Summary of Study ST002878

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 PR001761. The data can be accessed directly via it's Project DOI: 10.21228/M83139 This work is supported by NIH grant, U2C- DK119886.

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Study IDST002878
Study TitleAtlas of fetal metabolism during mid-to-late gestation and diabetic pregnancy. Dynamic Labelling experiment.
Study SummaryMounting evidence supports an instructive role for metabolism in stem cell fate decisions. However, much is yet unknown about how fetal metabolism changes during mammalian development and how altered maternal metabolism shapes fetal metabolism. Here, we present a descriptive atlas of in vivo fetal murine metabolism during mid-to-late gestation in normal and diabetic pregnancy. Using 13C-glucose and LC-MS, we profiled the metabolism of fetal brains, hearts, livers, and placentas harvested from pregnant dams between embryonic days (E)10.5 and 18.5. Comparative analysis of our large metabolomics dataset revealed metabolic features specific to fetal tissues developed under a hyperglycemic environment as well as metabolic signatures that may denote developmental transitions during euglycemic development. We observed sorbitol accumulation in fetal tissues and altered neurotransmitter levels in fetal brains isolated from dams with maternal hyperglycemia. Tracing 13C-glucose revealed disparate nutrient sourcing in fetuses depending on maternal glycemic states. Regardless of glycemic state, histidine-derived metabolites accumulated during late development in fetal tissues and maternal plasma. Our rich dataset presents a comprehensive overview of in vivo fetal tissue metabolism and alterations occurring as a result of maternal hyperglycemia.
Institute
University of California, Los Angeles
DepartmentBiological Chemistry
LaboratoryHeather Christofk
Last NameMatulionis
First NameNedas
Address615 Charles E Young Drive South Los Angeles, CA, 90095
Emailnmatulionis@mednet.ucla.edu
Phone3102060163
Submit Date2023-09-25
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2023-12-08
Release Version1
Nedas Matulionis Nedas Matulionis
https://dx.doi.org/10.21228/M83139
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001761
Project DOI:doi: 10.21228/M83139
Project Title:Atlas of fetal metabolism during mid-to-late gestation and diabetic pregnancy
Project Summary:Mounting evidence supports an instructive role for metabolism in stem cell fate decisions. However, much is yet unknown about how fetal metabolism changes during mammalian development and how altered maternal metabolism shapes fetal metabolism. Here, we present a descriptive atlas of in vivo fetal murine metabolism during mid-to-late gestation in normal and diabetic pregnancy. Using 13C-glucose and LC-MS, we profiled the metabolism of fetal brains, hearts, livers, and placentas harvested from pregnant dams between embryonic days (E)10.5 and 18.5. Comparative analysis of our large metabolomics dataset revealed metabolic features specific to fetal tissues developed under a hyperglycemic environment as well as metabolic signatures that may denote developmental transitions during euglycemic development. We observed sorbitol accumulation in fetal tissues and altered neurotransmitter levels in fetal brains isolated from dams with maternal hyperglycemia. Tracing 13C-glucose revealed disparate nutrient sourcing in fetuses depending on maternal glycemic states. Regardless of glycemic state, histidine-derived metabolites accumulated during late development in fetal tissues and maternal plasma. Our rich dataset presents a comprehensive overview of in vivo fetal tissue metabolism and alterations occurring as a result of maternal hyperglycemia.
Institute:University of California, Los Angeles
Department:Biological Chemistry
Laboratory:Heather Christofk
Last Name:Matulionis
First Name:Nedas
Address:615 Charles E Young Drive South Los Angeles, CA, 90095
Email:nmatulionis@mednet.ucla.edu
Phone:3102060163

Subject:

Subject ID:SU002991
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Genotype U13C Glucose Labelling Timepoint
SA314499AK15-D8-S-01Akita 0 minutes
SA314500AK15-D4-S-01Akita 0 minutes
SA314501AK15-D10-S-01Akita 0 minutes
SA314502AK15-D9-H-01Akita 0 minutes
SA314503AK15-D9-S-01Akita 0 minutes
SA314504AK15-D9-B-01Akita 0 minutes
SA314505AK15-D9-L-01Akita 0 minutes
SA314506AK15-D9-P-01Akita 0 minutes
SA314507AK15-D4-P-01Akita 0 minutes
SA314508AK15-D9-H-03Akita 1 hour
SA314509AK15-D4-P-03Akita 1 hour
SA314510AK15-D9-P-03Akita 1 hour
SA314511AK15-D9-L-03Akita 1 hour
SA314512AK15-D4-S-03Akita 1 hour
SA314513AK15-D9-S-03Akita 1 hour
SA314514AK15-D8-S-03Akita 1 hour
SA314515AK15-D10-S-03Akita 1 hour
SA314516AK15-D9-B-03Akita 1 hour
SA314517AK15-D9-P-04Akita 2 hours
SA314518AK15-D9-S-04Akita 2 hours
SA314519AK15-D10-S-04Akita 2 hours
SA314520AK15-D9-H-04Akita 2 hours
SA314521AK15-D4-P-04Akita 2 hours
SA314522AK15-D9-L-04Akita 2 hours
SA314523AK15-D4-S-04Akita 2 hours
SA314524AK15-D9-B-04Akita 2 hours
SA314525AK15-D8-S-04Akita 2 hours
SA314535AK15-D4-P-02Akita 30 minutes
SA314536AK15-D9-B-02Akita 30 minutes
SA314537AK15-D10-S-02Akita 30 minutes
SA314538AK15-D9-L-02Akita 30 minutes
SA314539AK15-D9-P-02Akita 30 minutes
SA314540AK15-D4-S-02Akita 30 minutes
SA314541AK15-D8-S-02Akita 30 minutes
SA314542AK15-D9-H-02Akita 30 minutes
SA314543AK15-D9-S-02Akita 30 minutes
SA314526AK15-D9-H-05Akita 3 hours
SA314527AK15-D8-S-05Akita 3 hours
SA314528AK15-D4-S-05Akita 3 hours
SA314529AK15-D10-S-05Akita 3 hours
SA314530AK15-D9-P-05Akita 3 hours
SA314531AK15-D4-P-05Akita 3 hours
SA314532AK15-D9-B-05Akita 3 hours
SA314533AK15-D9-S-05Akita 3 hours
SA314534AK15-D9-L-05Akita 3 hours
SA314544AK15-D9-B-06Akita 4 hours
SA314545AK15-D9-H-06Akita 4 hours
SA314546AK15-D9-L-06Akita 4 hours
SA314547AK15-D9-S-06Akita 4 hours
SA314548AK15-D9-P-06Akita 4 hours
SA314549AK15-D4-P-06Akita 4 hours
SA314550AK15-D8-S-06Akita 4 hours
SA314551AK15-D4-S-06Akita 4 hours
SA314552WT15-D4-L-01Wild Type 0 minutes
SA314553WT15-D6-B-01Wild Type 0 minutes
SA314554WT15-D7-S-01Wild Type 0 minutes
SA314555WT15-D3-S-01Wild Type 0 minutes
SA314556WT15-D7-B-01Wild Type 0 minutes
SA314557WT15-D3-L-01Wild Type 0 minutes
SA314558WT15-D6-L-01Wild Type 0 minutes
SA314559WT15-D4-S-01Wild Type 0 minutes
SA314560WT15-D4-B-01Wild Type 0 minutes
SA314561WT15-D7-P-01Wild Type 0 minutes
SA314562WT15-D3-H-01Wild Type 0 minutes
SA314563WT15-D4-H-01Wild Type 0 minutes
SA314564WT15-D6-S-01Wild Type 0 minutes
SA314565WT15-D7-L-01Wild Type 0 minutes
SA314566WT15-D6-H-01Wild Type 0 minutes
SA314567WT15-D6-P-01Wild Type 0 minutes
SA314568WT15-D7-H-01Wild Type 0 minutes
SA314569WT15-D3-B-01Wild Type 0 minutes
SA314570WT15-D4-P-01Wild Type 0 minutes
SA314571WT15-D3-P-01Wild Type 0 minutes
SA314572WT15-D3-S-03Wild Type 1 hour
SA314573WT15-D7-S-03Wild Type 1 hour
SA314574WT15-D4-S-03Wild Type 1 hour
SA314575WT15-D4-P-03Wild Type 1 hour
SA314576WT15-D3-P-03Wild Type 1 hour
SA314577WT15-D6-P-03Wild Type 1 hour
SA314578WT15-D7-P-03Wild Type 1 hour
SA314579WT15-D6-S-03Wild Type 1 hour
SA314580WT15-D7-L-03Wild Type 1 hour
SA314581WT15-D4-H-03Wild Type 1 hour
SA314582WT15-D7-B-03Wild Type 1 hour
SA314583WT15-D3-L-03Wild Type 1 hour
SA314584WT15-D6-H-03Wild Type 1 hour
SA314585WT15-D4-L-03Wild Type 1 hour
SA314586WT15-D3-B-03Wild Type 1 hour
SA314587WT15-D6-B-03Wild Type 1 hour
SA314588WT15-D4-B-03Wild Type 1 hour
SA314589WT15-D6-L-03Wild Type 1 hour
SA314590WT15-D3-H-03Wild Type 1 hour
SA314591WT15-D7-H-03Wild Type 1 hour
SA314592WT15-D4-P-04Wild Type 2 hours
SA314593WT15-D7-B-04Wild Type 2 hours
SA314594WT15-D3-H-04Wild Type 2 hours
SA314595WT15-D6-P-04Wild Type 2 hours
SA314596WT15-D3-P-04Wild Type 2 hours
SA314597WT15-D7-H-04Wild Type 2 hours
SA314598WT15-D4-H-04Wild Type 2 hours
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Collection:

Collection ID:CO002984
Collection Summary:Healthy wildtype and Akita dams were set up for mating. The following morning, females displaying vaginal plugs were identified as pregnant, recorded as embryonic day (E) 0.5 and moved to a new cage until the appropriate embryonic day to be interrogated.
Sample Type:Embryo

Treatment:

Treatment ID:TR003000
Treatment Summary:Pregnant mice were placed under a maintained plane of isoflurane anesthesia (2.5%). Retro-orbital blood draw for time zero was performed followed by opening a small incision to the lower abdomen of the pregnant mouse to expose a single conceptus for fetal tissue harvesting. Immediately after the first blood draw and fetus collection, a tail vein catheter was placed and bolus (4 µL/gBW) was administered followed by continuous infusion (0.085ul/gBW/min). A single conceptus, accessed via the initial small incision, was harvested at multiple time points during infusion of the nutrient tracer (13C glucose). Retro-orbital blood draws (<20 ul) were taken throughout the infusion to monitor tracer enrichment in maternal blood. Timepoints for harvesting after time zero were: 30 minutes, 1 hour, 2 hours, 3 hours, and 4 hours.

Sample Preparation:

Sampleprep ID:SP002997
Sampleprep Summary:Fetal tissue extraction: Following infusion, mice were euthanized and blood was collected via heart puncture. Fetal tissues (placenta, brain, liver, and heart) were dissected in ice-cold sterile PBS. Immediately after dissection, weight was recorded and fetal tissue was placed in a pre-filled bead mill tube containing metal beads and 500 µL of methanol:water (80:20) solution kept cold on dry ice. Fetal tissues were homogenized using a Fisherbrand™ Bead Mill Homogenizer. Samples were spun twice at >17,000 g (4 °C) to remove precipitated cell material (protein/DNA). Supernatants were collected, transferred to a clean tube, and evaporated using a Nitrogen evaporator (Organomation). Evaporated samples were stored at -80 °C. Pellets containing protein/DNA were dried on a heat block (55 °C) and stored at -80 °C. Serum extraction: Collected blood was centrifuged at 5,000g to collect serum. Serum was snap frozen in liquid nitrogen and stored until extraction. For metabolite extraction 5 µL serum was mixed with 500 µL 100% MeOH (-80 °C). Samples were centrifuged for 10 min at >17,000 g (4 °C) and 450 µL of each sample evaporated using a Nitrogen evaporator (Organomation). Evaporated samples were stored at -80 °C.
Processing Storage Conditions:On ice
Extract Storage:-80℃

Combined analysis:

Analysis ID AN004715 AN004716
Analysis type MS MS
Chromatography type HILIC HILIC
Chromatography system Thermo Vanquish Thermo Vanquish
Column SeQuant ZIC-HILIC (150 x 2.1mm,5um) SeQuant ZIC-HILIC (150 x 2.1mm,5um)
MS Type ESI ESI
MS instrument type Orbitrap Orbitrap
MS instrument name Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap
Ion Mode POSITIVE NEGATIVE
Units Peak Area Peak Area

Chromatography:

Chromatography ID:CH003551
Chromatography Summary:Dried metabolites were reconstituted in 100 µL of a 50% acetonitrile (ACN) 50% dH20 solution. Samples were vortexed and spun down for 10 min at 17,000g. 70 µL of the supernatant was then transferred to HPLC glass vials. 10 µL of these metabolite solutions were injected per analysis. Samples were run on a Vanquish (Thermo Scientific) UHPLC system with mobile phase A (20mM ammonium carbonate, pH 9.7) and mobile phase B (100% ACN) at a flow rate of 150 µL/min on a SeQuant ZIC-pHILIC Polymeric column (2.1 × 150 mm 5 μm, EMD Millipore) at 35°C. Separation was achieved with a linear gradient from 20% A to 80% A in 20 min followed by a linear gradient from 80% A to 20% A from 20 min to 20.5 min. 20% A was then held from 20.5 min to 28 min.
Instrument Name:Thermo Vanquish
Column Name:SeQuant ZIC-HILIC (150 x 2.1mm,5um)
Column Temperature:35°C
Flow Gradient:Separation was achieved with a linear gradient from 20% A to 80% A in 20 min followed by a linear gradient from 80% A to 20% A from 20 min to 20.5 min. 20% A was then held from 20.5 min to 28 min.
Flow Rate:150 µL/min
Solvent A:100% water; 20 mM ammonium carbonate, pH 9.7
Solvent B:100% acetonitrile
Chromatography Type:HILIC

MS:

MS ID:MS004461
Analysis ID:AN004715
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:The UHPLC was coupled to a Q-Exactive (Thermo Scientific) mass analyzer running in polarity switching mode with spray-voltage=3.2kV, sheath-gas=40, aux-gas=15, sweep-gas=1, aux-gas-temp=350°C, and capillary-temp=275°C. For both polarities mass scan settings were kept at full-scan-range = (70-1000), ms1-resolution=70,000, max-injection-time=250ms, and AGC-target=1E6. MS2 data was also collected from the top three most abundant singly-charged ions in each scan with normalized-collision-energy=35. Each of the resulting “.RAW” files was then centroided and converted into two “.mzXML” files (one for positive scans and one for negative scans) using msconvert from ProteoWizard. These “.mzXML” files were imported into the MZmine 2 software package. Ion chromatograms were generated from MS1 spectra via the built-in Automated Data Analysis Pipeline (ADAP) chromatogram module and peaks were detected via the ADAP wavelets algorithm. Peaks were aligned across all samples via the Random sample consensus aligner module, gap-filled, and assigned identities using an exact mass MS1(+/-15ppm) and retention time RT (+/-0.5min) search of our in-house MS1-RT database. Peak boundaries and identifications were then further refined by manual curation. Peaks were quantified by area under the curve integration and exported as CSV files. If stable isotope tracing was used in the experiment, the peak areas were additionally processed via the R package AccuCor 2 to correct for natural isotope abundance. Peak areas for each sample were normalized by the measured area of the internal standard trifluoromethanesulfonate (present in the extraction buffer) and by the number of cells present in the extracted well.
Ion Mode:POSITIVE
  
MS ID:MS004462
Analysis ID:AN004716
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:The UHPLC was coupled to a Q-Exactive (Thermo Scientific) mass analyzer running in polarity switching mode with spray-voltage=3.2kV, sheath-gas=40, aux-gas=15, sweep-gas=1, aux-gas-temp=350°C, and capillary-temp=275°C. For both polarities mass scan settings were kept at full-scan-range = (70-1000), ms1-resolution=70,000, max-injection-time=250ms, and AGC-target=1E6. MS2 data was also collected from the top three most abundant singly-charged ions in each scan with normalized-collision-energy=35. Each of the resulting “.RAW” files was then centroided and converted into two “.mzXML” files (one for positive scans and one for negative scans) using msconvert from ProteoWizard. These “.mzXML” files were imported into the MZmine 2 software package. Ion chromatograms were generated from MS1 spectra via the built-in Automated Data Analysis Pipeline (ADAP) chromatogram module and peaks were detected via the ADAP wavelets algorithm. Peaks were aligned across all samples via the Random sample consensus aligner module, gap-filled, and assigned identities using an exact mass MS1(+/-15ppm) and retention time RT (+/-0.5min) search of our in-house MS1-RT database. Peak boundaries and identifications were then further refined by manual curation. Peaks were quantified by area under the curve integration and exported as CSV files. If stable isotope tracing was used in the experiment, the peak areas were additionally processed via the R package AccuCor 2 to correct for natural isotope abundance. Peak areas for each sample were normalized by the measured area of the internal standard trifluoromethanesulfonate (present in the extraction buffer) and by the number of cells present in the extracted well.
Ion Mode:NEGATIVE
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