SoyMD: a platform combining multi-omics data with various tools for soybean research and breeding.

Advanced multi-omics technologies offer much information that can uncover the regulatory mechanisms from genotype to phenotype. In soybean, numerous multi-omics databases have been published. Although they cover multiple omics, there are still limitations when it comes to the types and scales of omics datasets and analysis methods utilized. This study aims to address these limitations by collecting and integrating a comprehensive set of multi-omics datasets. This includes 38 genomes, transcriptomes from 435 tissue samples, 125 phenotypes from 6686 accessions, epigenome data involving histone modification, transcription factor binding, chromosomal accessibility and chromosomal interaction, as well as genetic variation data from 24 501 soybean accessions. Then, common analysis pipelines and statistical methods were applied to mine information from these multi-omics datasets, resulting in the successful establishment of a user-friendly multi-omics database called SoyMD (https://yanglab.hzau.edu.cn/SoyMD/#/). SoyMD provides researchers with efficient query options and analysis tools, allowing them to swiftly access relevant omics information and conduct comprehensive multi-omics data analyses. Another notable feature of SoyMD is its capability to facilitate the analysis of candidate genes, as demonstrated in the case study on seed oil content. This highlights the immense potential of SoyMD in soybean genetic breeding and functional genomics research.

Genome-wide identification and functional prediction of BYPASS1-related (BPS1) homologs in soybean.

The BYPASS1-related gene (BPS1) encodes a protein with an unknown functional domain that regulates plant organ growth and development by inhibiting the continuous production of a root-derived long-distance signaling molecule called bypass (bps). We conducted a comprehensive study to investigate the BPS gene family in soybean and identified twenty-three BPS genes in Glycine max and twenty BPS genes in Glycine soja (wild soybean). Collinearity analysis revealied the existence of multiple orthologs of soybean BPS genes in wild soybean, indicating incomplete conservation between the BPS genes of soybean and wild soybean. Phylogenetic analysis successfully categorized all BPS genes into five distinct groups. We further scrutinized their chromosomal locations, gene structures, conserved motifs, cis-acting elements, and expression patterns. Leveraging publicly available data on genetic variation, phenotypic variation, and single-cell transcriptome sequencing of root nodules, we discovered a potential association between BPS genes and multiple soybean traits, particularly those related to the root nodule phenotype. This pioneering study provides a systematic and comprehensive examination of the BPS gene family in soybean. The findings establish a robust foundation for future investigations into the functional roles of BPS genes in plant growth and development. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01403-2.

Genome-wide analysis of the serine carboxypeptidase-like protein family reveals Ga09G1039 is involved in fiber elongation in cotton.

The Gossypium is a model genus for understanding polyploidy and the evolutionary pattern of inheritance. This study aimed to investigate the characteristics of SCPLs in different cotton species and their role in fiber development. A total of 891 genes from one typical monocot and ten dicot species were naturally divided into three classes based on phylogenetic analysis. The SCPL gene family in cotton has undergone intense purifying selection with some functional variation. Segmental duplication and whole genome duplication were shown to be the two main reasons for the increase in the number of genes during cotton evolution. The identification of Gh_SCPL genes exhibiting differential expression in particular tissues or response to environmental stimuli provides a new measure for the in-depth characterization of selected genes of importance. Ga09G1039 was involved in the developmental process of fibers and ovules, and it is significantly different from proteins from other cotton species in terms of phylogenetic, gene structure, conserved protein motifs and tertiary structure. Overexpression of Ga09G1039 significantly increased the length of stem trichomes. Ga09G1039 may be a serine carboxypeptidase protein with hydrolase activity, according to functional region, prokaryotic expression, and western blotting analysis. The results provide a comprehensive overview of the genetic basis of SCPLs in Gossypium and further our knowledge in understanding the key aspects of SCPLs in cotton with their potential role in fiber development and stress resistance.

Divergence of functions and expression patterns of soybean bZIP transcription factors.

Soybean (Glycine max) is a major protein and oil crop. Soybean basic region/leucine zipper (bZIP) transcription factors are involved in many regulatory pathways, including yield, stress responses, environmental signaling, and carbon-nitrogen balance. Here, we discuss the members of the soybean bZIP family and their classification: 161 members have been identified and clustered into 13 groups. Our review of the transcriptional regulation and functions of soybean bZIP members provides important information for future study of bZIP transcription factors and genetic resources for soybean breeding.

The genetic basis of high-latitude adaptation in wild soybean.

In many plants, flowering time is influenced by daylength as an adaptive response. In soybean (Glycine max) cultivars, however, photoperiodic flowering reduces crop yield and quality in high-latitude regions. Understanding the genetic basis of wild soybean (Glycine soja) adaptation to high latitudes could aid breeding of improved cultivars. Here, we identify the Tof4 (Time of flowering 4) locus, which encodes by an E1-like protein, E1La, that represses flowering and enhances adaptation to high latitudes in wild soybean. Moreover, we found that Tof4 physically associates with the promoters of two important FLOWERING LOCUS T (FT2a and FT5a) and with Tof5 to inhibit their transcription under long photoperiods. The effect of Tof4 on flowering and maturity is mediated by FT2a and FT5a proteins. Intriguingly, Tof4 and the key flowering repressor E1 independently but additively regulate flowering time, maturity, and grain yield in soybean. We determined that weak alleles of Tof4 have undergone natural selection, facilitating adaptation to high latitudes in wild soybean. Notably, over 71.5% of wild soybean accessions harbor the mutated alleles of Tof4 or a previously reported gain-of-function allele Tof5H2, suggesting that these two loci are the genetic basis of wild soybean adaptation to high latitudes. Almost no cultivated soybean carries the mutated tof4 allele. Introgression of the tof4-1 and Tof5H2 alleles into modern soybean or editing E1 family genes thus represents promising avenues to obtain early-maturity soybean, thereby improving productivity in high latitudes.

Sheep tail fat inhibits the proliferation of non-small-cell lung cancer cells in vitro and in vivo.

Increasing evidence suggests that numerous edible oils may function as adjuvant dietary therapies to treat cancer. We previously reported that the odd-chain saturated fatty acid (OCSFA), heptadecanoic acid (C17:0), profoundly inhibits non-small-cell lung cancer (NSCLC) cell proliferation. However, the antitumor potential of edible lipids rich in C17:0 remains unclear. Here, we determined that sheep tail fat (STF) is a dietary lipid rich in C17:0 and exhibited the greatest inhibitory effect against three NSCLC cell lines (A549, PC-9, and PC-9/GR) among common dietary lipids. Cell migration experiments demonstrated that STF could significantly inhibit the wound healing capacity of three NSCLC cell lines by promoting the generation of reactive oxygen species (ROS) and subsequent cell death. Mechanistic studies showed that STF suppressed NSCLC cell growth by downregulating the Akt/S6K signaling pathway. Furthermore, administration of STF reduced tumor growth, weight, and expression of the proliferative marker Ki-67 in nude mice bearing A549 xenografts. Collectively, our data show that STF has antitumor activity against NSCLC, implying that dietary intake of C17:0-rich STF may be a potential adjuvant therapy for NSCLC.

GhGASA10-1 promotes the cell elongation in fiber development through the phytohormones IAA-induced.

BACKGROUND: Cotton is an important cash crop. The fiber length has always been a hot spot, but multi-factor control of fiber quality makes it complex to understand its genetic basis. Previous reports suggested that OsGASR9 promotes germination, width, and thickness by GAs in rice, while the overexpression of AtGASA10 leads to reduced silique length, which is likely to reduce cell wall expansion. Therefore, this study aimed to explore the function of GhGASA10 in cotton fibers development. RESULTS: To explore the molecular mechanisms underlying fiber elongation regulation concerning GhGASA10-1, we revealed an evolutionary basis, gene structure, and expression. Our results emphasized the conservative nature of GASA family with its origin in lower fern plants S. moellendorffii. GhGASA10-1 was localized in the cell membrane, which may synthesize and transport secreted proteins to the cell wall. Besides, GhGASA10-1 promoted seedling germination and root extension in transgenic Arabidopsis, indicating that GhGASA10-1 promotes cell elongation. Interestingly, GhGASA10-1 was upregulated by IAA at fiber elongation stages. CONCLUSION: We propose that GhGASA10-1 may promote fiber elongation by regulating the synthesis of cellulose induced by IAA, to lay the foundation for future research on the regulation networks of GASA10-1 in cotton fiber development.

An Anti-EGFR/anti- HER2 Bispecific Antibody with Enhanced Antitumor Activity Against Acquired Gefitinib-Resistant NSCLC Cells.

BACKGROUND: Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is a recurrent phenomenon during clinical therapy of non-small-cell lung cancer (NSCLC). Studies have shown that HER2 is a key factor contributing to drug resistance in a variety of cancers. Furthermore, we have observed that HER2 is overexpressed in PC-9 NSCLC cells with acquired gefitinib-resistance (PC-9/GR) as compared to that in PC-9 cells. OBJECTIVE: We hypothesized that blocking both EGFR and HER2 may serve as a potential strategy for the treatment of NSCLC with acquired gefitinib-resistance. METHODS: To target both EGFR and HER2 simultaneously, we developed a bispecific antibody HECrossMAb, which was derived from a humanized Cetuximab and Trastuzumab. The binding affinity of HECrossMAb for EGFR and HER2 was measured using an enzyme-linked immunosorbent assay. The MTT assay was used to determine the effect of HECrossMAb on the proliferation of PC-9 and PC-9/GR cells in vitro. Finally, the effect of HECrossMAb on PI3K/AKT signaling and associated transcription factors was measured using western blot analysis. RESULTS: Our results showed that HECrossMAb exerts enhanced cytotoxicity in both PC-9 and PC-9/GR cells by inhibiting the activation of PI3K/AKT signaling and expression of relevant transcription factors such as AEG-1, c-Myc, and c-Fos. CONCLUSION: Our results suggest that HECrossMAb may function as a potential therapeutic agent for treating NSCLC overexpressing EGFR and HER2.

Stable overexpression of mutated PTEN in Chinese hamster ovary cells enhances their performance and therapeutic antibody production.

Chinese hamster ovary (CHO) cells with a high viable cell density (VCD), resilience to culture stress, and the capacity to continuously express recombinant proteins are highly desirable. Phosphatase and tension homology deleted on chromosome ten (PTEN) functions as a key negative regulator of the PI3K/Akt signaling pathway, mediating cell growth and survival. Its oncogenic mutant endows cells with an enhanced proliferation rate and resistance to death. In this study, the role of oncogenic PTEN C124S or G129E on the performance of CHO-K1 and CHO-IgG cells was investigated. Our results showed that CHO-K1 cells stably expressing PTEN C124S or G129E exhibited enhanced proliferation, reduced apoptosis rate, and increased transient expression of therapeutic antibodies compared to the control cells. Moreover, the stable overexpression of PTEN C124S or G129E endowed CHO-IgG cells with higher cell viability, VCD, and antibody titers (yield increased by approximately 0.77-fold) in the fed-batch culture process and enhanced their performance in response to the addition of sodium lactate. Moreover, the engineering of mutated PTEN in CHO-IgG cells did not alter antibody quality. Collectively, our data suggest that mutated PTEN is a potential target for improving the manufacture of therapeutic antibodies.

Identification and functional analysis of 9-cis-epoxy carotenoid dioxygenase (NCED) homologs in G. hirsutum.

9-cis-epoxy carotenoid dioxygenase (NCED) is a fundamental enzyme, which plays an essential role in the process of organ development and stress resistance by regulating abscisic acid (ABA) synthesis in plant. In this study, a total of 7, 7, 14 and 14 NCED genes were identified from the genomes of G. arboreum, G. raimondii, G. barbadense and G. hirsutum, respectively. Phylogenetic tree showed that all forty-two NCED genes could be classified into three groups in cotton genus. Collinear analysis revealed that the NCED genes in G. hirsutum were not amplified by tandem repeats after polyploidy events. The function of NCED genes was evaluated between two accessions with contrasting plant height. The results showed that expression of the NCED genes in dwarf accession was higher than that in taller ones. GhNCED1-silenced cotton plants confirmed that suppression of NCED genes could increase the plant height, but reduce the resistance abilities to drought and salt stress. Our study systematically identified the homologs of NCED genes and their functions in cotton, which could provide new genetic resources for improving plant height and stress in future cotton breeding.

A copy number variant at the HPDA-D12 locus confers compact plant architecture in cotton.

Improving yield is a primary mission for cotton (Gossypium hirsutum) breeders; development of cultivars with suitable architecture for high planting density (HPDA) can increase yield per unit area. We characterized a natural cotton mutant, AiSheng98 (AS98), which exhibits shorter height, shorter branch length, and more acute branch angle than wild-type. A copy number variant at the HPDA locus on Chromosome D12 (HPDA-D12), encoding a dehydration-responsive element-binding (DREB) transcription factor, GhDREB1B, strongly affects plant architecture in the AS98 mutant. We found an association between a tandem duplication of a c. 13.5 kb segment in HPDA-D12 and elevated GhDREB1B expression resulting in the AS98 mutant phenotype. GhDREB1B overexpression confers a significant decrease in plant height and branch length, and reduced branch angle. Our results suggest that fine-tuning GhDREB1B expression may be a viable engineering strategy for modification of plant architecture favorable to high planting density in cotton.