Journal of Genetics and Genomics最新文献

Pancreatitis is a common gastrointestinal disorder that causes hospitalization with significant morbidity and mortality. The mechanistic pathophysiology of pancreatitis is complicated, limiting the discovery of pharmacological intervention methods. Here, we show that the administration of ATN-161, an antagonist of Integrin-α5, significantly mitigates the pathological condition of acute pancreatitis induced by caerulein. We find that CK19-positive pancreatic ductal cells align parallel to blood vessels in the pancreas. In the caerulein-induced acute pancreatitis model, the newly emergent CK19-positive cells are highly vascularized, with a significant increase in vascular density and endothelial cell number. Single-cell RNA sequencing analysis shows that ductal and endothelial cells are intimate interacting partners, suggesting the existence of a ductal-endothelial interface in the pancreas. Pancreatitis dramatically reduces the crosstalk in the ductal-endothelial interface but promotes the Spp-1/Integrin-α5 signaling. Blocking this signaling with ATN-161 significantly reduces acinar-to-ductal metaplasia, pathological angiogenesis, and restores other abnormal defects induced by caerulein. Our work reveals the therapeutic potential of ATN-161 as an uncharacterized pharmacological method to alleviate the symptoms of pancreatitis.

Nitrogen (N) serves both as a vital macronutrient and a signaling molecule for plants. Unveiling key regulators involved in N metabolism helps dissect the mechanisms underlying N metabolism, which is essential for developing maize with high N use efficiency. Two maize lines, B73 and Ki11, show differential chlorate and low-N tolerance. Time-course transcriptomic analysis reveals that the expression of NUGs in B73 and Ki11 have distinct responsive patterns to nitrate variation. By the coexpression networks, significant differences in the number of N response modules and regulatory networks of transcription factors (TFs) are revealed between B73 and Ki11. There are 23 unique TFs in B73 and 41 unique TFs in Ki11. MADS26 is a unique TF in the B73 N response network, with different expression level and N response pattern in B73 and Ki11. Overexpression of MADS26 enhances the sensitivity to chlorate and the utilization of nitrate in maize, at least partially explaining the differential chlorate tolerance and Low-N sensitivity between B73 and Ki11. The findings in this work provide unique insights and promising candidates for maize breeding to reduce unnecessary N overuse.

Phosphorus (P) is an essential nutrient for crop growth, making it important for maintaining food security as the global population continues to increase. Plants acquire P primarily via the uptake of inorganic phosphate (Pi) in soil through their roots. Pi, which is usually sequestered in soils, is not easily absorbed by plants and represses plant growth. Plants have developed a series of mechanisms to cope with P deficiency. Moreover, P fertilizer applications are critical for maximizing crop yield. Maize is a major cereal crop cultivated worldwide. Increasing its P-use efficiency is important for optimizing maize production. Over the past two decades, considerable progresses have been achieved in research aimed at adapting maize varieties to changes in environmental P supply. Here, we present an overview of the morphological, physiological, and molecular mechanisms involved in P acquisition, translocation, and redistribution in maize and combine the advances in Arabidopsis and rice, to better elucidate the progress of P nutrition. Additionally, we summarize the correlation between P and abiotic stress responses. Clarifying the mechanisms relevant to improving P absorption and use in maize can guide future research on sustainable agriculture.

Pod width influences pod size, shape, yield, and consumer preference in snap beans (Phaseolus vulgaris L.). In this study, we map PvPW1, a quantitative trait locus associated with pod width in snap beans, through genotyping and phenotyping of recombinant plants. We identify Phvul.006G072800, encoding the β-1,3-glucanase 9 protein, as the causal gene for PvPW1. The PvPW1^G3555 allele is found to positively regulate pod width, as revealed by an association analysis between pod width phenotype and the PvPW1^G3555C genotype across 17 bi-parental F₂ populations. 97.7% of the 133 wide pod accessions carry PvPW1^G3555, while 82.1% of the 78 narrow pod accessions carry PvPW1^C3555, indicating strong selection pressure on PvPW1 during common bean breeding. Re-sequencing data from 59 common bean cultivars identify an 8-bp deletion in the intron linked to PvPW1^C3555, leading to the development of the InDel marker of PvM436. Genotyping 317 common bean accessions with PvM436 demonstrated that accessions with PvM436²⁴⁷ and PvM436²²⁷ alleles have wider pods compared to those with PvM436²¹⁹ allele, establishing PvM436 as a reliable marker for molecular breeding in snap beans. These findings highlight PvPW1 as a critical gene regulating pod width and underscore the utility of PvM436 in marker-assisted selection for snap bean breeding.

Williams syndrome (WS) is a rare multisystemic disorder caused by recurrent microdeletions on 7q11.23, characterized by intellectual disability, distinctive craniofacial and dental features, and cardiovascular problems. Previous studies have explored the roles of individual genes within these microdeletions in contributing to WS phenotypes. Here, we report five patients with WS with 1.4 Mb-1.5 Mb microdeletions that include RFC2, as well as one patient with a 167-kb microdeletion involving RFC2 and six patients with intragenic variants within RFC2. To investigate the potential involvement of RFC2 in WS pathogenicity, we generate a rfc2 knockout (KO) zebrafish using CRISPR-Cas9 technology. Additionally, we generate a KO zebrafish of its paralog gene, rfc5, to better understand the functions of these RFC genes in development and disease. Both rfc2 and rfc5 KO zebrafish exhibit similar phenotypes reminiscent of WS, including small head and brain, jaw and dental defects, and vascular problems. RNA-seq analysis reveals that genes associated with neural cell survival and differentiation are specifically affected in rfc2 KO zebrafish. In addition, heterozygous rfc2 KO adult zebrafish demonstrate an anxiety-like behavior with increased social cohesion. These results suggest that RFC2 may contribute to the pathogenicity of Williams syndrome, as evidenced by the zebrafish model.

Plant height and heading date are important agronomic traits in wheat (Triticum aestivum L.) that affect final grain yield. In wheat, knowledge of pseudo-response regulator (PRR) genes on agronomic traits is limited. Here, we identify a wheat TaPRR95 gene by genome-wide association studies to be associated with plant height. Triple allele mutant plants produced by CRISPR/Cas9 show increased plant height, particularly the peduncle, with an earlier heading date. The longer peduncle is mainly caused by the increased cell elongation at its upper section, whilst the early heading date is accompanied by elevated expression of flowering genes, such as TaFT and TaCO1. A peduncle-specific transcriptome analysis reveals up-regulated photosynthesis genes and down-regulated IAA/Aux genes for auxin signaling in prr95^aabbdd plants that may act as a regulatory mechanism to promote robust plant growth. A haplotype analysis identifies a TaPRR95-B haplotype (Hap2) to be closely associated with reduced plant height and increased thousand-grain weight. Moreover, the Hap2 frequency is higher in cultivars than that in landraces, suggesting the artificial selection on the allele during wheat breeding. These findings suggest that TaPRR95 is a regulator for plant height and heading date, thereby providing an important target for wheat yield improvement.

G-protein-coupled receptors (GPCRs) are the largest family of transmembrane receptors and regulate various physiological and pathological processes. Despite extensive studies, the roles of GPCRs in mouse embryonic stem cells (mESCs) remain poorly understood. Here, we show that GPR160, a class A member of GPCRs, is dramatically downregulated concurrent with mESC differentiation into embryoid bodies in vitro. Knockdown of Gpr160 leads to downregulation of the expression of pluripotency-associated transcription factors and upregulation of the expression of lineage markers, accompanying with the arrest of the mESC cell-cycle in the G0/G1 phase. RNA-seq analysis shows that GPR160 participates in the JAK/STAT signaling pathway crucial for maintaining ESC stemness, and the knockdown of Gpr160 results in the downregulation of STAT3 phosphorylation level, which in turn is partially rescued by colivelin, a STAT3 activator. Consistent with these observations, GPR160 physically interacts with JAK1, and cooperates with leukemia inhibitory factor receptor (LIFR) and gp130 to activate the STAT3 pathway. In summary, our results suggest that GPR160 regulates mESC self-renewal and pluripotency by interacting with the JAK1-LIFR-gp130 complex to mediate the JAK1/STAT3 signaling pathway.

Oligoasthenoteratozoospermia is an important factor affecting male fertility and has been found to be associated with genetic factors. However, there are still a proportion of oligoasthenoteratozoospermia cases that cannot be explained by known pathogenic genetic variants. Here, we perform genetic analyses and identify bi-allelic loss-of-function variants of MFSD6L from an oligoasthenoteratozoospermia-affected family. Mfsd6l knock-out male mice also present male subfertility with reduced sperm concentration, motility, and deformed acrosomes. Further mechanistic analyses reveal that MFSD6L, as an acrosome membrane protein, plays an important role in the formation of acrosome by interacting with the inner acrosomal membrane protein SPACA1. Moreover, poor embryonic development is consistently observed after intracytoplasmic sperm injection treatment using spermatozoa from the MFSD6L-deficient man and male mice. Collectively, our findings reveal that MFSD6L is required for the anchoring of sperm acrosome and head shaping. The deficiency of MFSD6L affects male fertility and causes oligoasthenoteratozoospermia in humans and mice.