Regulation Of Organ Development Research Articles

Organ-delimited gene regulatory networks provide high accuracy in candidate transcription factor selection across diverse processes

Organ-specific gene expression datasets that include hundreds to thousands of experiments allow the reconstruction of organ-level gene regulatory networks (GRNs). However, creating such datasets is greatly hampered by the requirements of extensive and tedious manual curation. Here, we trained a supervised classification model that can accurately classify the organ-of-origin for a plant transcriptome. This K-Nearest Neighbor-based multiclass classifier was used to create organ-specific gene expression datasets for the leaf, root, shoot, flower, and seed in Arabidopsis thaliana. A GRN inference approach was used to determine the: i. influential transcription factors (TFs) in each organ and, ii. most influential TFs for specific biological processes in that organ. These genome-wide, organ-delimited GRNs (OD-GRNs), recalled many known regulators of organ development and processes operating in those organs. Importantly, many previously unknown TF regulators were uncovered as potential regulators of these processes. As a proof-of-concept, we focused on experimentally validating the predicted TF regulators of lipid biosynthesis in seeds, an important food and biofuel trait. Of the top 20 predicted TFs, eight are known regulators of seed oil content, e.g., WRI1, LEC1, FUS3. Importantly, we validated our prediction of MybS2, TGA4, SPL12, AGL18, and DiV2 as regulators of seed lipid biosynthesis. We elucidated the molecular mechanism of MybS2 and show that it induces purple acid phosphatase family genes and lipid synthesis genes to enhance seed lipid content. This general approach has the potential to be extended to any species with sufficiently large gene expression datasets to find unique regulators of any trait-of-interest.

Periampullary cancer and neurological interactions: current understanding and future research directions.

Periampullary cancer is a malignant tumor occurring around the ampullary region of the liver and pancreas, encompassing a variety of tissue types and sharing numerous biological characteristics, including interactions with the nervous system. The nervous system plays a crucial role in regulating organ development, maintaining physiological equilibrium, and ensuring life process plasticity, a role that is equally pivotal in oncology. Investigations into nerve-tumor interactions have unveiled their key part in controlling cancer progression, inhibiting anti-tumor immune responses, facilitating invasion and metastasis, and triggering neuropathic pain. Despite many mechanisms by which nerve fibers contribute to cancer advancement still being incompletely understood, the growing emphasis on the significance of nerves within the tumor microenvironment in recent years has set the stage for the development of groundbreaking therapies. This includes combining current neuroactive medications with established therapeutic protocols. This review centers on the mechanisms of Periampullary cancer's interactions with nerves, the influence of various types of nerve innervation on cancer evolution, and outlines the horizons for ongoing and forthcoming research.

Triggering endogenous Z-RNA sensing for anti-tumor therapy through ZBP1-dependent necroptosis

ZBP1 senses viral Z-RNAs to induce necroptotic cell death to restrain viral infection. ZBP1 is also thought to recognize host cell-derived Z-RNAs to regulate organ development and tissue inflammation in mice. However, it remains unknown how the host-derived Z-RNAs are formed and how these endogenous Z-RNAs are sensed by ZBP1. Here, we report that oxidative stress strongly induces host cell endogenous Z-RNAs, and the Z-RNAs then localize to stress granules for direct sensing by ZBP1 to trigger necroptosis. Oxidative stress triggers dramatically increase Z-RNA levels in tumor cells, and the Z-RNAs then directly trigger tumor cell necroptosis through ZBP1. Localization of the induced Z-RNAs to stress granules is essential for ZBP1 sensing. Oxidative stress-induced Z-RNAs significantly promote tumor chemotherapy via ZBP1-driven necroptosis. Thus, our study identifies oxidative stress as a critical trigger for Z-RNA formation and demonstrates how Z-RNAs are directly sensed by ZBP1 to trigger anti-tumor necroptotic cell death.

Sphk1 deficiency induces apoptosis and developmental defects and premature death in zebrafish.

The sphk1 gene plays a crucial role in cell growth and signal transduction. However, the developmental functions of the sphk1 gene during early vertebrate zebrafish embryo remain not completely understood. In this study, we constructed zebrafish sphk1 mutants through CRISPR/Cas9 to investigate its role in zebrafish embryonic development. Knockout of the sphk1 gene was found to cause abnormal development in zebrafish embryos, such as darkening and atrophy of the head, trunk deformities, pericardial edema, retarded yolk sac development, reduced heart rate, and premature death. The acetylcholinesterase activity was significantly increased after the knockout of sphk1, and some of the neurodevelopmental genes and neurotransmission system-related genes were expressed abnormally. The deletion of sphk1 led to abnormal expression of immune genes, as well as a significant decrease in the number of hematopoietic stem cells and neutrophils. The mRNA levels of cardiac development-related genes were significantly decreased. In addition, cell apoptosis increases in the sphk1 mutants, and the proliferation of head cells decreases. Therefore, our study has shown that the sphk1 is a key gene for zebrafish embryonic survival and regulation of organ development. It deepened our understanding of its physiological function. Our study lays the foundation for investigating the mechanism of the sphk1 gene in early zebrafish embryonic development.

Transcriptome analysis reveals a potential regulatory mechanism of the lnc-5423.6/IGFBP5 axis in the early stages of mouse thymic involution.

Age-related thymic involution is one of the significant reasons for induced immunity decline. Recent evidence has indicated that lncRNAs are widely involved in regulating organ development. However, the lncRNA expression profiles in mouse thymic involution have not been reported. In this study, we collect mouse thymus at the ages of 1 month, 3 months, and 6 months for sequencing to observe the lncRNA and gene expression profiles in the early stages of thymic involution. Through bioinformatics analysis, a triple regulatory network of lncRNA-miRNA-mRNA that contains 29 lncRNAs, 145 miRNAs and 12 mRNAs that may be related to thymic involution is identified. Among them, IGFBP5 can reduce the viability, inhibit proliferation and promote apoptosis of mouse medullary thymic epithelial cell line 1 (MTEC1) cells through the p53 signaling pathway. In addition, miR-193b-3p can alleviate MTEC1 cell apoptosis by targeting IGFBP5. Notably, lnc-5423.6 can act as a molecular sponge of miR-193b-3p to regulate the expression of IGFBP5. In summary, lnc-5423.6 enhances the expression of IGFBP5 by adsorption of miR-193b-3p, thereby promoting MTEC1 cell apoptosis.

BZR proteins: identification, evolutionary and expression analysis under various exogenous growth regulators in plants.

The BRASSINAZOLE-RESISTANT (BZR) family of transcription factors affects a variety of developmental and physiological processes and plays a key role in multiple stress-resistance functions in plants. However, the evolutionary relationship and individual expression patterns of the BZR genes are unknown in various crop plants. In this study, we performed a genome-wide analysis of the BZR genes family in wheat and rice. Here, we found a total of 16 and 6 proteins containing the BZR domain in wheat and rice respectively. The phylogenetic analysis divided the identified BZR proteins from several plants into five subfamilies. The intron/exon structural patterns and conserved motifs distribution revealed that BZR proteins exhibite high specificities in each subfamily. Moreover, the co-expression and protein-protein interaction analysis suggested that BZR proteins may interact/co-expressed with several other proteins to perform various functions in plants. The presence of different stresses, hormones and light-responsive cis-elements in promoter regions of BZR genes imply its diverse functions in plants. The expression patterns indicated that many BZR genes regulate organ development and differentiation. BZR genes significantly respond to exogenous application of brassinosteroids, melatonin and abiotic stresses, demonstrating its key role in various developmental and physiological processes. The present study establishes the foundation for future functional genomics studies of BZR genes through reverse genetics and to further explore the potential of BZR genes in mitigating the stress tolerance in crop plants.

Characterization of the CqCAMTA gene family reveals the role of CqCAMTA03 in drought tolerance

BackgroundCalmodulin-binding transcription activators (CAMTAs) are relatively conserved calmodulin-binding transcription factors widely found in eukaryotes and play important roles in plant growth and stress response. CAMTA transcription factors have been identified in several plant species, but the family members and functions have not yet been identified and analyzed in quinoa.ResultsIn this study, we identified seven CAMTA genes across the whole quinoa genome and analyzed the expression patterns of CqCAMTAs in root and leaf tissues. Gene structure, protein domain, and phylogenetic analyses showed that the quinoa CAMTAs were structurally similar and clustered into the same three major groups as other plant CAMTAs. A large number of stress response-related cis-elements existed in the 2 kb promoter region upstream of the transcription start site of the CqCAMTA genes. qRT-PCR indicated that CqCAMTA genes were expressed differentially under PEG treatments in leaves, and responded to drought stress in leaves and roots. In particular, the CqCAMTA03 gene strongly responded to drought. The transient expression of CqCAMTA03-GFP fusion protein in the tobacco leaf showed that CqCAMTA03 was localized in the nucleus. In addition, transgenic Arabidopsis lines exhibited higher concentration levels of the antioxidant enzymes measured, including POD, SOD, and CAT, under drought conditions with very low levels of H2O2 and MDA. Moreover, relative water content and the degree of stomatal opening showed that the transgenic Arabidopsis lines were more tolerant of both stress factors as compared to their wild types.ConclusionIn this study, the structures and functions of the CAMTA family in quinoa were systematically explored. Many CAMTAs may play vital roles in the regulation of organ development, growth, and responses to drought stress. The results of the present study serve as a basis for future functional studies on the quinoa CAMTA family.

The regeneration factors ERF114 and ERF115 regulate auxin-mediated lateral root development in response to mechanical cues

Plants show an unparalleled regenerative capacity, allowing them to survive severe stress conditions, such as injury, herbivory attack, and harsh weather conditions. This potential not only replenishes tissues and restores damaged organs but can also give rise to whole plant bodies. Despite the intertwined nature of development and regeneration, common upstream cues and signaling mechanisms are largely unknown. Here, we demonstrate that in addition to being activators of regeneration, ETHYLENE RESPONSE FACTOR 114 (ERF114) and ERF115 govern developmental growth in the absence of wounding or injury. Increased ERF114 and ERF115 activity enhances auxin sensitivity, which is correlated with enhanced xylem maturation and lateral root formation, whereas their knockout results in a decrease in lateral roots. Moreover, we provide evidence that mechanical cues contribute to ERF114 and ERF115 expression in correlation with BZR1-mediated brassinosteroid signaling under both regenerative and developmental conditions. Antagonistically, cell wall integrity surveillance via mechanosensory FERONIA signaling suppresses their expression under both conditions. Taken together, our data suggest a molecular framework in which cell wall signals and mechanical strains regulate organ development and regenerative responses via ERF114- and ERF115-mediated auxin signaling.

A genetic model for in vivo proximity labelling of the mammalian secretome.

Organ functions are highly specialized and interdependent. Secreted factors regulate organ development and mediate homeostasis through serum trafficking and inter-organ communication. Enzyme-catalysed proximity labelling enables the identification of proteins within a specific cellular compartment. Here, we report a BirA*G3 mouse strain that enables CRE-dependent promiscuous biotinylation of proteins trafficking through the endoplasmic reticulum. When broadly activated throughout the mouse, widespread labelling of proteins was observed within the secretory pathway. Streptavidin affinity purification and peptide mapping by quantitative mass spectrometry (MS) proteomics revealed organ-specific secretory profiles and serum trafficking. As expected, secretory proteomes were highly enriched for signal peptide-containing proteins, highlighting both conventional and non-conventional secretory processes, and ectodomain shedding. Lower-abundance proteins with hormone-like properties were recovered and validated using orthogonal approaches. Hepatocyte-specific activation of BirA*G3 highlighted liver-specific biotinylated secretome profiles. The BirA*G3 mouse model demonstrates enhanced labelling efficiency and tissue specificity over viral transduction approaches and will facilitate a deeper understanding of secretory protein interplay in development, and in healthy and diseased adult states.

Identification of the CIPK-CBL family gene and functional characterization of CqCIPK14 gene under drought stress in quinoa

BackgroundCalcineurin-like Protein (CBL) and CBL interacting protein kinase (CIPK) play a key role in plant signal transduction and response to various environmental stimuli. Quinoa, as an important plant with high nutritional value, can meet the basic nutritional needs of human Cash crop, is also susceptible to abiotic stress. However, CBL-CIPK in quinoa have not been reported.ResultsIn this study, 16 CBL and 41 CIPK genes were identified in quinoa. CBL-CIPK gene shows different intron-exon gene structure and motif, they participate in different biological processes, and form a complex regulatory network between CBL-CIPK proteins. Many cis-regulatory element associated with ABA and drought have been found. The expression patterns of CBL-CIPK showed different expression patterns in various abiotic stresses and tissues. RT-qPCR showed that most members of these two gene families were involved in drought regulation of quinoa, in particular, the expression levels of CqCIPK11, CqCIPK15, CqCIPK37 and CqCBL13 increased significantly under drought stress.ConclusionsThe structures and functions of the CBL-CIPK family in quinoa were systematically explored. Many CBL-CIPK may play vital roles in the regulation of organ development, growth, and responses to abiotic stresses. This research has great significance for the functional characterisation of the quinoa CBL-CIPK family and our understanding of the CBL-CIPK family in higher plants.

Effect of High Glucose and Salinity on Embryological Development of Zebrafish, Brachyodanio rerio

Diabetes is a disease in which the blood glucose, or blood sugar, levels are too high. Glucose comes from the daily diet. Over time, having too much glucose in the blood can damage the eyes, the kidneys, the nerves, cause heart disease and stroke. Up to date, it is the leading disease around the world. Similarly, high blood pressure, heart disease, and kidney disease are also known to be attributed to high sodium levels. However, the effects of high salinity on embryological development post‐fertilization are yet to be researched. Danio rerio, commonly called the zebrafish, is a small freshwater fish. Its small size, short life cycle and high fecundity favor its lab uses as a test organism. It has been widely used for genetic development, transgenesis, toxicology and other genetic research due to the high conservation of gene function between zebrafish and humans. Zebrafish embryos are also transparent making them a preferable choice for developmental study. In this experiment, the effects on embryological (morphological and genetic) development were examined in the presence of a high glucose environment and high salinity conditions were examined. Zebrafish eggs were treated with normal media and high glucose for 5 days from 3 hours post‐fertilization(hpf) to 96hpf separately as control and experimental groups. RNA is extracted from control and experimental group to determine five genes’ change in high glucose group using PCR. Day 5 Larva is fixed in 10% formalin for H&E staining to detect organogenesis changes under high glucose conditions. Three progenitor genes that regulate organ development will be detected for protein level changes in experimental group by immunohistochemistry. Zebrafish eggs were treated with normal media and high salt (2%) for 3 days from 3 hpf to 72hpf separately as control and experimental groups. Day 1 and Day 2 larvae are fixed in 10% formalin for H&E staining. Glucose delayed the zebrafish embryo development by slowing the hatch rate about 24 hours. The brain, heart, and tail started showing morphology smaller in the glucose group compared to the control group at 24 hpf. Heartbeat is slower in the glucose group compared to the control group on day 2 and 3 with a statistically significant difference. The brain, heart, and tail started showing morphology smaller in the salt group compared to the control group at 48 hpf. These conditions contribute to significant physiological differences that may provide insight on functionality post‐embryological development. Testing to find consistent trends in morphology and genetic differences in high salt conditions, and genetic alterations for high glucose conditions are being further researched in this experiment.

Genome-wide identification and expression analysis of the bZIP transcription factor family genes in response to abiotic stress in Nicotiana tabacum L.

BackgroundThe basic leucine zipper (bZIP) transcription factor (TF) is one of the largest families of transcription factors (TFs). It is widely distributed and highly conserved in animals, plants, and microorganisms. Previous studies have shown that the bZIP TF family is involved in plant growth, development, and stress responses. The bZIP family has been studied in many plants; however, there is little research on the bZIP gene family in tobacco.ResultsIn this study, 77 bZIPs were identified in tobacco and named NtbZIP01 through to NtbZIP77. These 77 genes were then divided into eleven subfamilies according to their homology with Arabidopsis thaliana. NtbZIPs were unevenly distributed across twenty-two tobacco chromosomes, and we found sixteen pairs of segmental duplication. We further studied the collinearity between these genes and related genes of six other species. Quantitative real-time polymerase chain reaction analysis identified that expression patterns of bZIPs differed, including in different organs and under various abiotic stresses. NtbZIP49 might be important in the development of flowers and fruits; NtbZIP18 might be an important regulator in abiotic stress.ConclusionsIn this study, the structures and functions of the bZIP family in tobacco were systematically explored. Many bZIPs may play vital roles in the regulation of organ development, growth, and responses to abiotic stresses. This research has great significance for the functional characterisation of the tobacco bZIP family and our understanding of the bZIP family in higher plants.

Development of a Vascularised Cardiac Organoid Platform Reveals a Regulatory Role for Extracellular Matrix Environment on Muscle Functionality

Multicellular composition of the heart is important for regulating organ development and responses to injury, however the role of cardiac cell types in organ maturation is not well characterised. In this study we characterised a vascularised cardiac organoid model (vhCO) derived from human pluripotent stem cells to better understand cell-cell interactions in human heart tissue. We show that endothelial cells in vhCO increase organoid force of contraction and enhance the expression of mature sarcomeric proteins and extracellular matrix (ECM) components.

Targeting-YAP/TAZ therapies for head and neck cancer, directly or indirectly?

YAP/TAZ are wild over-activated in head and neck squamous cell carcinoma (HNSCC) with high potential as a direct therapy target for HNSCC treatments. However, the efforts on the directly targeting-YAP/TAZ therapies over the past decade, have very limited impacts, mainly caused by: 1. There is still none effective and specific YAP/TAZ inhibitor with clinical potential; 2. YAP/TAZ might not be directly targeted, because of their multiple important biological functions, such as: regulation of cell proliferation and survival, stem cell maintain, regulation of organ development, organ size control, and tissue regeneration. Interestingly, the over-activation of YAP/TAZ in HNSCC mainly be regulated by upstream abnormal molecular or biological events, instead of genes alteration of YAP/TAZ. Therefore, exploring the alternative molecular events regulating YAP/TAZ activation and molecular mechanism in HNSCC might help to uncover novel indirect targets of YAP/TAZ therapies for HNSCC prevention and treatment.

Calcium, an Emerging Intracellular Messenger for the Hippo Pathway Regulation.

The Hippo pathway is a conserved signaling network regulating organ development and tissue homeostasis. Dysfunction of this pathway may lead to various diseases, such as regeneration defect and cancer. Studies over the past decade have found various extracellular and intracellular signals that can regulate this pathway. Among them, calcium (Ca2+) is emerging as a potential messenger that can transduce certain signals, such as the mechanical cue, to the main signaling machinery. In this process, rearrangement of the actin cytoskeleton, such as calcium-activated actin reset (CaAR), may construct actin filaments at the cell cortex or other subcellular domains that provide a scaffold to launch Hippo pathway activators. This article will review studies demonstrating Ca2+-mediated Hippo pathway modulation and discuss its implication in understanding the role of actin cytoskeleton in regulating the Hippo pathway.

Phosphosite T674A mutation in kinesin family member 3A fails to reproduce tissue and ciliary defects characteristic of CILK1 loss of function.

Kinesin family member 3A (KIF3A) is a molecular motor protein in the heterotrimeric kinesin-2 complex that drives anterograde intraflagellar transport. This process plays a pivotal role in both biogenesis and maintenance of the primary cilium that supports tissue development. Ciliogenesis associated kinase 1 (CILK1) phosphorylates human KIF3A at Thr672. CILK1 loss of function causes ciliopathies that manifest profound and multiplex developmental defects, including hydrocephalus, polydactyly, shortened and hypoplastic bones and alveoli airspace deficiency, leading to perinatal lethality. Prior studies have raised the hypothesis that CILK1 phosphorylation of KIF3A is critical for its regulation of organ development. We produced a mouse model with phosphorylation site Thr674 in mouse Kif3a mutated to Ala. Kif3a T674A homozygotes are viable and exhibit no skeletal and brain abnormalities, and only mildly reduced airspace in alveoli. Mouse embryonic fibroblasts carrying Kif3a T674A mutation show a normal rate of ciliation and a moderate increase in cilia length. These results indicate that eliminating Kif3a Thr674 phosphorylation by Cilk1 is insufficient to reproduce the severe developmental defects in ciliopathies caused by Cilk1 loss of function. This suggests KIF3A-Thr672 phosphorylation by CILK1 is not essential for tissue development and other substrates are involved in CILK1 ciliopathies.

Identification and Expression Analysis of Strigolactone Biosynthetic and Signaling Genes in Response to Salt and Alkaline Stresses in Soybean (Glycine max).

Strigolactones (SLs) are the major plant hormones that play important roles in regulating organ development and environmental stress tolerance in plants. Even though the SL-related genes have been identified and well characterized in some plants, the information of SL-related genes in soybean is not fully established yet, especially in response to salt and alkaline stresses. In this study, we identified nine SL biosynthetic genes that include two D27, two CCD7, two CCD8, and three MAX1, as well as seven SL signaling genes that comprised two D14, two MAX2, and three D53 in the soybean genome. We found that SL biosynthetic and signaling genes are evolutionary conserved among different species. Syntenic analysis of these genes revealed their location on nine chromosomes as well as the presence of 10 pairs of duplication genes. Moreover, plant hormone and stress-responsive elements were identified in the promoter regions of SL biosynthetic and signaling genes. By using reverse transcription quantitative real-time PCR, we confirmed that SL genes have different tissue expressions in roots, stems, and leaves. The expression profile of SL biosynthetic and signaling genes under salt and alkaline stresses further confirmed the regulatory roles of SL biosynthetic and signaling genes under stress. In conclusion, we identified and provided valuable information on the soybean SL biosynthetic and signaling genes, and established a foundation for further functional analysis of soybean SL-related genes in response to salt and alkaline stresses.

H2S-Releasing Composite: a Gasotransmitter Platform for Potential Biomedical Applications.

Hydrogen sulfide (H2S) is an endogenous gasotransmitter in the human body involved in various physiological functions including cytoprotection, maintaining homeostasis, and regulation of organ development. Therefore, H2S-releasing polymers that can imitate endogenous H2S release can offer great therapeutic potential. Despite decades of research, the use of H2S donors in medical device applications is mostly unexplored largely due to the challenge of the steady H2S release from a suitable polymeric platform that does not compromise the normal cellular functions of the host. In this work, an exogenous H2S release system was developed by integrating sodium sulfide (Na2S), a common H2S donor, into a medical-grade thermoplastic silicone-polycarbonate-urethane polymer, Carbosil 20 80A (hereon as Carbosil), via a facile solvent evaporation technique. The spatial distribution and nature of Na2S in Carbosil were characterized through X-ray diffraction (XRD) spectroscopy and field emission scanning electron microscopy (FESEM) with energy-dispersive spectroscopy (EDS), indicating an amorphous phase shift upon incorporating Na2S in Carbosil. The composite, Na2S-Carbosil, is responsive in physiological conditions, resulting in sustained H2S release measured for 3 h. In vitro cellular responses of 3T3 mouse fibroblasts, human lung epithelial (HLE), and primary human umbilical vein endothelial cells (HUVEC) were investigated. Fibroblast cells showed cell proliferation in 24 h and complete cell migration in 42 h in vitro. The Na2S-Carbosil composites were cytocompatible toward HUVEC and HLE cells. This study provided important in vitro proof of concept that warrants potential use of these H2S-releasing platforms in engineering biomedical devices, tissue engineering, and drug delivery applications.

Evolution and roles of cytokinin genes in angiosperms 2: Do ancient CKXs play housekeeping roles while non-ancient CKXs play regulatory roles?

Cytokinin oxidase/dehydrogenase (CKX) is a key enzyme responsible for the degradation of endogenous cytokinins. However, the origins and roles of CKX genes in angiosperm evolution remain unclear. Based on comprehensive bioinformatic and transgenic plant analyses, we demonstrate that the CKXs of land plants most likely originated from an ancient chlamydial endosymbiont during primary endosymbiosis. We refer to the CKXs retaining evolutionarily ancient characteristics as “ancient CKXs” and those that have expanded and functionally diverged in angiosperms as “non-ancient CKXs”. We show that the expression of some non-ancient CKXs is rapidly inducible within 15 min upon the dehydration of Arabidopsis, while the ancient CKX (AtCKX7) is not drought responsive. Tobacco plants overexpressing a non-ancient CKX display improved oxidative and drought tolerance and root growth. Previous mutant studies have shown that non-ancient CKXs regulate organ development, particularly that of flowers. Furthermore, ancient CKXs preferentially degrade cis-zeatin (cZ)-type cytokinins, while non-ancient CKXs preferentially target N6-(Δ2-isopentenyl) adenines (iPs) and trans-zeatins (tZs). Based on the results of this work, an accompanying study (Wang et al. https://doi.org/10.1038/s41438-019-0211-x) and previous studies, we hypothesize that non-ancient CKXs and their preferred substrates of iP/tZ-type cytokinins regulate angiosperm organ development and environmental stress responses, while ancient CKXs and their preferred substrates of cZs play a housekeeping role, which echoes the conclusions and hypothesis described in the accompanying report (Wang, X. et al. Evolution and roles of cytokinin genes in angiosperms 1: Doancient IPTs play housekeeping while non-ancient IPTs play regulatory roles? Hortic Res7, (2020). https://doi.org/10.1038/s41438-019-0211-x).

Gene Expression Profiles Controlled by the Alternative Splicing Factor Nova2 in Endothelial Cells.

Alternative splicing (AS) plays an important role in expanding the complexity of the human genome through the production of specialized proteins regulating organ development and physiological functions, as well as contributing to several pathological conditions. How AS programs impact on the signaling pathways controlling endothelial cell (EC) functions and vascular development is largely unknown. Here we identified, through RNA-seq, changes in mRNA steady-state levels in ECs caused by the neuro-oncological ventral antigen 2 (Nova2), a key AS regulator of the vascular morphogenesis. Bioinformatics analyses identified significant enrichment for genes regulated by peroxisome proliferator-activated receptor-gamma (Ppar-γ) and E2F1 transcription factors. We also showed that Nova2 in ECs controlled the AS profiles of Ppar-γ and E2F dimerization partner 2 (Tfdp2), thus generating different protein isoforms with distinct function (Ppar-γ) or subcellular localization (Tfdp2). Collectively, our results supported a mechanism whereby Nova2 integrated splicing decisions in order to regulate Ppar-γ and E2F1 activities. Our data added a layer to the sequential series of events controlled by Nova2 in ECs to orchestrate vascular biology.