Identifying cadmium and lead co-accumulation from living rice blade spectrum.

Neither cadmium (Cd) nor lead (Pb) is necessary for crop growth, but they both can accumulate in soil and crop tissues, resulting in land degradation and crop reduction. Few researchers have explored how to detect Cd-Pb co-accumulation in leaves using proximal sensing techniques, especially by low-cost, easy-to-use leaf clips that capture hyperspectral reflections at suitable foliar positions. In this study, a hyperspectral imager was employed to collect images of the rice canopy from a designed greenhouse experiment that included 16 pretreatments of Cd-Pb co-accumulation, followed by spectral extractions from 3 foliar positions: the blade root, the middle of the leaf, and the leaf apex. A support vector machine with leave-one-out cross-validation was performed to diagnose the contaminative levels based on the feature wavelengths selected by an improved successive projection algorithm. Partial least squares regression was used to predict Cd-Pb concentrations in rice blades. The results indicated that diagnostic accuracies were varied using spectra of different foliar positions. The blade root and leaf apex of rice blades were the optimal foliar position for detecting Cd and Pb contamination, respectively. At the optimal foliar positions, diagnostic accuracies exceeded 0.80 for distinguishing whether the rice is subject to Cd-Pb contamination. The Cd prediction performed 'very good' with a residual prediction deviation (RPD) of 2.21, a R2 of 0.79, and a root mean square error (RMSE)of 6.14, while that of Pb was 1.62, 0.61, and 186.54. Important wavelengths were identified at 659-694 nm and 667-694 nm to detect Cd and Pb contamination. In summary, our results verified the feasibility and clarified the optimal foliar positions of rice blades to detect Cd-Pb contamination. The wavelengths selecting have the great potential in the design of future leaf clips, and the optimal foliar position can provide suggestions to improve diagnostic performances in field applications.

TREM2hi resident macrophages protect the septic heart by maintaining cardiomyocyte homeostasis.

Sepsis-induced cardiomyopathy (SICM) is common in septic patients with a high mortality and is characterized by an abnormal immune response. Owing to cellular heterogeneity, understanding the roles of immune cell subsets in SICM has been challenging. Here we identify a unique subpopulation of cardiac-resident macrophages termed CD163+RETNLA+ (Mac1), which undergoes self-renewal during sepsis and can be targeted to prevent SICM. By combining single-cell RNA sequencing with fate mapping in a mouse model of sepsis, we demonstrate that the Mac1 subpopulation has distinct transcriptomic signatures enriched in endocytosis and displays high expression of TREM2 (TREM2hi). TREM2hi Mac1 cells actively scavenge cardiomyocyte-ejected dysfunctional mitochondria. Trem2 deficiency in macrophages impairs the self-renewal capability of the Mac1 subpopulation and consequently results in defective elimination of damaged mitochondria, excessive inflammatory response in cardiac tissue, exacerbated cardiac dysfunction and decreased survival. Notably, intrapericardial administration of TREM2hi Mac1 cells prevents SICM. Our findings suggest that the modulation of TREM2hi Mac1 cells could serve as a therapeutic strategy for SICM.

FTO mediates LINE1 m6A demethylation and chromatin regulation in mESCs and mouse development.

N6-methyladenosine (m6A) is the most abundant internal modification on mammalian messenger RNA. It is installed by a writer complex and can be reversed by erasers such as the fat mass and obesity-associated protein FTO. Despite extensive research, the primary physiological substrates of FTO in mammalian tissues and development remain elusive. Here, we show that FTO mediates m6A demethylation of long-interspersed element-1 (LINE1) RNA in mouse embryonic stem cells (mESCs), regulating LINE1 RNA abundance and the local chromatin state, which in turn modulates the transcription of LINE1-containing genes. FTO-mediated LINE1 RNA m6A demethylation also plays regulatory roles in shaping chromatin state and gene expression during mouse oocyte and embryonic development. Our results suggest broad effects of LINE1 RNA m6A demethylation by FTO in mammals.

NAD+ Modulates the Proliferation and Differentiation of Adult Neural Stem/Progenitor Cells via Akt Signaling Pathway.

Nicotinamide adenine dinucleotide hydrate (NAD+) acts as the essential component of the tricarboxylic citric acid (TCA) cycle and has important functions in diverse biological processes. However, the roles of NAD+ in regulating adult neural stem/progenitor cells (aNSPCs) remain largely unknown. Here, we show that NAD+ exposure leads to the reduced proliferation and neuronal differentiation of aNSPCs and induces the apoptosis of aNSPCs. In addition, NAD+ exposure inhibits the morphological development of neurons. Mechanistically, RNA sequencing revealed that the transcriptome of aNSPCs is altered by NAD+ exposure. NAD+ exposure significantly decreases the expression of multiple genes related to ATP metabolism and the PI3k-Akt signaling pathway. Collectively, our findings provide some insights into the roles and mechanisms in which NAD+ regulates aNSPCs and neuronal development.

Emerging Roles of N6-Methyladenosine Modification in Neurodevelopment and Neurodegeneration.

N6-methyladenosine (m6A), the most abundant modification in messenger RNAs (mRNAs), is deposited by methyltransferases ("writers") Mettl3 and Mettl14 and erased by demethylases ("erasers") Fto and Alkbh5. m6A can be recognized by m6A-binding proteins ("readers"), such as Yth domain family proteins (Ythdfs) and Yth domain-containing protein 1 (Ythdc1). Previous studies have indicated that m6A plays an essential function in various fundamental biological processes, including neurogenesis and neuronal development. Dysregulated m6A modification contributes to neurological disorders, including neurodegenerative diseases. In this review, we summarize the current knowledge about the roles of m6A machinery, including writers, erasers, and readers, in regulating gene expression and the function of m6A in neurodevelopment and neurodegeneration. We also discuss the perspectives for studying m6A methylation.

Fto-modulated lipid niche regulates adult neurogenesis through modulating adenosine metabolism.

Adult neurogenesis is regulated by diverse factors including the local environment, i.e. the neurogenic niche. However, whether the lipid in the brain regulates adult neurogenesis and related mechanisms remains largely unknown. In the present study, we found that lipid accumulates in the brain during postnatal neuronal development. Conditional knockout of Fto (cKO) in lipid not only reduced the level of lipid in the brain but also impaired the learning and memory of mice. In addition, Fto deficiency in lipid did not affect the proliferation of adult neural stem cells (aNSCs), but it did inhibit adult neurogenesis by inducing cell apoptosis. Mechanistically, specific deleting Fto in lipid altered gene expression and increased adenosine secretion of adipocytes. The treatment of adenosine promoted the apoptosis of newborn neurons. As a whole, these results reveal the important function of the lipid niche and its associated mechanism in regulating adult neurogenesis.

O-GlcNAcylation regulates the methionine cycle to promote pluripotency of stem cells.

Methionine metabolism is critical for the maintenance of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) pluripotency. However, little is known about the regulation of the methionine cycle to sustain ESC pluripotency. Here, we show that adenosylhomocysteinase (AHCY), an important enzyme in the methionine cycle, is critical for the maintenance and differentiation of mouse embryonic stem cells (mESCs). We show that mESCs exhibit high levels of methionine metabolism, whereas decreasing methionine metabolism via depletion of AHCY promotes mESCs to differentiate into the three germ layers. AHCY is posttranslationally modified with an O-linked ß-N-acetylglucosamine sugar (O-GlcNAcylation), which is rapidly removed upon differentiation. O-GlcNAcylation of threonine 136 on AHCY increases its activity and is important for the maintenance of trimethylation of histone H3 lysine 4 (H3K4me3) to sustain mESC pluripotency. Blocking glycosylation of AHCY decreases the ratio of S-adenosylmethionine versus S-adenosylhomocysteine (SAM/SAH), reduces the level of H3K4me3, and poises mESC for differentiation. In addition, blocking glycosylation of AHCY reduces somatic cell reprogramming. Thus, our findings reveal a critical role of AHCY and a mechanistic understanding of O-glycosylation in regulating ESC pluripotency and differentiation.

m6A Regulates Neurogenesis and Neuronal Development by Modulating Histone Methyltransferase Ezh2.

N6-methyladenosine (m6A), catalyzed by the methyltransferase complex consisting of Mettl3 and Mettl14, is the most abundant RNA modification in mRNAs and participates in diverse biological processes. However, the roles and precise mechanisms of m6A modification in regulating neuronal development and adult neurogenesis remain unclear. Here, we examined the function of Mettl3, the key component of the complex, in neuronal development and adult neurogenesis of mice. We found that the depletion of Mettl3 significantly reduced m6A levels in adult neural stem cells (aNSCs) and inhibited the proliferation of aNSCs. Mettl3 depletion not only inhibited neuronal development and skewed the differentiation of aNSCs more toward glial lineage, but also affected the morphological maturation of newborn neurons in the adult brain. m6A immunoprecipitation combined with deep sequencing (MeRIP-seq) revealed that m6A was predominantly enriched in transcripts related to neurogenesis and neuronal development. Mechanistically, m6A was present on the transcripts of histone methyltransferase Ezh2, and its reduction upon Mettl3 knockdown decreased both Ezh2 protein expression and consequent H3K27me3 levels. The defects of neurogenesis and neuronal development induced by Mettl3 depletion could be rescued by Ezh2 overexpression. Collectively, our results uncover a crosstalk between RNA and histone modifications and indicate that Mettl3-mediated m6A modification plays an important role in regulating neurogenesis and neuronal development through modulating Ezh2.