The maize PLASTID TERMINAL OXIDASE (PTOX) locus controls the carotenoid content of kernels.

Carotenoids perform a broad range of important functions in humans; therefore, carotenoid biofortification of maize (Zea mays L.), one of the most highly produced cereal crops worldwide, would have a global impact on human health. PLASTID TERMINAL OXIDASE (PTOX) genes play an important role in carotenoid metabolism; however, the possible function of PTOX in carotenoid biosynthesis in maize has not yet been explored. In this study, we characterized the maize PTOX locus by forward- and reverse-genetic analyses. While most higher plant species possess a single copy of the PTOX gene, maize carries two tandemly duplicated copies. Characterization of mutants revealed that disruption of either copy resulted in a carotenoid-deficient phenotype. We identified mutations in the PTOX genes as being causal of the classic maize mutant, albescent1. Remarkably, overexpression of ZmPTOX1 significantly improved the content of carotenoids, especially ß-carotene (provitamin A), which was increased by ~threefold, in maize kernels. Overall, our study shows that maize PTOX locus plays an important role in carotenoid biosynthesis in maize kernels and suggests that fine-tuning the expression of this gene could improve the nutritional value of cereal grains.

A Galectin-9-Driven CD11chigh Decidual Macrophage Subset Suppresses Uterine Vascular Remodeling in Preeclampsia.

BACKGROUND: Preeclampsia is a serious disease of pregnancy that lacks early diagnosis methods or effective treatment, except delivery. Dysregulated uterine immune cells and spiral arteries are implicated in preeclampsia, but the mechanistic link remains unclear. METHODS: Single-cell RNA sequencing and spatial transcriptomics were used to identify immune cell subsets associated with preeclampsia. Cell-based studies and animal models including conditional knockout mice and a new preeclampsia mouse model induced by recombinant mouse galectin-9 were applied to validate the pathogenic role of a CD11chigh subpopulation of decidual macrophages (dMφ) and to determine its underlying regulatory mechanisms in preeclampsia. A retrospective preeclampsia cohort study was performed to determine the value of circulating galectin-9 in predicting preeclampsia. RESULTS: We discovered a distinct CD11chigh dMφ subset that inhibits spiral artery remodeling in preeclampsia. The proinflammatory CD11chigh dMφ exhibits perivascular enrichment in the decidua from patients with preeclampsia. We also showed that trophoblast-derived galectin-9 activates CD11chigh dMφ by means of CD44 binding to suppress spiral artery remodeling. In 3 independent preeclampsia mouse models, placental and plasma galectin-9 levels were elevated. Galectin-9 administration in mice induces preeclampsia-like phenotypes with increased CD11chigh dMφ and defective spiral arteries, whereas galectin-9 blockade or macrophage-specific CD44 deletion prevents such phenotypes. In pregnant women, increased circulating galectin-9 levels in the first trimester and at 16 to 20 gestational weeks can predict subsequent preeclampsia onset. CONCLUSIONS: These findings highlight a key role of a distinct perivascular inflammatory CD11chigh dMφ subpopulation in the pathogenesis of preeclampsia. CD11chigh dMφ activated by increased galectin-9 from trophoblasts suppresses uterine spiral artery remodeling, contributing to preeclampsia. Increased circulating galectin-9 may be a biomarker for preeclampsia prediction and intervention.

Weak allele versus null allele: which one to select?

Maize and rice were domesticated from their wild progenitors independently. Whether their convergent phenotypic selection was driven by conserved molecular changes remains unclear. We discuss the implications of a recent genome-wide study of convergently selected maize and rice genes showing that maize KERNEL ROW NUMBER2 (KRN2) and its rice ortholog experienced convergent selection.

Golgi α-mannosidases regulate cell surface N-glycan type and ectodomain shedding of the transmembrane protease corin.

Corin is a transmembrane protease that activates natriuretic peptides on the cell membrane. Reduced cell surface targeting or increased ectodomain shedding disrupts cell membrane homeostasis of corin, thereby impairing its cell surface expression and enzyme activity. N-glycans are essential in corin ectodomain shedding. Lack of N-glycans promotes corin ectodomain shedding in the juxtamembrane and frizzled-1 domains. The nascent N-glycans, transferred onto the polypeptide of corin, undergo multistep N-glycan processing in the endoplasmic reticulum and Golgi. It remains unclear how trimming by Golgi α-mannosidases, the critical N-glycan processing steps in N-glycan maturation, may regulate corin biosynthesis. In this study, we examined the effects of kifunensine and swainsonine, the inhibitors for α-mannosidases I and II, on corin expression and function. Western analysis of corin proteins in cell lysates and conditioned media from the inhibitor-treated corin-stable HEK293 cells and AC16 cells showed that both α-mannosidases I and II were required to maintain complex N-glycans on cell surface corin and protect corin from ectodomain shedding in the juxtamembrane and frizzled-1 domains. Cell viability analysis revealed that inhibition of α-mannosidase I or II sensitized cardiomyocytes to hydrogen peroxide-induced injury via regulating corin. Moreover, either one of the two coding genes was sufficient to perform Golgi α-mannosidase I trimming of N-glycans on corin. Similarly, this sufficiency was observed in Golgi α-mannosidase II-coding genes. Inhibition of ectodomain shedding restored corin zymogen activation from kifunensine- or swainsonine-induced reduction. Together, our results show the important roles of Golgi α-mannosidases in maintaining cell membrane homeostasis and biological activities of corin.

Dynamic transcriptome landscape of developing maize ear.

Seed number and harvesting ability in maize (Zea mays L.) are primarily determined by the architecture of female inflorescence, namely the ear. Therefore, ear morphogenesis contributes to grain yield and as such is one of the key target traits during maize breeding. However, the molecular networks of this highly dynamic and complex grain-bearing inflorescence remain largely unclear. As a first step toward characterizing these networks, we performed a high-spatio-temporal-resolution investigation of transcriptomes using 130 ear samples collected from developing ears with length from 0.1 mm to 19.0 cm. Comparisons of these mRNA populations indicated that these spatio-temporal transcriptomes were clearly separated into four distinct stages stages I, II, III, and IV. A total of 23 793 genes including 1513 transcription factors (TFs) were identified in the investigated developing ears. During the stage I of ear morphogenesis, 425 genes were predicted to be involved in a co-expression network established by eight hub TFs. Moreover, 9714 ear-specific genes were identified in the seven kinds of meristems. Additionally, 527 genes including 59 TFs were identified as especially expressed in ear and displayed high temporal specificity. These results provide a high-resolution atlas of gene activity during ear development and help to unravel the regulatory modules associated with the differentiation of the ear in maize.

Protein tyrosine phosphatase PTPN22 negatively modulates platelet function and thrombus formation.

Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) is a protein tyrosine phosphatase that negatively regulates T-cell signaling. However, whether it is expressed and functions in platelets remains unknown. Here we investigated the expression and role of PTPN22 in platelet function. We reported PTPN22 expression in both human and mouse platelets. Using PTPN22-/- mice, we showed that PTPN22 deficiency significantly shortened tail-bleeding time and accelerated arterial thrombus formation without affecting venous thrombosis and the coagulation factors VIII and IX. Consistently, PTPN22-deficient platelets exhibited enhanced platelet aggregation, granule secretion, calcium mobilization, lamellipodia formation, spreading, and clot retraction. Quantitative phosphoproteomic analysis revealed the significant difference of phosphodiesterase 5A (PDE5A) phosphorylation in PTPN22-deficient platelets compared with wild-type platelets after collagen-related peptide stimulation, which was confirmed by increased PDE5A phosphorylation (Ser92) in collagen-related peptide-treated PTPN22-deficient platelets, concomitant with reduced level and vasodilator-stimulated phosphoprotein phosphorylation (Ser157/239). In addition, PTPN22 interacted with phosphorylated PDE5A (Ser92) and dephosphorylated it in activated platelets. Moreover, purified PTPN22 but not the mutant form (C227S) possesses intrinsic serine phosphatase activity. Furthermore, inhibition of PTPN22 enhanced human platelet aggregation, spreading, clot retraction, and increased PDE5A phosphorylation (Ser92). In conclusion, our study shows a novel role of PTPN22 in platelet function and arterial thrombosis, identifying new potential targets for future prevention of thrombotic or cardiovascular diseases.

The protease corin regulates electrolyte homeostasis in eccrine sweat glands.

Sweating is a basic skin function in body temperature control. In sweat glands, salt excretion and reabsorption are regulated to avoid electrolyte imbalance. To date, the mechanism underlying such regulation is not fully understood. Corin is a transmembrane protease that activates atrial natriuretic peptide (ANP), a cardiac hormone essential for normal blood volume and pressure. Here, we report an unexpected role of corin in sweat glands to promote sweat and salt excretion in regulating electrolyte homeostasis. In human and mouse eccrine sweat glands, corin and ANP are expressed in the luminal epithelial cells. In corin-deficient mice on normal- and high-salt diets, sweat and salt excretion is reduced. This phenotype is associated with enhanced epithelial sodium channel (ENaC) activity that mediates Na+ and water reabsorption. Treatment of amiloride, an ENaC inhibitor, normalizes sweat and salt excretion in corin-deficient mice. Moreover, treatment of aldosterone decreases sweat and salt excretion in wild-type (WT), but not corin-deficient, mice. These results reveal an important regulatory function of corin in eccrine sweat glands to promote sweat and salt excretion.

m6A-mediated upregulation of miRNA-193a aggravates cardiomyocyte apoptosis and inflammatory response in sepsis-induced cardiomyopathy via the METTL3/ miRNA-193a/BCL2L2 pathway.

The impact of N6-methyladenosine (m6A) modification on pri-miRNA in sepsis-induced cardiomyopathy (SICM), and its underlying regulatory mechanism, have not been fully elucidated. We successfully constructed a SICM mice model through cecal ligation and puncture (CLP). In vitro, a lipopolysaccharide (LPS)-induced HL-1 cells model was also established. The results showed that sepsis frequently resulted in excessive inflammatory response concomitant with impaired myocardial function in mice exposed to CLP, as indicated by decreases in ejection fraction (EF), fraction shortening (FS), and left ventricular end diastolic diameters (LVDd). miR-193a was enriched in CLP mice heart and in LPS-treated HL-1 cells, while overexpression of miR-193a significantly increased the expression levels of cytokines. Sepsis-induced enrichment of miR-193a significantly inhibited cardiomyocytes proliferation and enhanced apoptosis, while this was reversed by miR-193a knockdown. Furthermore, under our experimental conditions, enrichment of miR-193a in SICM could be considered excessively maturated on pri-miR-193a by enhanced m6A modification. This modification was catalyzed by sepsis-induced overexpression of methyltransferase-like 3 (METTL3). Moreover, mature miRNA-193a bound to a predictive sequence within 3'UTRs of a downstream target, BCL2L2, which was further validated by the observation that the BCL2L2-3'UTR mutant failed to decrease luciferase activity when co-transfected with miRNA-193a. The interaction between miRNA-193a and BCL2L2 resulted in BCL2L2 downregulation, subsequently activating the caspase-3 apoptotic pathway. In conclusion, sepsis-induced miR-193a enrichment via m6A modification plays an essential regulatory role in cardiomyocyte apoptosis and inflammatory response in SICM. The detrimental axis of METTL3/m6A/miR-193a/BCL2L2 is implicated in the development of SICM.

Expediting Next-Generation Hybrid Technology in Recalcitrant Maize Inbreds through In Vivo Targeted Activity of CRISPR/Cas9.

The Manipulated Genic Male Sterile Maintainer (MGM) system, a next-generation hybrid seed technology, enables efficient production of sortable seeds from genic male sterile (GMS) lines. However, implementing robust MGM systems in commercial maize inbred lines requires stable transformation, a genotype-specific and laborious process. This study aimed to integrate MGM technology into the commercial maize inbred line Z372, developing both GMS and MGM lines. We utilized the MGM line ZC01-3A-7, which contains the MS26ΔE5 editor T-DNA and MGM T-DNA, previously established in the highly transformable ZC01 recipient plants. Through a combination of crossing and backcrossing with Z372, we targeted the fertility gene Ms26 within the Z372 genome for mutation using the in vivo CRISPR/Cas9 activity within the MS26ΔE5 editor T-DNA construct. This approach facilitated precise editing of the Ms26 locus, minimizing linkage drag associated with the Ms26 mutation. Whole-genome SNP analysis achieved a 98.74% recovery rate for GMS and 96.32% for MGM in the BC2F2 generation. Importantly, the Z372-GMS line with the ms26ΔE5 mutation is non-transgenic, avoiding linkage drag and demonstrating production readiness. This study represents a significant advancement in maize breeding, enabling the rapid generation of GMS and MGM lines for efficient hybrid seed production.

Transmembrane serine protease TMPRSS2 implicated in SARS-CoV-2 infection is autoactivated intracellularly and requires N-glycosylation for regulation.

Transmembrane protease serine 2 (TMPRSS2) is a membrane-bound protease expressed in many human epithelial tissues, including the airway and lung. TMPRSS2-mediated cleavage of viral spike protein is a key mechanism in severe acute respiratory syndrome coronavirus 2 activation and host cell entry. To date, the cellular mechanisms that regulate TMPRSS2 activity and cell surface expression are not fully characterized. In this study, we examined two major post-translational events, zymogen activation and N-glycosylation, in human TMPRSS2. In experiments with human embryonic kidney 293, bronchial epithelial 16HBE, and lung alveolar epithelial A549 cells, we found that TMPRSS2 was activated via intracellular autocatalysis and that this process was blocked in the presence of hepatocyte growth factor activator inhibitors 1 and 2. By glycosidase digestion and site-directed mutagenesis, we showed that human TMPRSS2 was N-glycosylated. N-glycosylation at an evolutionarily conserved site in the scavenger receptor cysteine-rich domain was required for calnexin-assisted protein folding in the endoplasmic reticulum and subsequent intracellular trafficking, zymogen activation, and cell surface expression. Moreover, we showed that TMPRSS2 cleaved severe acute respiratory syndrome coronavirus 2 spike protein intracellularly in human embryonic kidney 293 cells. These results provide new insights into the cellular mechanism in regulating TMPRSS2 biosynthesis and function. Our findings should help to understand the role of TMPRSS2 in major respiratory viral diseases.

Hepsin regulates TGFß signaling via fibronectin proteolysis.

Transforming growth factor-beta (TGFß) is a multifunctional cytokine with a well-established role in mammary gland development and both oncogenic and tumor-suppressive functions. The extracellular matrix (ECM) indirectly regulates TGFß activity by acting as a storage compartment of latent-TGFß, but how TGFß is released from the ECM via proteolytic mechanisms remains largely unknown. In this study, we demonstrate that hepsin, a type II transmembrane protease overexpressed in 70% of breast tumors, promotes canonical TGFß signaling through the release of latent-TGFß from the ECM storage compartment. Mammary glands in hepsin CRISPR knockout mice showed reduced TGFß signaling and increased epithelial branching, accompanied by increased levels of fibronectin and latent-TGFß1, while overexpression of hepsin in mammary tumors increased TGFß signaling. Cell-free and cell-based experiments showed that hepsin is capable of direct proteolytic cleavage of fibronectin but not latent-TGFß and, importantly, that the ability of hepsin to activate TGFß signaling is dependent on fibronectin. Altogether, this study demonstrates a role for hepsin as a regulator of the TGFß pathway in the mammary gland via a novel mechanism involving proteolytic downmodulation of fibronectin.

Patterns of allergic sensitization in adults with severe asthma: the ATLAS non-interventional study.

OBJECTIVES: Severe asthma is heterogeneous, with childhood-onset asthma believed more likely to be allergic, whereas adult-onset asthma is considered typically non-allergic. However, the allergic diagnosis is typically by exclusion: if patients do not react to an allergen panel, which is not standardized and often limited to few allergens, they are considered non-allergic. The overall aim of the ATLAS study was to characterize the sensitization to allergens in severe asthma (independent of phenotype). METHODS: Single-visit, cross-sectional, non-interventional study in adults with severe asthma. Analyses were conducted for total and specific immunoglobulin E against 53 allergens, overall and in subgroups, including age at asthma onset (<20 [childhood-onset] and >40 years of age). RESULTS: Among 1010 recruited patients, 28.4% reported childhood-onset asthma and 33.6% onset >40 years of age. After excluding patients receiving omalizumab/anti-IL5 therapy, 27.6% were not sensitized to any tested allergens, whereas 19.1% were sensitized to >10 allergens. All allergens triggered sensitization in some patients. Baseline characteristics in the two onset subgroups were similar; 23.2% with childhood-onset asthma were not sensitized to any allergen, compared to 32.0% with onset >40 years of age. CONCLUSION: When a broad panel of allergens is used for sensitization testing, as many as three quarters of patients with severe asthma display sensitivity to at least one allergen, with substantial overlaps in all characteristics between the two age-at-onset subgroups. All of the tested allergens triggered a response in at least some patients, emphasizing the importance of including a broad range of allergens in any testing panel.

Hepsin enhances liver metabolism and inhibits adipocyte browning in mice.

Hepsin is a transmembrane serine protease primarily expressed in the liver. To date, the physiological function of hepsin remains poorly defined. Here we report that hepsin-deficient mice have low levels of blood glucose and lipids and liver glycogen, but increased adipose tissue browning and basal metabolic rates. The phenotype is caused by reduced hepatocyte growth factor activation and impaired Met signaling, resulting in decreased liver glucose and lipid metabolism and enhanced adipocyte browning. Hepsin-deficient mice exhibit marked resistance to high-fat diet-induced obesity, hyperglycemia, and hyperlipidemia. In db/db mice, hepsin deficiency ameliorates obesity and diabetes. These data indicate that hepsin is a key regulator in liver metabolism and energy homeostasis, suggesting that hepsin could be a therapeutic target for treating obesity and diabetes.

The maize heterotrimeric G protein ß subunit controls shoot meristem development and immune responses.

Heterotrimeric G proteins are important transducers of receptor signaling, functioning in plants with CLAVATA receptors in controlling shoot meristem size and with pathogen-associated molecular pattern receptors in basal immunity. However, whether specific members of the heterotrimeric complex potentiate cross-talk between development and defense, and the extent to which these functions are conserved across species, have not yet been addressed. Here we used CRISPR/Cas9 to knock out the maize G protein ß subunit gene (Gß) and found that the mutants are lethal, differing from those in Arabidopsis, in which homologous mutants have normal growth and fertility. We show that lethality is caused not by a specific developmental arrest, but by autoimmunity. We used a genetic diversity screen to suppress the lethal Gß phenotype and also identified a maize Gß allele with weak autoimmune responses but strong development phenotypes. Using these tools, we show that Gß controls meristem size in maize, acting epistatically with G protein α subunit gene (Gα), suggesting that Gß and Gα function in a common signaling complex. Furthermore, we used an association study to show that natural variation in Gß influences maize kernel row number, an important agronomic trait. Our results demonstrate the dual role of Gß in immunity and development in a cereal crop and suggest that it functions in cross-talk between these competing signaling networks. Therefore, modification of Gß has the potential to optimize the trade-off between growth and defense signaling to improve agronomic production.

Krüppel-like factor 17 upregulates uterine corin expression and promotes spiral artery remodeling in pregnancy.

Spiral artery remodeling is an important physiological process in the pregnant uterus which increases blood flow to the fetus. Impaired spiral artery remodeling contributes to preeclampsia, a major disease in pregnancy. Corin, a transmembrane serine protease, is up-regulated in the pregnant uterus to promote spiral artery remodeling. To date, the mechanism underlying uterine corin up-regulation remains unknown. Here we show that Krüppel-like factor (KLF) 17 is a key transcription factor for uterine corin expression in pregnancy. In cultured human uterine endometrial cells, KLF17 binds to the CORIN promoter and enhances the promoter activity. Disruption of the KLF17 gene in the endometrial cells abolishes CORIN expression. In mice, Klf17 is up-regulated in the pregnant uterus. Klf17 deficiency prevents uterine Corin expression in pregnancy. Moreover, Klf17-deficient mice have poorly remodeled uterine spiral arteries and develop gestational hypertension and proteinuria. Together, our results reveal an important function of KLF17 in regulating Corin expression and uterine physiology in pregnancy.

High-throughput discovery of genetic determinants of circadian misalignment.

Circadian systems provide a fitness advantage to organisms by allowing them to adapt to daily changes of environmental cues, such as light/dark cycles. The molecular mechanism underlying the circadian clock has been well characterized. However, how internal circadian clocks are entrained with regular daily light/dark cycles remains unclear. By collecting and analyzing indirect calorimetry (IC) data from more than 2000 wild-type mice available from the International Mouse Phenotyping Consortium (IMPC), we show that the onset time and peak phase of activity and food intake rhythms are reliable parameters for screening defects of circadian misalignment. We developed a machine learning algorithm to quantify these two parameters in our misalignment screen (SyncScreener) with existing datasets and used it to screen 750 mutant mouse lines from five IMPC phenotyping centres. Mutants of five genes (Slc7a11, Rhbdl1, Spop, Ctc1 and Oxtr) were found to be associated with altered patterns of activity or food intake. By further studying the Slc7a11tm1a/tm1a mice, we confirmed its advanced activity phase phenotype in response to a simulated jetlag and skeleton photoperiod stimuli. Disruption of Slc7a11 affected the intercellular communication in the suprachiasmatic nucleus, suggesting a defect in synchronization of clock neurons. Our study has established a systematic phenotype analysis approach that can be used to uncover the mechanism of circadian entrainment in mice.

Natriuretic Peptide Signaling in Uterine Biology and Preeclampsia.

Endometrial decidualization is a uterine process essential for spiral artery remodeling, embryo implantation, and trophoblast invasion. Defects in endometrial decidualization and spiral artery remodeling are important contributing factors in preeclampsia, a major disorder in pregnancy. Atrial natriuretic peptide (ANP) is a cardiac hormone that regulates blood volume and pressure. ANP is also generated in non-cardiac tissues, such as the uterus and placenta. In recent human genome-wide association studies, multiple loci with genes involved in natriuretic peptide signaling are associated with gestational hypertension and preeclampsia. In cellular experiments and mouse models, uterine ANP has been shown to stimulate endometrial decidualization, increase TNF-related apoptosis-inducing ligand expression and secretion, and enhance apoptosis in arterial smooth muscle cells and endothelial cells. In placental trophoblasts, ANP stimulates adenosine 5'-monophosphate-activated protein kinase and the mammalian target of rapamycin complex 1 signaling, leading to autophagy inhibition and protein kinase N3 upregulation, thereby increasing trophoblast invasiveness. ANP deficiency impairs endometrial decidualization and spiral artery remodeling, causing a preeclampsia-like phenotype in mice. These findings indicate the importance of natriuretic peptide signaling in pregnancy. This review discusses the role of ANP in uterine biology and potential implications of impaired ANP signaling in preeclampsia.

Enhanced nitrogen and phosphorus removal by a novel ecological floating bed integrated with three-dimensional biofilm electrode system.

The ecological floating bed (EFB) has been used extensively for the purification of eutrophication water. However, the traditional EFB (T-EFB) often exhibits a decline in nitrogen and phosphorus removal because of the limited adsorption capacity of fillers and inadequate electron donors. In the present study, a series of electrolysis-ecological floating beds (EC-EFBs) were constructed to investigate the decontamination performance of conventional pollutants. EC-EFB outperformed T-EFB in terms of nitrogen and phosphorus removal. Its removal efficiency of total nitrogen and total phosphorus was 20.51-32.95% and 45.06-96.20%, which were higher than that in T-EFB.. Moreover, the plants in EC-EFB demonstrated higher metabolic activity than those in T-EFB. Under the electrolysis condition of 0.51 mA/cm2 for 24 h, the malondialdehyde content and superoxide dismutase activity in EC-EFB were 6.08 nmol/g and 22.61 U/g, which were significantly lower compared to T-EFB (38.65 nmol/g and 26.13 U/g). And the soluble protein content of plant leaves increased from 3.31 mg/g to 5.72 mg/g in EC-EFB. Microbial analysis revealed that electrolysis could significantly change the microbial community and facilitate the proliferation of nitrogen-functional microbes, such as Thermomonas, Hydrogenophaga, Deinococcus, and Zoogloea. It is important to highlight that the hydrogen evolution reaction at the cathode area facilitated phosphorus removal in EC-EFB, thereby inhibiting phosphorus leaching. This study provides a promising and innovative technology for the purification of eutrophic water.

NIGT1 represses plant growth and mitigates phosphate starvation signaling to balance the growth response tradeoff in rice.

Inorganic phosphate (Pi) availability is an important factor which affects the growth and yield of crops, thus an appropriate and effective response to Pi fluctuation is critical. However, how crops orchestrate Pi signaling and growth under Pi starvation conditions to optimize the growth defense tradeoff remains unclear. Here we show that a Pi starvation-induced transcription factor NIGT1 (NITRATE-INDUCIBLE GARP-TYPE TRANSCRIPTIONAL REPRESSOR 1) controls plant growth and prevents a hyper-response to Pi starvation by directly repressing the expression of growth-related and Pi-signaling genes to achieve a balance between growth and response under a varying Pi environment. NIGT1 directly binds to the promoters of Pi starvation signaling marker genes, like IPS1, miR827, and SPX2, under Pi-deficient conditions to mitigate the Pi-starvation responsive (PSR). It also directly represses the expression of vacuolar Pi efflux transporter genes VPE1/2 to regulate plant Pi homeostasis. We further demonstrate that NIGT1 constrains shoot growth by repressing the expression of growth-related regulatory genes, including brassinolide signal transduction master regulator BZR1, cell division regulator CYCB1;1, and DNA replication regulator PSF3. Our findings reveal the function of NIGT1 in orchestrating plant growth and Pi starvation signaling, and also provide evidence that NIGT1 acts as a safeguard to avoid hyper-response during Pi starvation stress in rice.