Biology subjects

Xu, F.

Publications and source records attributed to Xu, F..

At least 127 records · Page 7Linked to original sources

bioRxiv2022

Wounding promotes root regeneration through a cell wall integrity sensor, the receptor kinase FERONIA

Wounding caused by various stresses is the initial event of plant regeneration. However, the mechanisms underlying the early wounding responses to promote plant regeneration remain largely unknown. Here, we report that the receptor kinase FERONIA (FER) interacts with Topless/Topless-related proteins (TPL/TPRs) to regulate the expression of regeneration-related genes to modulate root tip regeneration. One ligand of FER, rapid alkalinization factor 33 (RALF33), is stimulated by wounding and functions together with FER to promote regeneration. Single-cell sequencing data showed that the low-differentiation cell types in the stele may account for the enhanced regeneration ability in the fer mutant, especially in the columella and quiescent center (QC). Further interaction assays and analysis of the gene expression patterns in low-differentiation cell types confirmed that FER interacts with TPL/TPRs to regulate the expression of downstream regeneration-related genes. One of their downstream targets, an essential transcription factor (TF) in root regeneration, ERF115, acts downstream of FER-TPL/TPRs to control regeneration. Our results suggested a signaling pathway between the early wounding response and regeneration processes in roots. One-sentence summaryRALF33-FER serves as an early signaling module between wounding and regeneration by functioning with TPL/TPRs in roots.

cell biology↗

bioRxiv2022

Novel methods to identify TCM constitution of hyperlipidemic patients and predict atherosclerotic diseases

Hyperlipidemia can accelerate the progression of atherosclerosis, ultimately leading to cardiovascular disease. TCM constitution has been widely used as an indicator of health status and susceptibility to diseases. However, there still lack of objective, credible ways to identify TCM constitution of hyperlipidemic patients, and the connection between TCM constitution and atherosclerotic diseases in individuals with hyperlipidemia is unknown. This study aims to identify differentially expressed microRNAs (DEMs) as biomarkers of the TCM constitution of hyperlipidemic patients and explore the potential connection between TCM constitution and atherosclerotic diseases. In the study, we randomly recruited 10 hyperlipidemic patients with asthenic constitution (HAC), 10 hyperlipidemic patients with strong constitution (HSC), and 10 hyperlipidemic patients with normal constitution (HNC) and collected serum miRNA. After analyzing the miRNA expression profiles, we found that hsa-miR-338-3p may be a potential blood biomarker for the identification of the TCM constitution of hyperlipidemic patients. Moreover, the HSC classification is likely a cardiocerebrovascular disease predisposition and is closely related to the inflammatory process and glucose and lipid metabolism, which contribute to the development of atherosclerotic diseases.

bioinformatics↗

bioRxiv2022

TLR4/NF-κB Signaling Contributes to the Inflammation in Ovary and Inguinal Fats of Polycystic Ovary Syndrome

BackgroundPolycystic ovary syndrome (PCOS) is a complex reproductive endocrine disorder. It has highly heterogeneous clinical manifestations which are characterized by biochemical hyperandrogenemia, obesity, insulin resistance, dyslipidemia, anovulation, and polycystic ovaries. However, the etiologies of PCOS are still unclear. Recently, studies have found that the low-grade inflammation contributed to the occurrence of PCOS, and as a critical biomarker indicated the endocrine disruptions in PCOS. ObjectiveThis study is aimed to investigate the processes and mediators of inflammation in contributing to the development of PCOS. MethodsLetrozole (LET) induced PCOS rat model was used in this study. Body weight, body temperature, inguinal fats weight, fasting glucose level, ovarian morphology, NF-{kappa}B signaling target genes in ovary, and protein expression levels of TLR4 and NF-{kappa}B in ovarian and inguinal fats were measured in rats with placebo and LET administrations for 6 and 12 weeks. ResultsPCOS rats, especially with LET intervention for 12 weeks, had higher body weight, inguinal fats weight and fasting glucose level compared to control group. The protein expression levels of TLR4 and NF-{kappa}B in cytoplasm of ovarian and inguinal fats were increased in LET-induced PCOS rats compared to control groups, while NF-{kappa}B in nucleus were reduced in PCOS rats. The expressions of ACTB, C3, CXCL3, NQO1 and SELP in ovarian were statistically different in PCOS rats induced by LET compared to control groups. ConclusionThese findings indicated that stimulating TLR4/NF-{kappa}B pathway in inguinal fats and ovary tissues contributed to the increased inflammation in LET-induced PCOS rats, which, in turn, exacerbated the phenotype of PCOS including weight gain, adipose tissue accumulation, hyperglycemia and follicular dysplasia.

pathology↗

bioRxiv2022

Phytochromes mediate germination inhibition under red, far-red, and white light in Aethionema arabicum

The view on the role of light during seed germination stems mainly from studies with Arabidopsis, where light is required to initiate this process. In contrast, white light is a strong inhibitor of germination in other plants, exemplified by accessions of Aethionema arabicum, another Brassicaceae. Their seeds respond to light with gene expression changes of key regulators converse to Arabidopsis, resulting in antipodal hormone regulation and prevention of germination. The photoreceptors involved in this process in A. arabicum were unknown. Screening the first mutant collection of A. arabicum, we identified koy-1, a mutant that lost light inhibition of germination, due to a deletion in the promoter of HEME OXYGENASE 1, the gene for a key enzyme in the biosynthesis of the phytochrome chromophore. koy-1 seeds are unresponsive to red- and far-red light and hyposensitive under white light. Comparison of hormone and gene expression between wild type and koy- 1 revealed that very low light fluence stimulates germination, while high irradiance of red and far-red light is inhibitory, indicating a dual role of phytochromes in light-regulated seed germination. The mutation also affects the ratio between the two fruit morphs of A. arabicum, suggesting that light reception via phytochromes can fine-tune several parameters of propagation in adaptation to conditions in the habitat. One sentence summaryCharacterization of a phytochrome chromophore biosynthesis mutant demonstrates an active role of phytochromes in the light-inhibited seed germination in Aethionema arabicum.

plant biology↗

bioRxiv2022

Using NAMs to characterize chemical bioactivity at the transcriptomic, proteomic and phosphoproteomic levels

Omic-based technologies are of particular interest and importance for non-animal chemical hazard and risk characterization based on the premise that any apical endpoint change must be underpinned by some alterations measured at the omic levels. In this work we studied cellular responses to caffeine and coumarin by generating and integrating multi-omic data from transcriptomic, proteomic and phosphoproteomic experiments. We have shown that the methodology presented here is able to capture the complete chain of events from the first compound-induced changes at the phosphoproteome level to changes in gene expression induced by transcription factors and lastly to changes in protein abundance that further influence changes at the cellular level. In HepG2 cells we found the metabolism of lipids and general cellular stress to be dominant biological processes in response to caffeine and coumarin exposure, respectively. The phosphoproteomic changes were detected early in time, at very low concentrations and provided a fast adaptive cellular response to chemical exposure. Changes in protein abundance were found much less frequently than the transcriptomic changes and can be used, together with the transcriptomic changes, to facilitate a more complete understanding of pathway responses to chemical exposure. GRAPHIC ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=169 SRC="FIGDIR/small/492410v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@1e348c8org.highwire.dtl.DTLVardef@bf50c5org.highwire.dtl.DTLVardef@4fea36org.highwire.dtl.DTLVardef@998cb8_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2022

A Self-Healing, Viscoelastic Hydrogel Promotes Healing of Brain Lesions

Brain lesions can arise from traumatic brain injury, infection, and craniotomy. Although injectable hydrogels show promise for promoting healing of lesions and health of surrounding tissue, enabling cellular ingrowth and restoring neural tissue continue to be challenging. We hypothesized that these challenges arise in part from viscoelastic mismatch between the hydrogel and the brain parenchyma, and tested this hypothesis by developing and evaluating a self-healing hydrogel that mimicked both the composition and viscoelasticity of native brain parenchyma. The hydrogel was crosslinked by dynamic boronate ester bonds between phenylboronic acid grafted hyaluronic acid (HA-PBA) and dopamine grafted gelatin (Gel-Dopa). This HA-PBA/Gel-Dopa hydrogel could be injected into a lesion cavity in a shear-thinning manner with rapid hemostasis, high tissue adhesion and efficient self-healing. We tested this in an in vivo mouse model of brain lesions and found the hydrogel to support neural cell infiltration, decrease astrogliosis and glial scars, and close the lesions. The results suggest a role for viscoelasticity in brain lesion healing, and motivate additional experimentation in larger animals as the technology progresses towards potential application in humans.

bioengineering↗

bioRxiv2022

Subtyping evaluation of Salmonella Enteritidis using SNP and core genome MLST with nanopore reads

Whole genome sequencing (WGS) for public health surveillance and epidemiological investigation of foodborne pathogens predominantly relies on sequencing platforms that generate short reads. Continuous improvement of long-read nanopore sequencing such as Oxford Nanopore Technologies (ONT) presents a potential for leveraging multiple advantages of the technology in public health and food industry settings, including rapid turnaround and onsite applicability in addition to superior read length. However, evaluation, standardization and implementation of the ONT approach to WGS-based, strain-level subtyping is challenging, in part due to its relatively high base-calling error rates and frequent iterations of sequencing chemistry and bioinformatic analytics. Using an established cohort of Salmonella Enteritidis isolates for subtyping evaluation, we assessed the technical readiness of ONT for single nucleotide polymorphism (SNP) analysis and core-genome multilocus sequence typing (cgMLST) of a major foodborne pathogen. By multiplexing three isolates per flow cell, we generated sufficient sequencing depths under seven hours of sequencing for robust subtyping. SNP calls by ONT and Illumina reads were highly concordant despite homopolymer errors in ONT reads (R9.4.1 chemistry). In silico correction of such errors allowed accurate allelic calling for cgMLST and allelic difference measurements to facilitate heuristic detection of outbreak isolates. Our study established a baseline for the continuously evolving nanopore technology as a viable solution to high quality subtyping of Salmonella, delivering comparable subtyping performance when used standalone or together with short-read platforms.

microbiology↗

bioRxiv2022

Maps of high density microsatellites accumulation in human genome

BackgroundMicrosatellites are increasingly realized to have biological significance in human genome and health in past decades, the assembled complete reference sequence of human genome T2T-CHM13 brought great help for a comprehensive study of short tandem repeats in the human genome. ResultsMicrosatellites density landscapes of all 24 chromosomes were built here for the first complete reference sequence of human genome T2T-CHM13. These landscapes showed that short tandem repeats (STRs) are prone to aggregate characteristically to form a large number of STRs density peaks. We classified 8,823 High Microsatellites Density Peaks (HMDPs), 35,257 Middle Microsatellites Density Peaks (MMDPs) and 199, 649 Low Microsatellites Density Peaks (LMDPs) on the 24 chromosomes; and also classified the motif types of every microsatellites density peak. These STRs density aggregation peaks are mainly composing of a single motif, and AT is the most dominant motif, followed by AATGG and CCATT motifs. And 514 genomic regions were characterized by microsatellite density feature in the full T2T-CHM13 genome. ConclusionsThese landscape maps exhibited that microsatellites aggregate in many genomic positions to form a large number of microsatellite density peaks with composing of mainly single motif type in the complete reference genome, indicating that the local microsatellites density varies enormously along the every chromosome of T2T-CHM13.

bioinformatics↗

bioRxiv2022

Biochemical characterization of Pectin Methylesterase Inhibitor 3 from Arabidopsis thaliana

The Arabidopsis thaliana PECTIN METHYLESTERASE INHIBITOR 3 (PMEI3) gene is frequently used as a tool to manipulate PME activity in vivo, in studies assessing the role of pectin de-methylesterification in the control of cell expansion. One limitation of these studies is that the exact biochemical activity of this protein has not yet been determined. In this manuscript we produced the protein in Pichia pastoris and characterized its activity in vitro. Like other PMEIs, PMEI3 inhibits PME activity in acidic pH conditions for a variety of cell wall extracts and for purified PME preparations, but doesnt affect PME activity at neutral pH. This suggests that the previously observed in vivo effects reflect the inhibition of PME activity at low pH. The protein is remarkable heat stable and shows higher activity against PME3 than against PME2, illustrating how different members of the large PMEI family can differ in their specificities towards PME targets. Finally, application of purified PMEI3 on Arabidopsis thaliana seedlings showed a dose-dependent inhibition of homogalacturonan de-methylesterification and root growth. Purified recombinant PMEI3 is therefore a powerful tool to study the connection between pectin methylesterification and cell expansion.

plant biology↗

bioRxiv2022

The phosphoproteome is a first responder in tiered cellular adaptation to chemical stress followed by proteomics and transcriptomics alteration

Next-generation risk assessment for environmental chemicals and ingredients in consumer products involves a weight of evidence (WoE) framework integrating a suite of new approach methodologies (NAMs) based on points of departure (PoD) obtained from in vitro assays. Omics techniques provide broad coverages of the molecular toxicity pathway space. Transcriptomics assays especially play a leading role by providing relatively conservative PoDs in comparison with apical endpoints. However, it is unclear whether and how parameters measured using other omics technicquesparticipate in the cellular response to chemical perturbations, especially at exposure levels below the transcriptomically defined PoD. Multi-omics coverage may provide additional sensitive or confirmative biomarkers to complement and reduce the uncertainty in safety decisions made using targeted and transcriptomics assays. In the present study, we compared changes in transcriptomics, proteomics and phosphoproteomics with two prototype compounds, coumarin, as a main study and doxorubicin, as a complementary study to understand the sensitivity of the three omics techniques in response to chemically-induced changes in HepG2 and AC16 cells. With measurements obtained for multiple chemical concentrations and time points, we demonstrated that, compared with proteomics and transcriptomics, phosphoproteomics alterations occur not only earlier in time as expected, but also at much lower chemical concentrations and hence are proximal to the very early effects induced by chemical exposure. The phosphoproteomics changes appear to approach maximum when the transcriptomics alterations begin to be initiated. The results are consistent with a tiered framework of cellular response to chemical insults, where posttranslational modification of preexisting proteins is first seen before transcriptomics induction is engaged to launch a more energy-expensive defense that defines a useful PoD. We conclude that as the cost becomes more affordable, proteomics covering posttranslational modifications can be utilized to provide a more complete coverage of chemical-induced cellular alteration and supplement transcriptomics-based health safety decision making.

pharmacology and toxicology↗

bioRxiv2022

The Receptor Kinase FER Mediates Phase Separation of Glycine-Rich RNA-Binding Protein 7 to Confer Temperature Resilience in Arabidopsis

Temperature fluctuations repress plant growth. Although glycine-rich RNA-binding proteins (GRPs) and cold shock proteins (CSPs) have been implicated in cold adaptation, their physiological roles in the response to temperature fluctuations are largely unknown. The receptor kinase FERONIA (FER), a master regulator of cell growth, phosphorylates GRP7 within its intrinsically disordered region to modulate mRNA alternative splicing in the nucleus. Here we show that natural variations at a GRP7 residue phosphorylated by FER influences GRP7 liquid-liquid phase separation (LLPS), aiding Arabidopsis to grow over a wider temperature range. LLPS of GRP7 in the cytoplasm leads to the formation of stress granules that recruits RNAs, along with the translation machinery component eIF4E1 and mRNA chaperones, CSP1 and CSP3, to inhibit translation. Mutations in FER and the GRP7-LLPS-recruited components attenuate root growth under temperature shift conditions. Our findings illustrate the roles of GRP7 LLPS in improving plant root capacity to withstand temperature fluctuations.

plant biology↗

bioRxiv2022

dbDEMC 3.0: Functional Exploration of Differentially Expressed miRNAs in Cancers of Human and Model Organisms

microRNAs (miRNAs) are important regulators in gene expression. The deregulation of miRNA expression is widely reported in the transformation from physiological to pathological state of cells. A large amount of differentially expressed miRNAs (DEMs) have been identified in various human cancers by using high-throughput technologies, such as microarray and miRNA-seq. Through mining of published researches with high-throughput experiment information, the database of differentially expressed miRNAs in human cancers (dbDEMC) was constructed with the aim of providing a systematic resource for the storage and query of the DEMs. Here we report an update of the dbDEMC to version 3.0, containing two-fold more data entries than the previous version, now including also data from mouse and rat. The dbDEMC 3.0 contains 3,268 unique DEMs in 40 different cancer types. The current datasets for differential expression analysis have expanded to 9 generalized categories. Moreover, the current release integrates functional annotations of DEMs obtained from experimentally validated targets. The annotations can greatly benefit integrative analysis of DEMs. In summary, dbDEMC 3.0 provides a valuable resource for characterizing molecular functions and regulatory mechanisms of DEMs in human cancers. The dbDEMC 3.0 is freely accessible at https://www.biosino.org/dbDEMC.

bioinformatics↗

bioRxiv2022

Improved production and expanded application of CVS-N2c-ΔG virus for retrograde tracing

Neurotropic virus tracers, particularly those with low toxicity and high efficient tracing, are powerful tools for structural and functional dissections of neural circuits. The retrograde trans-mono-synaptic technology based on rabies virus CVS-N2c strain has reduced cytotoxicity and enhanced efficiency, attains long-term gene manipulation for functional studies, but suffers from difficult preparation and low yield. To overcome these shortcomings, an improved production system was established for rapid rescue and preparation of CVS-N2c-{Delta}G virus, CVS-N2c-{Delta}G with the same titer as SAD-B19-{Delta}G can be prepared within a short time. Meanwhile, we found that N2cG coated CVS-N2c-{Delta}G allows efficient retrograde access to projection neurons, and further expand its application in VTA/SNc to DLS pathway that unaddressed by rAAV9-Retro, and the efficiency is 6 folds higher than that of rAAV9-Retro. Then the trans-synaptic efficiency of CVS-N2c-{Delta}G virus was evaluated. Results showed that the trans-mono-synaptic efficiency of oG-mediated CVS-N2c-{Delta}G was 2-3 folds higher than that of oG-mediated SAD-B19-{Delta}G, but there was no difference between oG-mediated and N2cG-mediated CVS-N2c-{Delta}G system. In addition, codon modified N2cG (optiG) did not increase the efficiency of CVS-N2c-{Delta}G tracing. Finally, we found that the CVS-N2c-{Delta}G produced by the improved method can be used for monitoring neural activity of projection neurons, and the time window can be maintained for 3 weeks, and it can also express sufficient recombinases for efficient transgene recombination. That is, the virus produced by the improved production system does not affect its own function, paving the way for its further optimization, popularization and application in structural and functional studies of neural circuits.

neuroscience↗

bioRxiv2022

AAV11 permits efficient retrograde targeting of projection neurons

Viral tracers that permit efficient retrograde targeting of projection neurons are powerful vehicles for structural and functional dissections of the neural circuit and for the treatment of brain diseases. Recombinant adeno-associated viruses (rAAVs) are the most potential candidates because they are low-toxic with high-level transgene expression and minimal host immune responses. Currently, some rAAVs based on capsid engineering for retrograde tracing have been widely used in the analysis and manipulation of neural circuits, but suffer from brain area selectivity and inefficient retrograde transduction in certain neural connections. Here, we discovered that the recombinant adeno-associated virus 11 (rAAV11) exhibits potent retrograde labeling of projection neurons with enhanced efficiency to rAAV2-retro in some neural connections. Combined with calcium recording technology, rAAV11 can be used to monitor neuronal activities by expressing Cre recombinase or calcium-sensitive functional probe. In addition, we further showed the suitability of rAAV11 for astrocyte targeting. These properties make rAAV11 a promising tool for the mapping and manipulation of neural circuits and gene therapy of some neurological and neurodegenerative disorders. HighlightsO_LINaturally occurring AAV serotype capsid exhibits robust retrograde functionality C_LIO_LIImproved distribution properties and retrograde transport efficiency C_LIO_LICan express Cre recombinase or calcium-sensitive functional probe for neural circuits monitoring C_LIO_LICan specifically target astrocytes C_LI

neuroscience↗

bioRxiv2021

Rvb1/Rvb2 proteins couple transcription and translation during glucose starvation

During times of unpredictable stress, organisms must adapt their gene expression to maximize survival. Along with changes in transcription, one conserved means of gene regulation during conditions that quickly represses translation is the formation of cytoplasmic phase-separated mRNP granules such as P-bodies and stress granules. Previously, we identified that distinct steps in gene expression can be coupled during glucose starvation as promoter sequences in the nucleus are able to direct the subcellular localization and translatability of mRNAs in the cytosol. Here, we report that Rvb1 and Rvb2, conserved ATPase proteins implicated as protein assembly chaperones and chromatin remodelers, were enriched at the promoters and mRNAs of genes involved in alternative glucose metabolism pathways that we previously found to be transcriptionally upregulated but translationally downregulated during glucose starvation in yeast. Engineered Rvb1/Rvb2-binding on mRNAs was sufficient to sequester the mRNAs into phase-separated granules and repress their translation. Additionally, this Rvb-tethering to the mRNA drove further transcriptional upregulation of the target genes. Overall, our results point to Rvb1/Rvb2 coupling transcription, mRNA granular localization, and translatability of mRNAs during glucose starvation. This Rvb-mediated rapid gene regulation could potentially serve as an efficient recovery plan for cells after stress removal.

molecular biology↗

bioRxiv2021

CAR modulates plasma membrane nano-organization and immune signaling downstream of RALF1-FERONIA ligand-receptor signaling system

O_LIThe receptor-like kinase (RLK) FERONIA (FER) senses peptide ligands in the plasma membrane (PM), modulates plant growth and development, and integrates biotic and abiotic stress signaling for downstream adaptive response. However, the molecular interplay of these diverse processes is largely unknown. C_LIO_LIHere, we show that FER, the receptor of Rapid Alkalinization Factor 1 (RALF1), physically interacts with C2 domain ABA-related (CAR) proteins to control the nano-organization of the PM in Arabidopsis. C_LIO_LIDuring this process, the RALF1-FER pathway upregulates CAR protein translation, and then more CAR proteins are recruited to PM. This acts as a rapid feedforward loop to stabilize PM liquid-ordered phase. FER interacts with and phosphorylates CARs, and reducing their lipid-binding ability, which breaks the feedback regulation CAR activity at latter time point. C_LIO_LISimilar to FER mutant, pentuple car14569 mutants inhibit flg22-induced FLS2-BAK1 immune complex formation, which depends on the integrity of nanodomains. O_LITogether, we propose that the FER-CAR module controls the formation of the PM nano-organization during RALF signaling through a self-contained amplifying loop including both positive and negative feedbacks. C_LI C_LI

plant biology↗

bioRxiv2021

Mapping brain-wide excitatory projectome of primate prefrontal cortex at submicron resolution: relevance to diffusion tractography

Resolving trajectories of axonal pathways in the primate prefrontal cortex remains crucial to gain insights into higher-order processes of cognition and emotion, which requires a comprehensive map of axonal projections linking demarcated subdivisions of prefrontal cortex and the rest of brain. Here we report a mesoscale excitatory projectome issued from the ventrolateral prefrontal cortex (vlPFC) to the entire macaque brain by using viral-based genetic axonal tracing in tandem with high-throughput serial two-photon tomography, which demonstrated prominent monosynaptic projections to other prefrontal areas, temporal, limbic and subcortical areas, relatively weak projections to parietal and insular cortices but no projections directly to the occipital lobe. In a common 3D space, we quantitatively validated an atlas of diffusion tractography-derived vlPFC connections with correlative enhanced green fluorescent protein-labelled axonal tracing, and observed generally good agreement except a major difference in the posterior projections of inferior fronto-occipital fasciculus. These findings raise an intriguing question as to how neural information passes along long-range association fiber bundles in macaque brains, and call for the caution of using diffusion tractography to map the wiring diagram of brain circuits.

neuroscience↗

bioRxiv2021

Somatic mutation involving activated signaling, transcription, or tumor suppression is a premise of MDS evolving into AML

The transformation biology of secondary AML from MDS is still not fully understood. Here, we performed a large cohort of paired sequences including target, whole-exome and single cell sequencing to search AML transformation-related mutations (TRM). The results showed that fifty-five out of the 64 (85.9%) patients presented presumptive TRM involving activated signaling, transcription factors, or tumor suppressors. Most of TRM (63.6%, 35 cases) emerged at the leukemia transformation point. All five of the remaining nine patients analyzed by paired whole exome sequencing showed TRM which are not included in the reference targets. Single-cell sequencing indicated that the activated cell signaling route was related to TRM which take place prior to phenotypic development. Of note, defined TRM was limited to a small set of genes (less than ten, in the order: NRAS/KRAS, CEBPA, TP53, FLT3, RUNX1, CBL, PTPN11 and WT1, accounted for 91.0% of the mutations). In conclusion, somatic mutations involving in activated signaling, transcription factors, or tumor suppressors appeared to be a precondition for AML transformation from myelodysplastic syndromes. The TRM may be considered as new therapy targets.

cancer biology↗