Molecular Genetic Factors Research Articles

Association of clinical-morphological and molecular-genetic factors (mutations in GNAQ and GNA11 oncogenes and АBСB1 gene polymorphism) in patients with iris melanoma

Association of clinical-morphological and molecular-genetic factors (mutations in GNAQ and GNA11 oncogenes and АBСB1 gene polymorphism) in patients with iris melanoma

Unravelling the genetic landscape of cervical insufficiency: Insights into connective tissue dysfunction and hormonal pathways

Background The intricate molecular pathways and genetic factors that underlie the pathophysiology of cervical insufficiency (CI) remain largely unknown and understudied. Methods We sequenced exomes from 114 patients in Latvia and Lithuania, diagnosed with a short cervix, CI, or a history of CI in previous pregnancies. To probe the well-known link between CI and connective tissue dysfunction, we introduced a connective tissue dysfunction assessment questionnaire, incorporating Beighton and Brighton scores. The phenotypic data obtained from the questionnaire was correlated with the number of rare damaging variants identified in genes associated with connective tissue disorders (in silico NGS panel). SKAT, SKAT-O, and burden tests were performed to identify genes associated with CI without a priori hypotheses. Pathway enrichment analysis was conducted using both targeted and genome-wide approaches. Results No patient could be assigned monogenic connective tissue disorder neither genetically, neither clinically upon clinical geneticist evaluation. Expanding our exploration to a genome-wide perspective, pathway enrichment analysis replicated the significance of extracellular matrix-related pathways as important contributors to CI’s development. A genome-wide burden analysis unveiled a statistically significant prevalence of rare damaging variants in genes and pathways associated with steroids (p-adj = 5.37E-06). Rare damaging variants, absent in controls (internal database, n = 588), in the progesterone receptor (PGR) (six patients) and glucocorticoid receptor (NR3C1) (two patients) genes were identified within key functional domains, potentially disrupting the receptors’ affinity for DNA or ligands. Conclusion Cervical insufficiency in non-syndromic patients is not attributed to a single connective tissue gene variant in a Mendelian fashion but rather to the cumulative effect of multiple inherited gene variants highlighting the significance of the connective tissue pathway in the multifactorial nature of CI. PGR or NR3C1 variants may contribute to the pathophysiology of CI and/or preterm birth through the impaired progesterone action pathways, opening new perspectives for targeted interventions and enhanced clinical management strategies of this condition.

Role of molecular genetic factors in formation of the clinical type of neurofibromatosis type 2

Neurofibromatosis type 2 is a hereditary disease with predisposition to the development of multiple tumors of the central and peripheral nervous system. The disease is characterized by significant variability in the clinical picture; the number of neoplasms, their location and growth rate largely determine the severity of the course. However, assessing the rate of tumor growth requires the availability of a consistent series of instrumental studies conducted within a certain time range, which is not always available at the time of initial treatment. In this study, based on quantitative (age of onset, age of examination) and qualitative (large number of intracranial tumors, large number of spinal tumors, severity of neurological symptoms, mosaic status of the genetic variant) characteristics, an alternative classification of clinical subtypes of neurofibromatosis type 2 was developed. We have revealed statistically significant differences (p-value = 0.037) in the representation of Halliday prognostic classes between the groups identified using the proposed classification which allows us to suggest the possibility of integrating this approach into clinical practice.

Integrative Bioinformatics Approaches to Uncover Hub Genes and Pathways Involved in Cardiovascular Diseases.

Cardiovascular diseases (CVD) represent a significant global health challenge resulting from a complex interplay of genetic, environmental, and lifestyle factors. However, the molecular pathways and genetic factors involved in the onset and progression of CVDs remain incompletely understood. Here, we performed an integrative bioinformatic analysis to highlight specific genes and signaling pathways implicated in the pathogenesis of 80 CVDs. Differentially expressed genes (DEGs) were identified through the integrated analysis of microarray and GWAS datasets. Then, hub genes were identified after gene ontology functional annotation analysis and protein-protein internet (PPI) analysis. In addition, pathways were identified through KEGG and gene ontology enrichment analyses. A total of 821 hub genes related to 80 CVDs were identified, including 135 common and frequent CVD-associated genes. TNF, IL6, VEGFA, and TGFB.1 genes were the central core genes expressed in 50% or more of CVDs, confirming that the inflammation is a key pathological feature of CVDs. Analysis of hub genes by KEGG enrichment revealed predominant enrichment in 201 KEGG pathways, of which the AGE-RAGE signaling pathway in diabetic complications was identified as the common key KEGG implicated in 62 CVDs. In addition, the outcomes showed an overrepresentation in pathways categorized under human diseases, particularly in the subcategories of infectious diseases and cancers, which may be common risk factors for CVDs. In conclusion, this powerful approach for in silico fine-mapping of genes and pathways allowed the identification of determinant hubs genes and pathways implicated in the pathogenesis of CVDs which could be employed in developing more targeted and effective interventions for preventing, diagnosing, and treating CVDs. The function of these hub genes in CVDs needs further exploration to elucidate their biological characteristics.

ADVANCEMENTS IN UNDERSTANDING THE MOLECULAR MECHANISMS REGULATING URIC ACID METABOLISM IN THE INTESTINE

This review provides contemporary insights into the direct and indirect pathogenetic connections between purine compound metabolism and biochemical processes within the cells of the gastrointestinal system. A thorough analysis of recent publications from 2000 to 2024, sourced from databases including Scopus, PubMed, eLIIBRARY, and Google Scholar, was conducted. Uric acid serves as the end product of purine-containing compound catabolism. Its concentration is intricately regulated through the collaboration of the kidneys and gastrointestinal organs, namely the small intestine and liver. Gout, a chronic condition, emerges from the interplay between molecular genetic factors and external influences. Elevated levels of urates in the blood serum (hyperuricemia) and the deposition of sodium urate crystals in organs and tissues set off a cascade of inflammatory and fibrotic processes within mucosal, smooth muscle, parenchymal, and endothelial cells, including those within the gastrointestinal tract. Normally, a person excretes about 1.5 g of uric acid per day. Under physiological conditions, two-thirds of uric acid is excreted from the body by the kidneys, one-third through the intestines, and a small part is excreted with bile. The hypothesis that links the pathogenesis of hyperuricemia with “renal overload” suggests that the disease may develop as a result of impaired renal excretion with insufficient elimination of uric acid through the intestines. Part of uric acid transport systems actively works in hepatocytes and enterocytes, which determines its formation and clearance. Uric acid transporter proteins are divided into two categories: urate reabsorption transporters and urate excretion transporters, their expression is regulated by transcription factors, hormones and metabolites of intestinal microflora. The influence of intestinal microbiota on uric acid metabolism is related to its participation in purine metabolism, decomposition and elimination of uric acid with metabolites of intestinal flora and inhibition of gouty inflammation and is evaluated as a new therapeutic potential in gout and hyperuricemia, which allows to avoid kidney damage and urolithiasis.

Abstract LB211: Genetic complexity in OSCC metastasis: From transcription factors to novel therapeutic targets

Abstract Background: The survival of patients with oral cavity squamous cell carcinoma (OSCC) is largely influenced by the extent of locoregional recurrence. Recurrence after standard therapy occurs in about 30% of patients with late-stage OSCC, highlighting the challenge in managing this aggressive form of cancer. The transition of cells from an epithelial to mesenchymal phenotype is a critical event in OSCC invasion and metastasis and is governed by a complex interplay of genes and signaling pathways, with transcription factors such as ZEB1/2 and SNAI1/2 being pivotal players in this process. However, these transcription factors have proven challenging to target therapeutically, and it is likely that additional genes play crucial roles in OSCC pathology. Furthermore, the biology of locoregionally aggressive OSCC cancer cells is poorly understood, and this gap in knowledge is critical to predicting patient outcomes and improving treatment. This lack of understanding underscores the need for further research into identifying the specific molecular mechanisms and genetic factors that drive the locoregional aggressiveness of OSCC. Objective: To evaluate the impact of individual genes on OSCC cell migration, perform a comprehensive analysis of gene-specific effects on cell migration, and develop a valuable platform for the discovery of potential therapeutic targets. Methods: Our lab has created an in vitro model system of “mesenchymal-like” OSCC which exhibits increased migration and chemotherapeutic resistance. Using this model, we generated several cell lines expressing either Cas9 or an activating dCas9. We next transfected genome wide sgRNA libraries. Using a transwell assay platform we are working to identify several key genes necessary for successful cell migration and genes that amplify OSCC cell migratory potential. Results: Our results indicate that OSCC invasion and regional metastasis is a multifaceted process influenced by a network of genes beyond the well-known transcription factors. By subdividing gene expression changes based on E-cadherin protein expression, we are working to therapeutically isolate genes that may be critical during the fleeting transition from an epithelial to mesenchymal phenotype necessary for aggressive OSCC biology. Conclusions: We have identified several genes whose knockout or activation resulted in a significant impact on cell migration, shedding light on potential candidates for therapeutic intervention. The findings from this study will open new avenues for the development of targeted therapies to improve the prognosis of OSCC patients by focusing on previously unexplored genes involved in the invasion and metastatic cascade. Citation Format: Guillermo Flores, Slyn Uaroon, Marisa Buchakjian. Genetic complexity in OSCC metastasis: From transcription factors to novel therapeutic targets [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB211.

Progression-free survival after first recurrence in patients with glioblastoma.

Relevance. Despite all the treatment glioblastoma recurs as an aggressive and therapy-resistant tumor, and patients quickly die from these neoplasms. The study of glioblastoma recurrence processes and search for prognostic factors of the disease should lead to the improvement of survival rates of patients with this pathology. Purpose of the study. To study the influence of clinical and molecular-genetic factors on the median second recurrence-free period. Materials and methods. Progression-free survival after first recurrence in 34 patients aged 28 to 81 years with recurrent glioblastoma was analyzed. The diagnosis was established according to the WHO 2021 classification of CNS tumors. In each observation we studied such clinical parameters as patient’s age, functional status according to the Karnovsky scale pre- and postoperatively, peculiarities of neuroimaging picture (prevalence of tumor process, localization of recurrence, tumor volume), conducted treatment and molecular-genetic characteristics of the tumor (determination of mRNA expression level of genes: MGMT, VEGF, PDGFRA, β-tubulin III, ERCC-1, TOP2A). Results. Among the clinical and demographic characteristics, the median of the survival was influenced by the patients’ age and functional status after surgery. The median of the survival was more than 2 times higher in the group of patients under 50 years old, compared to patients over 50 years old (18.5 vs 8 weeks). The dependence of the median of the survival on the post- operative functional status (according to the Karnovsky scale) was determined (p = 0.001). The median of the survival in case of a single brain lobe lesion was more than 5 times higher than in case of widespread tumor process, though without statistical reliability (p = 0.09, 21.5 vs 4 weeks). Survival rates were higher when recurrence was localized within 2 cm of the area of removal of the primary neoplasm. After disease progression, the MGMT gene lost its predictive value. Patients with low expression of the TOR2A gene had a higher survival rate than those with medium and high expression (47.5 vs 3 weeks, p = 0.001; 47.5 vs 22.5 weeks, p = 0.06). The median of survival was higher than at high levels at low and medium PDGFRA gene expression levels (29 vs 0 weeks, p = 0.04; 21 vs 0 weeks; p = 0.05, respectively). Maximum survival rates were recorded in the group of patients after total and subtotal removal of tumor recurrence (22 and 18.5 weeks, p = 0.05). Administration of second-line chemotherapy with temozolomide statistically significantly increased the median of the second BRS (p = 0.01). Conclusion. Recurrent glioblastomas are characterized by an extremely aggressive course. Therefore, such prognostic factors as patient age, degree of tumor resection, tumor process prevalence, degree of tumor resection and 2nd line chemotherapy come to the forefront. It should be noted that the MGMT gene loses its predictive value during disease progression, while the TOR2A gene and PDGFRA gene become prognostic markers.

Uveal melanoma: the value of molecular genetic testing for early detection of metastatic disease. Clinical case

To date, the issue of not only timely diagnosis and treatment of patients with uveal melanoma (UM), but also the prediction of this pathology remains relevant. The technology of fine needle aspiration biopsy (FNAB) makes it possible to assess the risk of developing metastatic disease using tumor specimen in patients undergoing organ-preserving treatment by cytological and molecular genetic testing in the primary intraocular lesion. Here we present a case of newly identified locally advanced (T3a) UM, outline the possibilities of organ-preserving treatment using Gamma Knife stereotactic radiosurgery, and also demonstrate the feasibility of conducting a comprehensive prognostic testing on FNAB material, including cytological and molecular genetic and morphological prognostic factors. The results of this testing have made it possible to recommend a more frequent surveillance monitoring regime for metastatic disease, which ultimately led to the early detection of UM liver metastases, followed by their successful treatment.

Cohort profile: BioMD-Y (biopsychosocial factors of major depression in youth) – a biobank study on the molecular genetics and environmental factors of depression in children and adolescents in Munich

PurposeBioMD-Y is a comprehensive biobank study of children and adolescents with major depression (MD) and their healthy peers in Germany, collecting a host of both biological and psychosocial information from...

Metabolomics unveils the exacerbating role of arachidonic acid metabolism in atherosclerosis.

Atherosclerosis is a complex vascular disorder characterized by the deposition of lipids, inflammatory cascades, and plaque formation in arterial walls. A thorough understanding of its causes and progression is necessary to develop effective diagnostic and therapeutic strategies. Recent breakthroughs in metabolomics have provided valuable insights into the molecular mechanisms and genetic factors involved in atherosclerosis, leading to innovative approaches for preventing and treating the disease. In our study, we analyzed clinical serum samples from both atherosclerosis patients and animal models using laser desorption ionization mass spectrometry. By employing methods such as orthogonal partial least-squares discrimination analysis (OPLS-DA), heatmaps, and volcano plots, we can accurately classify atherosclerosis (AUC = 0.892) and identify key molecules associated with the disease. Specifically, we observed elevated levels of arachidonic acid and its metabolite, leukotriene B4, in atherosclerosis. By inhibiting arachidonic acid and monitoring its downstream metabolites, we discovered the crucial role of this metabolic pathway in regulating atherosclerosis. Metabolomic research provides detailed insights into the metabolic networks involved in atherosclerosis development and reveals the close connection between abnormal metabolism and the disease. These studies offer new possibilities for precise diagnosis, treatment, and monitoring of disease progression, as well as evaluating the effectiveness of therapeutic interventions.

Role of Molecular Genetic Factors in Formation of the Clinical Type of Neurofibromatosis Type 2

Role of Molecular Genetic Factors in Formation of the Clinical Type of Neurofibromatosis Type 2

Molecular mechanisms and genetic factors contributing to the developmental dysplasia of the hip.

The most prevalent hip disease in neonates is developmental dysplasia of the hip (DDH). A timely and accurate diagnosis is required to provide the most effective treatment for pediatric patients with DDH. Heredity and gene variation have been the subject of increased attention and research worldwide as one of the factors contributing to the pathogenesis of DDH. Genome-wide association studies (GWAS), genome-wide linkage analyses (GWLA), and exome sequencing (ES) have identified variants in numerous genes and single-nucleotide polymorphisms (SNPs) as being associated with susceptibility to DDH in sporadic and DDH family patients. Furthermore, the DDH phenotype can be observed in animal models that exhibit susceptibility genes or loci, including variants in CX3CR1, KANSL1, and GDF5. The dentification of noncoding RNAs and de novo gene variants in patients with DDH-related syndrome has enhanced our understanding of the genes implicated in DDH. This article reviews the most recent molecular mechanisms and genetic factors that contribute to DDH.

Patients with long-term survival in malignant gliomas after photodynamic therapy

Analysis of long-lived patients from the group of patients with glioblastomas after using photodynamic therapy in the structure of their complex treatment in order to assess the influence of various factors on their life expectancy. In total, a single-center, retrospective categorical study analyzed the long-term results of treatment of 63 patients with glioblastoma in the structure of complex treatment including photodynamic therapy. Clinical factors (age, sex, number of cases, preoperative Karnofsky index, location and size of the tumor, radicality of the operation), histological (nuclear polymorphism, mitosis, vascular proliferation, necrosis), immunohistochemical (Ki-67, p53 index) molecular-genetic factors (expression of VEGF, MGMT, IDH, CD34), amount of radiation and chemotherapy were analyzed. In the entire group of patients, there was a direct correlation of life expectancy with MGMT status, IDH status, the number of courses of chemotherapy, the age of the patient, and the severity of the first surgical intervention. Clinical features such as age at diagnosis and extent of surgical resection and amount of chemotherapy have predictive value in assessing their effect on life expectancy. Mutations in IDH and MGMT promoter methylation were the most important molecular factors determining long-term patient survival.

An FGFR2 mutation as the potential cause of a new phenotype including early-onset osteoporosis and bone fractures: a case report

Osteoporosis is a systemic, multifactorial disorder of bone mineralization. Many factors contributing to the development of osteoporosis have been identified so far, including gender, age, nutrition, lifestyle, exercise, drug use, as well as a range of comorbidities. In addition to environmental and lifestyle factors, molecular genetic factors account for 50–85% of osteoporosis cases. For example, the vitamin D receptor (VDR), collagen type I (COL1), estrogen receptor (ER), apolypoprotein Е (ApoE), bone morphogenetic protein (BMP), and Low-density lipoprotein receptor-related protein 5 (LRP5) are all involved in the pathogenesis of osteoporosis. Among the candidate genes, the pathogenic variants in which are involved in the pathogenesis of osteoporosis is FGFR2. Additionally, FGFs/FGFRs-dependent signaling has been shown to regulate skeletal development and has been linked to a plethora of heritable disorders of the musculoskeletal system. In this study we present the clinical, biochemical and radiological findings, as well as results of molecular genetic testing of a 13-year-old male proband with heritable osteoporosis, arthralgia and multiple fractures and a family history of abnormal bone mineralization and fractures. Whole exome sequencing found a heterozygous previously undescribed variant in the FGFR2 gene (NM_000141.5) (GRCh37.p13 ENSG00000066468.16: g.123298133dup; ENST00000358487.5:c.722dup; ENSP00000351276.5:p.Asn241LysfsTer43). The same variant was found in two affected relatives. These data lead us to believe that the variant in FGFR2 found in our proband and his relatives could be related to their phenotype. Therefore, modern methods of molecular genetic testing can allow us to differentiate between osteogenesis imperfecta and other bone mineralization disorders.

Molecular genetic abnormalities in ACTH-secreting pituitary tumors (corticotropinomas): fundamental research and prospects for use in clinical practice

In recent years, a large number of studies have been carried out to research molecular genetic abnormalities in ACTH--secreting pituitary tumors. This review presents a comprehensive analysis of exome studies results (germline and somatic mutations, chromosomal abnormalities in corticotropinomas which developed as part of hereditary syndromesMEN 1, 2, 4, DICER1, Carney complex etc., and isolated tumors, respectively) and transcriptome (specific genes expression profiles in hormonally active and inactive corticotropinomas, regulation of cell cycles and signal pathways). Modern technologies (next-generation sequencing - NGS) allow us to study the state of the microRNAome, DNA methylome andinactive chromatin sites, in particular using RNA sequencing. Thus, a wide range of fundamental studies is shown, theresults of which allow us to identify and comprehend the key previously known and new pathogenesis mechanisms andbiomarkers of corticotropinomas. The characteristics of the most promising molecular genetic factors that can be used in clinical practice for screening and earlier diagnosis of hereditary syndromes and isolated corticotropinomas, differential diagnosis of various forms of endogenous hypercorticism, sensitivity to existing and potential therapies andpersonalized outcome determination of Cushing`s disease.

Monooxygenases and Antibiotic Resistance: A Focus on Carbapenems.

Carbapenems are a group of broad-spectrum beta-lactam antibiotics that in many cases are the last effective defense against infections caused by multidrug-resistant bacteria, such as some strains of Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. Resistance to carbapenems has emerged and is beginning to spread, becoming an ongoing public-health problem of global dimensions, causing serious outbreaks, and dramatically limiting treatment options. This paper reviews the role of flavin monooxygenases in antibiotic resistance, with a specific focus on carbapenem resistance and the recently discovered mechanism mediated by Baeyer-Villiger monooxygenases. Flavin monooxygenases are enzymes involved in the metabolism and detoxification of compounds, including antibiotics. Understanding their role in antibiotic resistance is crucial. Carbapenems are powerful antibiotics used to treat severe infections caused by multidrug-resistant bacteria. However, the rise of carbapenem-resistant strains poses a significant challenge. This paper explores the mechanisms by which flavin monooxygenases confer resistance to carbapenems, examining molecular pathways and genetic factors. Additionally, this paper highlights the discovery of Baeyer-Villiger monooxygenases' involvement in antibiotic resistance. These enzymes catalyze the insertion of oxygen atoms into specific chemical bonds. Recent studies have revealed their unexpected role in promoting carbapenem resistance. Through a comprehensive analysis of the literature, this paper contributes to the understanding of the interplay between flavin monooxygenases, carbapenem resistance, and Baeyer-Villiger monooxygenases. By exploring these mechanisms, it aims to inform the development of strategies to combat antibiotic resistance, a critical global health concern.

Genetic Factors of Reflex Epilepsies

Reflex epilepsy is a relatively rare form of epilepsy, occurring only in five percent of all cases of this disease. The genetic factors of reflex epilepsy are diverse and, in general, poorly studied. This review examines the main results obtained in recent years in the study of molecular genetic factors of reflex epilepsy, including new data on the mechanisms of genetic regulation in reflex epilepsy caused by triggers such as audio and video stimulation, food consumption, reading, contact with water and hypoxia. The results obtained in studies on animal models and patients using next-generation sequencing technology are presented.

Exploring the molecular features and genetic prognostic factors of pulmonary high-grade neuroendocrine carcinomas

Molecular research on large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC) has progressed significantly. However, there are still fewer molecular markers related to prognostic/therapeutic strategies for these conditions compared to those for adenocarcinoma. We therefore investigated the molecular characteristics of neuroendocrine carcinomas (NECs). We enrolled patients surgically diagnosed with NECs between 2011 and 2019, with complete follow-up records. All were analyzed using whole exome sequencing and p53/Rb immunohistochemistry (IHC). A total of 92 cases, comprising 45 pure SCLC, 15 combined SCLC, 27 pure LCNEC, and 5 combined LCNEC, were included. TP53 (78.3%) and RB1 (34.8%) were the most common molecular alterations, followed by KMT2D, LRP1B, FAT3, NCOR2, SPTA1, and NOTCH1. The mutation frequency for EGFR was 10.9%. Sixteen patients with LCNEC who had TP53/RB1 co-alterations were SCLC-like, while the remaining were NSCLC-like. There was no statistically significant difference between the groups regarding overall survival (OS; p=0.458) and progression-free survival (PFS; p=0.157). The frequency of the loss of Rb expression by IHC in SCLC-like LCNEC was 100%. Significant pathway alterations unique to SCLC included Notch and AMPK, while HIF-1 was enriched exclusively in LCNEC. NCOR2 mutation was linked to worse OS (p=0.029) and PFS (p=0.015), while wild-type SPTA1 was associated with poor PFS (p=0.018). IHC for Rb was reliable for predicting LCNEC molecular subtypes, indicating its clinical value. NCOR2 and SPTA1 alterations were identified as prognostic factors that may provide therapeutic targets for patients with NEC.

Molecular genetic traits and risk factors for neuroblastoma

Neuroblastoma is the most common extracranial solid tumor in childhood, accounting for 815% of all malignant neoplasms in children. The uniqueness of the neuroblastoma etiology and pathogenesis creates significant difficulties for doctors due to the unpredictability of the course of the disease: the tumor can regress and lead to death in a short time, showing significant immunity to ongoing therapy. Early diagnosis of a tumor is necessary to understand the risk factors, the etiology, the mechanisms of neuroblastoma occurrence and further development. To date, a number of different risk factors have been identified, related both to genetic aspects and to aspects related to the course of pregnancy, birth and lifestyle of the childs parents. The list of these risk factors is still incomplete and research to identify new factors continues to this day. Morphological and molecular genetic diagnostics play an important role in this. Undifferentiated and low-differentiated variants of neuroblastoma are often associated with MYCN amplification and other chromosomal aberrations determined by molecular genetic research. Chromosomal instability plays an important role in the process of early tumor development, which probably causes the possibility of acquiring certain genetic changes, which also determines the prognosis and further therapeutic options. In this article, we have identified the most significant risk factors by comparing the results of various studies.

Molecular Regulation of Bud Regeneration from Callus of Hybrid Sweetgum (Liquidambar styraciflua × Liquidambar formosana)

Adventitious bud regeneration is an effective means of rapid propagation of plants, which can be used in the study of plant development and genetic transformation. It can be divided into direct and indirect adventitious bud regeneration. Of the two kinds of adventitious bud regeneration mentioned, indirect adventitious bud regeneration includes callus formation in vitro and organ regeneration. In the process of callus formation, some cells acquire the pluripotency of tissue regeneration, which is the key to regeneration of adventient buds. It is not clear which molecular processes and genetic factors are involved in establishing cellular pluripotency. The object of the study is hybrid sweetgum (Liquidambar styraciflflua × L. formosana). At present, the reproductive efficiency of hybrid sweetgum is low and the reproductive cycle is long. Improving its reproductive efficiency by improving the differentiation speed of callus may be a decent approach. In order to explore the mechanism of pluripotency acquisition during forming hybrid sweetgum callus, we used RNA-seq to perform transcriptomic analysis of the regenerable calli (RC) and non-regenerable (NRC) calli of hybrid sweetgum. A dataset of differentially expressed genes (DEG) was obtained and several genes probably involved in bud formation were analyzed to explain the molecular processes of acquiring and maintaining pluripotency. In this study, a total of 665 significantly expressed DEGs were identified in the RC and NRC of hybrid sweetgum, among which, 585 differentially expressed genes were up-regulated and 80 differentially expressed genes were down-regulated. GO, KEGG analysis and qRT-PCR results showed phenylpropanoid is a key factor regulating the bud regeneration of hybrid sweetgum; WOX1, WOX11, BGLU12 and BGLU13 were also important regulatory factors. These results provide a pivotal reference point for future sweetgum propagation research.