Mechanisms of Cell Non-Autonomous Longevity Regulation

An organism’s ability to respond to stress is crucial for long-term survival. These stress responses are coordinated by distinct but overlapping pathways, many of which also regulate longevity across taxa. Our previous work identified a cell non-autonomous signaling pathway led by the hypoxia-inducible factor and resulting in induction of flavin-containing monooxygenase-2 (fmo-2) to promote health and longevity. Our current work identifies a distinct cell non-autonomous pathway downstream of dietary restriction (DR) that also relies on fmo-2 induction to promote health and longevity. We now find that these cell non-autonomous pathways can be mimicked by small molecule interventions that increase longevity by inducing fmo-2. Based on the commonalities of these pathways, we hypothesized that fmo-2, a classically annotated xenobiotic enzyme, might play a key endogenous role in responding to metabolic stress. Our resulting data, using metabolic profiling and further epistatic analysis, both support this hypothesis and link fmo-2’s mechanism to modifications in one-carbon metabolism (OCM), a key intermediate pathway consisting of the folate and methionine cycles. Using mathematical modeling and a labeled metabolomics approach, we were able to further identify the likely mechanism of fmo-2-mediated metabolic effects and connect them to both OCM and downstream components. We propose that fmo-2 is induced cell non-autonomously to modify systemic metabolism and longevity, and that fmo-2 is a key member of a conserved metabolic stress response.

Poplar aquaporin PIP1;1 promotes Arabidopsis growth and development

Background Root hydraulic conductance is primarily determined by the conductance of living tissues to radial water flow. Plasma membrane intrinsic proteins (PIPs) in root cortical cells are important for plants to take up water and are believed to be directly involved in cell growth. Results In this study, we found that constitutive overexpression of the poplar root-specific gene PtoPIP1;1 in Arabidopsis accelerated bolting and flowering. At the early stage of the developmental process, PtoPIP1;1 OE Arabidopsis exhibited faster cell growth in both leaves and roots. The turgor pressure of plants was correspondingly increased in PtoPIP1;1 OE Arabidopsis, and the water status was changed. At the same time, the expression levels of flowering-related genes (CRY1, CRY2 and FCA) and hub genes in the regulatory networks underlying floral timing (FT and SOC1) were significantly upregulated in OE plants, while the floral repressor FLC gene was significantly downregulated. Conclusions Taken together, the results of our study indicate that constitutive overexpression of PtoPIP1;1 in Arabidopsis accelerates bolting and flowering through faster cell growth in both the leaf and root at an early stage of the developmental process. The autonomous pathway of flowering regulation may be executed by monitoring developmental age. The increase in turgor and changes in water status with PtoPIP1;1 overexpression play a role in promoting cell growth.

Interferon Regulatory Factor 7 impairs cellular metabolism with age in adipose-derived stromal cells

Dysregulated immunity and widespread metabolic dysfunctions are the most relevant hallmarks of the passing time over the adult life and their combination at midlife is strongly related to increased vulnerability to diseases. However, their causal connection remains largely unclear. Combining multi-omics and functional analyses on adipose derived stromal cells established from young (1 month) and midlife (12 months) mice we show that the increase of Interferon Regulatory Factor 7 (IRF7) over the adult life drives major metabolic changes, which includes impaired mitochondrial function, altered amino acid biogenesis and reduced expression of genes involved in branched chain amino acid (BCAA) degradation. Our results draw a new paradigm of aging as the 'sterile' activation of a cell-autonomous pathway of self-defense and identify a crucial mediator of this pathway, IRF7, as driver of metabolic dysfunction with age.

Overexpression of the CmJAZ1-like gene delays flowering in Chrysanthemum morifolium

Chrysanthemum (Chrysanthemum morifolium) is one of the four major cut-flower plants worldwide and possesses both high ornamental value and cultural connotation. As most chrysanthemum varieties flower in autumn, it is costly to achieve annual production. JAZ genes in the TIFY family are core components of the jasmonic acid (JA) signaling pathway; in addition to playing a pivotal role in plant responses to defense, they are also widely implicated in regulating plant development processes. Here, we characterized the TIFY family gene CmJAZ1-like from the chrysanthemum cultivar ‘Jinba’. CmJAZ1-like localizes in the nucleus and has no transcriptional activity in yeast. Tissue expression pattern analysis indicated that CmJAZ1-like was most active in the root and shoot apex. Overexpressing CmJAZ1-like with Jas domain deletion in chrysanthemum resulted in late flowering. RNA-Seq analysis of the overexpression lines revealed some differentially expressed genes (DEGs) involved in flowering, such as the homologs of the flowering integrators FT and SOC1, an FUL homolog involved in flower meristem identity, AP2 domain-containing transcription factors, MADS box genes, and autonomous pathway-related genes. Based on KEGG pathway enrichment analysis, the differentially transcribed genes were enriched in carbohydrate metabolic and fatty acid-related pathways, which are notable for their role in flowering in plants. This study preliminarily verified the function of CmJAZ1-like in chrysanthemum flowering, and the results can be used in molecular breeding programs aimed at flowering time regulation of chrysanthemum.

CASP microdomain formation requires cross cell wall stabilization of domains between neighbors and non-cell autonomous action of LOTR1 cell wall protein

SummaryEfficient uptake of nutrients in both animal and plant cells requires tissue-spanning diffusion barriers separating inner tissues from the outer lumen/soil. However, we poorly understand how these contiguous three-dimensional superstructures are formed in plants. Here, we show that correct establishment of the plant Casparian Strip (CS) network requires neighbor communication. We show that positioning of Casparian Strip membrane domains (CSDs) is tightly coordinated between neighbors in wild-type and that restriction of domain formation involves the putative extracellular protease LOTR1. Impaired domain restriction in lotr1 is associated with disrupted CSDs and establishment of fully functional CSD at ectopic positions, forming “half strips”. LOTR1 is expressed in stele and needs to be expressed there. Endodermal expression, by contrast, cannot complement, while cortex expression causes a dominant-negative phenotype. Our findings establish LOTR1 as a crucial player in CSD positioning acting in a non-cell-autonomous pathway to restrict and coordinate CS positioning.

CYP720A1 function in roots is required for flowering time and systemic acquired resistance in the foliage of Arabidopsis

Systemic acquired resistance (SAR) is an inducible defense mechanism that systemically enhances resistance against pathogens in foliar tissues. SAR, which engages salicylic acid (SA) signaling, shares molecular components with the autonomous pathway, which is involved in controlling flowering time in Arabidopsis thaliana. FLOWERING LOCUS D (FLD) is one such autonomous pathway component that is required for flowering time and the systemic accumulation of SA during SAR. Here, we show that CYP720A1, a putative cytochrome P450 monoxygenase, controls FLD expression and is required for the timing of flowering and the manifestation of SAR. The delayed flowering time in the cyp720a1 mutant correlated with the elevated transcript level of the floral repressor FLC, while the SAR deficiency phenotype of the cyp720a1 mutant correlated with the inability to systemically accumulate SA. CYP720A1 transcript abundance in shoots is poor compared with roots. Reciprocal root–shoot grafting confirmed that CYP720A1 function in the roots is critical for flowering time and SAR. We therefore suggest that root to shoot communication involving a CYP720A1-dependent factor contributes to the timing of reproductive development and defense in the foliage.

Dehydroabietinal promotes flowering time and plant defense in Arabidopsis via the autonomous pathway genes FLOWERING LOCUS D, FVE, and RELATIVE OF EARLY FLOWERING 6

Abietane diterpenoids are tricyclic diterpenes whose biological functions in angiosperms are largely unknown. Here, we show that dehydroabietinal (DA) fosters transition from the vegetative phase to reproductive development in Arabidopsis thaliana by promoting flowering time. DA’s promotion of flowering time was mediated through up-regulation of the autonomous pathway genes FLOWERING LOCUS D (FLD), RELATIVE OF EARLY FLOWERING 6 (REF6), and FVE, which repress expression of FLOWERING LOCUS C (FLC), a negative regulator of the key floral integrator FLOWERING LOCUS T (FT). Our results further indicate that FLD, REF6, and FVE are also required for systemic acquired resistance (SAR), an inducible defense mechanism that is also activated by DA. However, unlike flowering time, FT was not required for DA-induced SAR. Conversely, salicylic acid, which is essential for the manifestation of SAR, was not required for the DA-promoted flowering time. Thus, although the autonomous pathway genes FLD, REF6, and FVE are involved in SAR and flowering time, these biological processes are not interdependent. We suggest that SAR and flowering time signaling pathways bifurcate at a step downstream of FLD, REF6, and FVE, with an FLC-dependent arm controlling flowering time, and an FLC-independent pathway controlling SAR.

Single Cell RNA Profiling Reveals Adipocyte to Macrophage Signaling Sufficient to Enhance Thermogenesis

ABSTRACTThe “browning” of inguinal white adipose tissue (iWAT) through increased abundance of thermogenic beige/brite adipocytes is induced by cold exposure and many other perturbations in association with beneficial systemic metabolic effects. Adipose browning is reported to require activation of sympathetic nerve fibers (SNF), aided by alternately activated macrophages within iWAT. Here we demonstrate the first example of a non-cell autonomous pathway for iWAT browning that is fully independent of SNF activity. Thus, the strong induction of thermogenic adipocytes prompted by deletion of adipocyte fatty acid synthase (iAdFASNKO mice) was unaffected by denervation or the deletion of SNF modulator Neuregulin-4. However, browning of iWAT in iAdFASNKO mice does require adipocyte cAMP/protein kinase A signaling, as it was blocked in adipocyte- selective Fasn/Gsα double KO mice. Single-cell transcriptomic analysis of iAdFASNKO mouse adipose stromal cells revealed increased macrophages displaying gene expression signatures of the alternately activated type. Mechanistically, depletion of such phagocytic immune cells in iAdFASNKO mice fully abrogated appearance of thermogenic adipocytes in iWAT. Altogether, these findings reveal an unexpected pathway of cAMP/PKA-dependent iWAT browning that is initiated by adipocyte signals and caused by macrophage-like cells independent of sympathetic neuron involvement.

TRANSPARENT TESTA GLABRA 1 participates in flowering time regulation in Arabidopsis thaliana

Pleiotropic regulatory factors mediate concerted responses of the plant’s trait network to endogenous and exogenous cues. TRANSPARENT TESTA GLABRA 1 (TTG1) is such a factor that has been predominantly described as a regulator of early developmental traits. Although its closest homologs LIGHT-REGULATED WD1 (LWD1) and LWD2 affect photoperiodic flowering, a role of TTG1 in flowering time regulation has not been reported. Here we reveal that TTG1 is a regulator of flowering time in Arabidopsis thaliana and changes transcript levels of different targets within the flowering time regulatory pathway. TTG1 mutants flower early and TTG1 overexpression lines flower late at long-day conditions. Consistently, TTG1 can suppress the transcript levels of the floral integrators FLOWERING LOCUS T and SUPPRESSOR OF OVEREXPRESSION OF CO1 and can act as an activator of circadian clock components. Moreover, TTG1 might form feedback loops at the protein level. The TTG1 protein interacts with PSEUDO RESPONSE REGULATOR (PRR)s and basic HELIX-LOOP-HELIX 92 (bHLH92) in yeast. In planta, the respective pairs exhibit interesting patterns of localization including a recruitment of TTG1 by PRR5 to subnuclear foci. This mechanism proposes additional layers of regulation by TTG1 and might aid to specify the function of bHLH92. Within another branch of the pathway, TTG1 can elevate FLOWERING LOCUS C (FLC) transcript levels. FLC mediates signals from the vernalization, ambient temperature and autonomous pathway and the circadian clock is pivotal for the plant to synchronize with diurnal cycles of environmental stimuli like light and temperature. Our results suggest an unexpected positioning of TTG1 upstream of FLC and upstream of the circadian clock. In this light, this points to an adaptive value of the role of TTG1 in respect to flowering time regulation.