Summary of Study ST004039
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002531. The data can be accessed directly via it's Project DOI: 10.21228/M8GR97 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST004039 |
| Study Title | Soma to neuron communication links stress adaptation to stress avoidance behavior |
| Study Summary | In multicellular organisms, signaling from the nervous system to the peripheral tissues can activate physiological responses to stress. Here, we show that inter-tissue stress communication can also function in reverse, i.e. from the peripheral tissue to the nervous system. osm-8 mutants, which activate the osmotic stress response in the C. elegans skin, also exhibit defective osmotic avoidance behavior, which is regulated by the ASH neuronal avoidance circuit. osm-8 osmotic avoidance behavior is completely suppressed by mutation of the Patched/NPC1 homolog ptr-23. The function of osm-8 and ptr-23 in the hypodermal epithelial cells is both necessary and sufficient for directing neuronal osmotic avoidance behavior. Endogenously tagged alleles of osm-8 and ptr-23 co-localize exclusively in the hypodermal lysosomes. Unbiased lipidomic analysis shows that osm-8 leads to a ptr-23-dependent elevation of the lysosome specific lipid bis(monoacylglycero)phosphate (BMP) and expansion of the pool of hypodermal lysosomes. Just as genetic activation of the osmotic stress response by loss of osm-8 in the hypodermis causes an Osm phenotype, acute physiological exposure to osmotic stress also confers a reversible Osm phenotype. Behavioral plasticity requires glycerol production, as mutations in the glycerol biosynthetic enzymes gpdh-1 and gpdh-2 are defective in acquired Osm behavior. While the osm-8 induced Osm behavior requires ptr-23, physiologically induced Osm behavior does not. Instead, both genetic and physiologically induced Osm phenotypes require the unusual non-neuronal lysosomal V-ATPase subunit vha-5, which is also critical for organismal osmotic stress survival. Together, these data reveal that genetic or physiological activation of stress signaling from the skin elicits lysosome-associated signals that modulate the function of a sensory neuron circuit. Such ‘body-brain’ interoceptive communication may allow organisms to better match neuronal decision-making with organismal physiological state. |
| Institute | University of Pittsburgh |
| Department | Pediatrics and Cell Biology |
| Laboratory | Lamitina Lab |
| Last Name | Lamitina |
| First Name | Todd |
| Address | 4401 Penn Ave, Rangos 7122 |
| stl52@pitt.edu | |
| Phone | 12674390330 |
| Submit Date | 2025-05-19 |
| Num Groups | 3 |
| Total Subjects | 18 |
| Publications | https://doi.org/10.1101/2025.05.07.652728 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzXML |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-07-31 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002531 |
| Project DOI: | doi: 10.21228/M8GR97 |
| Project Title: | Soma to neuron communication links stress adaptation to stress avoidance behavior |
| Project Summary: | In multicellular organisms, signaling from the nervous system to the peripheral tissues can activate physiological responses to stress. Here, we show that inter-tissue stress communication can also function in reverse, i.e. from the peripheral tissue to the nervous system. osm-8 mutants, which activate the osmotic stress response in the C. elegans skin, also exhibit defective osmotic avoidance behavior, which is regulated by the ASH neuronal avoidance circuit. osm-8 osmotic avoidance behavior is completely suppressed by mutation of the Patched/NPC1 homolog ptr-23. The function of osm-8 and ptr-23 in the hypodermal epithelial cells is both necessary and sufficient for directing neuronal osmotic avoidance behavior. Endogenously tagged alleles of osm-8 and ptr-23 co-localize exclusively in the hypodermal lysosomes. Unbiased lipidomic analysis shows that osm-8 leads to a ptr-23-dependent elevation of the lysosome specific lipid bis(monoacylglycero)phosphate (BMP) and expansion of the pool of hypodermal lysosomes. Just as genetic activation of the osmotic stress response by loss of osm-8 in the hypodermis causes an Osm phenotype, acute physiological exposure to osmotic stress also confers a reversible Osm phenotype. Behavioral plasticity requires glycerol production, as mutations in the glycerol biosynthetic enzymes gpdh-1 and gpdh-2 are defective in acquired Osm behavior. While the osm-8 induced Osm behavior requires ptr-23, physiologically induced Osm behavior does not. Instead, both genetic and physiologically induced Osm phenotypes require the unusual non-neuronal lysosomal V-ATPase subunit vha-5, which is also critical for organismal osmotic stress survival. Together, these data reveal that genetic or physiological activation of stress signaling from the skin elicits lysosome-associated signals that modulate the function of a sensory neuron circuit. Such ‘body-brain’ interoceptive communication may allow organisms to better match neuronal decision-making with organismal physiological state. |
| Institute: | University of Pittsburgh |
| Department: | Pediatrics and Cell Biology |
| Laboratory: | Lamitina Lab |
| Last Name: | Lamitina |
| First Name: | Todd |
| Address: | Childrens Hospital of Pittsburgh |
| Email: | stl52@pitt.edu |
| Phone: | 267-439-0330 |
| Funding Source: | NIH R01GM135577; NIH S10OD023402 |
Subject:
| Subject ID: | SU004185 |
| Subject Type: | Invertebrate |
| Subject Species: | Caenorhabditis elegans |
| Taxonomy ID: | 6239 |
| Genotype Strain: | Wild type, osm-8(dr170), osm-8(dr170); ptr-23(dr180) |
| Age Or Age Range: | Day 1 adults |
| Gender: | Hermaphrodite |
Factors:
Subject type: Invertebrate; Subject species: Caenorhabditis elegans (Factor headings shown in green)
| mb_sample_id | local_sample_id | Sample source | Genotype |
|---|---|---|---|
| SA467029 | dr170_1 | C.Elegans tissue | osm-8(dr170) |
| SA467030 | dr170_2 | C.Elegans tissue | osm-8(dr170) |
| SA467031 | dr170_3 | C.Elegans tissue | osm-8(dr170) |
| SA467032 | dr170_5 | C.Elegans tissue | osm-8(dr170) |
| SA467033 | dr170_6 | C.Elegans tissue | osm-8(dr170) |
| SA467034 | dr170_4 | C.Elegans tissue | osm-8(dr170) |
| SA467035 | dr170 dr180_1 | C.Elegans tissue | osm-8(dr170) ptr-23(dr180) |
| SA467036 | dr170 dr180_2 | C.Elegans tissue | osm-8(dr170) ptr-23(dr180) |
| SA467037 | dr170 dr180_3 | C.Elegans tissue | osm-8(dr170) ptr-23(dr180) |
| SA467038 | dr170 dr180_4 | C.Elegans tissue | osm-8(dr170) ptr-23(dr180) |
| SA467039 | dr170 dr180_5 | C.Elegans tissue | osm-8(dr170) ptr-23(dr180) |
| SA467040 | dr170 dr180_6 | C.Elegans tissue | osm-8(dr170) ptr-23(dr180) |
| SA467023 | N2_6 | C.Elegans tissue | Wild type |
| SA467024 | N2_2 | C.Elegans tissue | Wild type |
| SA467025 | N2_1 | C.Elegans tissue | Wild type |
| SA467026 | N2_5 | C.Elegans tissue | Wild type |
| SA467027 | N2_4 | C.Elegans tissue | Wild type |
| SA467028 | N2_3 | C.Elegans tissue | Wild type |
| Showing results 1 to 18 of 18 |
Collection:
| Collection ID: | CO004178 |
| Collection Summary: | For each replicate, N2, osm-8(dr170), and osm-8(dr170); ptr-23(dr180) animals were seeded on 3x15 cm NGM plate with a lawn of OP50 as starved L1s. Animals were grown at 20ºC until animals were day 1 adults. We collected a total of six replicates for each genotype for analysis. Worms were washed off plates using M9 buffer, pelleted in a swinging bucket centrifuge at 2,000xg for 1 minute, and then washed three times. Worm pellets were resuspended in 10ml of M9 buffer and incubated at 20ºC with rocking for 15 minutes to evacuate OP50 bacteria from the intestine. Worms were pelleted and the density of worms per microliter was calculated for each strain. For each sample, ~5,000 worms were pipetted into 2.0ml tubes containing a MP Bio Matrix A (garnet/ceramic sphere) and frozen at -80ºC prior to processing. |
| Sample Type: | Worms |
| Storage Conditions: | -80℃ |
| Collection Vials: | 2.0ml tubes |
| Additives: | MP Bio Matrix A |
Treatment:
| Treatment ID: | TR004194 |
| Treatment Summary: | No treatment. All strains were grown under identical isotonic plate conditions (51mM NaCl NGM plates). The only variable was genotype. |
Sample Preparation:
| Sampleprep ID: | SP004191 |
| Sampleprep Summary: | Metabolic quenching, lysis, and lipid extraction was performed by adding 0.5mL ice cold phosphate buffered saline. Samples were homogenized in MP Biomatrix A tubes at 60 Hz for 1 minute. Uncleared supernatant (400 µL) was transferred to a clean glass tube containing 10 µL of LipidSplash, deuterated internal standards (Avanti Polar Lipids. Alabaster, AL) and subjected to Folch extraction. Samples were rested on ice for 10 minutes before phase separation via centrifugation at 2500 x g for 15 minutes. The organic phase (0.7 mL) was transferred to a clean glass vial and dried to completion under N2. Samples were resuspended in 100 µL of 1:1 acetonitrile:isopropanol and 3µL was injected for online LC-HRMS analysis. |
Chromatography:
| Chromatography ID: | CH005074 |
| Chromatography Summary: | Briefly, samples were injected via a Thermo Vanquish UHPLC and separated over a reversed phase Thermo Accucore C-18 column (2.1×100mm, 5μm particle size) maintained at 55°C. For the 30 minute LC gradient, the mobile phase consisted of the following: solvent A (50:50 H2O:ACN 10 mM ammonium acetate/0.1% acetic acid) and solvent B (90:10 IPA:ACN 10 mM ammonium acetate/0.1% acetic acid). The gradient started at 30% B and increased to 43%B over 2 minutes followed by an increase to 55%B in 0.1 minute. The organic increased to 65%B over the next 10 minutes, followed by an increase to 85%B over 6 minutes. For column washing the gradient increased to 100%B over 2 minutes and was held for 5 minutes followed by 5 minutes of equilibration at 30%B. |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Thermo Accucore Vanquish C18+ UHPLC (100 x 2.1mm, 1.5um) |
| Column Temperature: | 55 |
| Flow Gradient: | 30% B and increased to 43%B over 2 minutes followed by an increase to 55%B in 0.1 minute. The organic increased to 65%B over the next 10 minutes, followed by an increase to 85%B over 6 minutes. For column washing the gradient increased to 100%B over 2 minutes and was held for 5 minutes followed by 5 minutes of equilibration at 30%B |
| Flow Rate: | 0.260mL/min |
| Solvent A: | 50% water/50% acetonitrile; 10 mM ammonium acetate; 0.1% acetic acid |
| Solvent B: | 90% isopropanol/10% acetonitrile; 10 mM ammonium acetate; 0.1% acetic acid |
| Chromatography Type: | Reversed phase |
Analysis:
| Analysis ID: | AN006677 |
| Analysis Type: | MS |
| Chromatography ID: | CH005074 |
| Num Factors: | 3 |
| Num Metabolites: | 1527 |
| Units: | Normalized Peak area |
| Analysis ID: | AN006678 |
| Analysis Type: | MS |
| Chromatography ID: | CH005074 |
| Num Factors: | 3 |
| Num Metabolites: | 1181 |
| Units: | Normalized Peak area |
