNA methyltransferase, DNMT2, abolished sperm sncRNA-mediated transmission of high-fat-diet-induced metabolic disorders to offspring. Dnmt2 deletion prevented the elevation of RNA modifications (m
C, m
G) in sperm 30-40 nt RNA fractions that are induced by a high-fat diet. Also, Dnmt2 deletion altered the sperm small RNA expression profile, including levels of tRNA-derived small RNAs and rRNA-derived small RNAs, which might be essential in composing a sperm RNA 'coding signature' that is needed for paternal epigenetic memory. Finally, we show that Dnmt2-mediated m
C contributes to the secondary structure and biological properties of sncRNAs, implicating sperm RNA modifications as an additional layer of paternal hereditary information.
Cellular senescence is associated with renal disease progression, and accelerated tubular cell senescence promotes the pathogenesis of renal fibrosis. However, the underlying mechanism is unknown. We ...assessed the potential role of Wnt9a in tubular cell senescence and renal fibrosis. Compared with tubular cells of normal subjects, tubular cells of humans with a variety of nephropathies and those of several mouse models of CKD expressed high levels of Wnt9a that colocalized with the senescence-related protein p16
Wnt9a expression level correlated with the extent of renal fibrosis, decline of eGFR, and expression of p16
Furthermore, ectopic expression of Wnt9a after ischemia-reperfusion injury (IRI) induced activation of
-catenin and exacerbated renal fibrosis. Overexpression of Wnt9a exacerbated tubular senescence, evidenced by increased detection of p16
expression and senescence-associated
-galactosidase activity. Conversely, shRNA-mediated knockdown of Wnt9a repressed IRI-induced renal fibrosis
and impeded the growth of senescent tubular epithelial cells in culture. Notably, Wnt9a-induced renal fibrosis was inhibited by shRNA-mediated silencing of p16
in the IRI mouse model. In a human proximal tubular epithelial cell line and primary renal tubular cells, Wnt9a remarkably upregulated levels of senescence-related p16
, p19
, p53, and p21 and decreased the phosphorylation of retinoblastoma protein. Wnt9a also induced senescent tubular cells to produce TGF-
1, which promoted proliferation and activation in normal rat kidney fibroblasts. Thus, Wnt9a drives tubular senescence and fibroblast activation. Furthermore, the Wnt9a-TGF-
pathway appears to create a reciprocal activation loop between senescent tubular cells and activated fibroblasts that promotes and accelerates the pathogenesis of renal fibrosis.
Although high-throughput RNA sequencing (RNA-seq) has greatly advanced small non-coding RNA (sncRNA) discovery, the currently widely used complementary DNA library construction protocol generates ...biased sequencing results. This is partially due to RNA modifications that interfere with adapter ligation and reverse transcription processes, which prevent the detection of sncRNAs bearing these modifications. Here, we present PANDORA-seq (panoramic RNA display by overcoming RNA modification aborted sequencing), employing a combinatorial enzymatic treatment to remove key RNA modifications that block adapter ligation and reverse transcription. PANDORA-seq identified abundant modified sncRNAs-mostly transfer RNA-derived small RNAs (tsRNAs) and ribosomal RNA-derived small RNAs (rsRNAs)-that were previously undetected, exhibiting tissue-specific expression across mouse brain, liver, spleen and sperm, as well as cell-specific expression across embryonic stem cells (ESCs) and HeLa cells. Using PANDORA-seq, we revealed unprecedented landscapes of microRNA, tsRNA and rsRNA dynamics during the generation of induced pluripotent stem cells. Importantly, tsRNAs and rsRNAs that are downregulated during somatic cell reprogramming impact cellular translation in ESCs, suggesting a role in lineage differentiation.
Nitenpyram is a neonicotinoid insecticide that is commonly found in the environment. However, its biodegradation by pure cultures of bacteria has not been widely investigated and the catabolic ...pathway (s) for nitenpyram metabolism remain elusive. In this study, the aerobic strain DF-1, isolated from a wastewater-treatment pool contaminated with nitenpyram. The strain was designated an
sp. utilizing a combination of traditional methods and molecular ones. Strain DF-1 can use nitenpyram as a sole carbon or nitrogen source for growth. In liquid medium, 100 mg·L
nitenpyram was metabolized to undetectable levels within 10 days. Four metabolites were found by gas chromatography-mass spectrometry (GC-MS) analyses during nitenpyram degradation. According to the aforementioned data, a partial metabolic pathway of nitenpyram was proposed of strain DF-1. Inoculation of strain DF-1 promoted nitenpyram (10 mg·kg
) degradation in either sterile or non-sterile soil. To our knowledge, this is the first characterization of nitenpyram degradation by a specific bacterium and likely to be exploited for the remediation of nitenpyram-contaminated sites.
A recent study led by Professor Rob Martienssen in Cell showed that 3＇-tRNA-derived small RNAs can suppress long terminal repeat ret- rotransposon activity in mammalian cells by mechanisms ...independent of DNA-associated epigenetic marks, suggesting how the genome may defend itself from retrotransposon invasion during epigenetic repro- gramming.
The heterogeneity of mesenchymal stem cells (MSCs) is poorly understood, thus limiting clinical application and basic research reproducibility. Advanced single-cell RNA sequencing (scRNA-seq) is a ...robust tool used to analyse for dissecting cellular heterogeneity. However, the comprehensive single-cell atlas for human MSCs has not been achieved.
This study used massive parallel multiplexing scRNA-seq to construct an atlas of > 130 000 single-MSC transcriptomes across multiple tissues and donors to assess their heterogeneity. The most widely clinically utilised tissue resources for MSCs were collected, including normal bone marrow (n = 3), adipose (n = 3), umbilical cord (n = 2), and dermis (n = 3).
Seven tissue-specific and five conserved MSC subpopulations with distinct gene-expression signatures were identified from multiple tissue origins based on the high-quality data, which has not been achieved previously. This study showed that extracellular matrix (ECM) highly contributes to MSC heterogeneity. Notably, tissue-specific MSC subpopulations were substantially heterogeneous on ECM-associated immune regulation, antigen processing/presentation, and senescence, thus promoting inter-donor and intra-tissue heterogeneity. The variable dynamics of ECM-associated genes had discrete trajectory patterns across multiple tissues. Additionally, the conserved and tissue-specific transcriptomic-regulons and protein-protein interactions were identified, potentially representing common or tissue-specific MSC functional roles. Furthermore, the umbilical-cord-specific subpopulation possessed advantages in immunosuppressive properties.
In summary, this work provides timely and great insights into MSC heterogeneity at multiple levels. This MSC atlas taxonomy also provides a comprehensive understanding of cellular heterogeneity, thus revealing the potential improvements in MSC-based therapeutic efficacy.
Venous thromboembolism(VTE)is a common multifactorial disease. Anticoagulant protein deficiency is the most usual hereditary thrombophilia in the Chinese people, which includes protein C(PC), protein ...S and antithrombin deficiencies.
A retrospective analysis was conducted on clinical manifestations, laboratory tests, genetic information, and other relevant data of siblings diagnosed with VTE in 2020 at the Department of Pediatrics of Shenzhen Second People's Hospital. The proband, a 12-year-old female, was admitted to the hospital in December 2020 with a complaint of pain in the left lower limb for four days. The examination found that the PC activity was 53%, and B-ultrasound showed bilateral thrombosis of the great saphenous vein in the thigh segment. The proband's younger brother, a 10-year-old male, was admitted to the hospital in January 2021 due to right lower limb pain for two weeks. PC activity is 40%. B-ultrasound showed superficial venous thrombosis in the left lower limb and upper limb. Both siblings suffered from thalassemia and underwent splenectomy before recurrent thrombosis occurred. The proband's mother was asymptomatic, and her PC activity was 45%. Both cases were treated with warfarin anticoagulation, and their symptoms improved. The proband's mother was found to have a heterozygous mutation at this locus through Sanger sequencing.
Protein C deficiency should be considered for venous thromboembolism in childhood. The heterozygous mutation 1204 A > G in PROC exon 9 in this family is reported for the first time.
Silicon nanowires (SiNWs) with excellent light trapping properties have been widely applied in photovoltaic devices, which provide opportunities for boosting the photons harvested by Si. However, the ...photoexcited carriers are easily trapped and recombined by high-density surface defects due to higher surface area prolonging to depth of nanowire. In this work, in order to reduce the surface defects and recombination rate of SiNWs, a simple solution process is used to modify the surface structure. Applying the tetramethyl ammonium hydroxide (TMAH) treatment leads to smooth and taper Si NW surface, which improves the open-circuit voltage (
V
oc
) and fill factor (FF) obviously. Thus, a champion PCE of 14.08% is achieved for the nanostructured Si/PEDOT:PSS hybrid device by 60-s TMAH treatment. It also indicates that TMAH treatment promises a simple and effective method for enhancing Si NW-based devices.
Leaf angle is an important agronomic trait in maize
Zea mays
L.. The compact plant phenotype, with a smaller leaf angle, is suited for high-density planting and thus for increasing crop yields. ...Here, we studied the ethyl methane sulfonate (EMS)-induced mutant
bhlh112
. Leaf angle and plant height were significantly decreased in
bhlh112
compared to the wild-type plants. After treatment of seedlings with exogenous IAA and ABA respectively, under the optimal concentration of exogenous hormones, the variation of leaf angle of the mutant was more obvious than that of the wild-type, which indicated that the mutant was more sensitive to exogenous hormones. Transcriptome analysis showed that the
ZmbHLH112
gene was related to the biosynthesis of auxin and brassinosteroids, and involved in the activation of genes related to the auxin and brassinosteroid signal pathways as well as cell elongation. Among the GO enrichment terms, we found many differentially expressed genes (DEGs) enriched in the cell membrane and ribosomal biosynthesis, hormone biosynthesis and signaling pathways, and flavonoid biosynthesis, which could influence cell growth and the level of endogenous hormones affecting leaf angle. Therefore,
ZmbHLH112
might regulate leaf angle development through the auxin signaling and the brassinosteroid biosynthesis pathways. 12 genes related to the development of leaf were screened by WGCNA; In GO enrichment and KEGG pathways, the genes were mainly enriched in rRNA binding, ribosome biogenesis, Structural constituent of ribosome;
Arabidopsis
ribosome RNA methyltransferase CMAL is involved in plant development, likely by modulating auxin derived signaling pathways; The free 60s ribosomes and polysomes in the functional defective mutant
rice minute-like1
(
rml1
) were significantly reduced, resulting in plant phenotypic diminution, narrow leaves, and growth retardation; Hence, ribosomal subunits may play an important role in leaf development. These results provide a foundation for further elucidation of the molecular mechanism of the regulation of leaf angle in maize.
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