Summary of Study ST003747
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 PR002333. The data can be accessed directly via it's Project DOI: 10.21228/M82K0C 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 | ST003747 |
| Study Title | Phosphatidylinositol remodeling by lysophospholipid acyltransferase 11 ensures embryonic radial glial cell integrity - part 1 |
| Study Summary | Since fragmentation of the Golgi apparatus is associated with defects in phosphoinositide (PIP) metabolisms, we measured PI in E11.5-E13.5 cortices by using liquid chromatography-mass spectrometry (LC-MS). In Mboat7 KO mice, PI with arachidonic acid (38:4 PI), which is the major species in Mboat7 heterozygous mice, significantly decreased, and instead, PI with monounsaturated fatty acid (34:1, 34:2, 36:1, 36:2 PI) and PI with docosapentaenoic acid (DPA) or docosahexaenoic acid (DHA) (38:6, 40:5, 40:6, 40:7 PI) increased. On the other hand, the composition of molecular species of phosphatidylserine (PS), phosphatidylcholine (PC), and phosphatidylethanolamine (PE) showed little or no change in the cortices of E11.5-E13.5 Mboat7 KO mice compared with Mboat7 heterozygous mice. |
| Institute | University of Tokyo |
| Last Name | Kono |
| First Name | Nozomu |
| Address | Hongo 7-3-1, Bunkyo-ku, Tokyo 113-033 JAPAN |
| nozomu@mol.f.u-tokyo.ac.jp | |
| Phone | 81-3-5841-4723 |
| Submit Date | 2025-01-25 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-03-14 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002333 |
| Project DOI: | doi: 10.21228/M82K0C |
| Project Title: | Phosphatidylinositol remodeling by lysophospholipid acyltransferase 11 ensures embryonic radial glial cell integrity |
| Project Summary: | Arachidonic acid, a vital polyunsaturated fatty acid in brain development, is enriched in phosphatidylinositol (PI). The arachidonic acyl chain in PI is introduced by lysophospholipid acyltransferase 11 (LPLAT11)/membrane-bound O-acyltransferase 7 (MBOAT7), the loss of which causes microcephaly in humans and mice. Here, we show that LPLAT11 deficiency impaired indirect neurogenesis in the developing neocortex, resulting in fewer layer II-V neurons. LPLAT11-deficient radial glial cells had defects in differentiation into intermediate progenitor cells and increased apoptosis. Prior to these anomalies, LPLAT11 deficiency caused a rounding of the Golgi apparatus, accompanied by impaired apical trafficking of E-cadherin, and deregulated apical detachment. Moreover, impaired PI acyl chain remodeling led to a decreased amount of PI(4,5)P2, leading to Golgi apparatus rounding. Thus, these results clarify the underlying mechanism of microcephaly by LPLAT11 deficiency and highlight the critical role of arachidonic acid in PI in the integrity of radial glial cells. |
| Institute: | University of Tokyo |
| Department: | Graduate School of Pharmaceutical Sciences |
| Laboratory: | Department of Health Chemistry |
| Last Name: | Kono |
| First Name: | Nozomu |
| Address: | Hongo 7-3-1,, Bunyo-ku, Tokyo, 113-0033, Japan |
| Email: | nozomu@mol.f.u-tokyo.ac.jp |
| Phone: | 81-3-5841-4723 |
Subject:
| Subject ID: | SU003880 |
| 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 | Sample source | Gestational ages | Genotype |
|---|---|---|---|---|
| SA408239 | E11.5_Het_1_PS_PI | brain cortex | E11.5 | Mboat7+/- |
| SA408240 | E11.5_Het_2_PC_PE | brain cortex | E11.5 | Mboat7+/- |
| SA408241 | E11.5_Het_4_PS_PI | brain cortex | E11.5 | Mboat7+/- |
| SA408242 | E11.5_Het_3_PS_PI | brain cortex | E11.5 | Mboat7+/- |
| SA408243 | E11.5_Het_2_PS_PI | brain cortex | E11.5 | Mboat7+/- |
| SA408244 | E11.5_Het_1_PC_PE | brain cortex | E11.5 | Mboat7+/- |
| SA408245 | E11.5_Het_3_PC_PE | brain cortex | E11.5 | Mboat7+/- |
| SA408246 | E11.5_Het_4_PC_PE | brain cortex | E11.5 | Mboat7+/- |
| SA408247 | E11.5_KO_4_PC_PE | brain cortex | E11.5 | Mboat7-/- |
| SA408248 | E11.5_KO_3_PC_PE | brain cortex | E11.5 | Mboat7-/- |
| SA408249 | E11.5_KO_2_PC_PE | brain cortex | E11.5 | Mboat7-/- |
| SA408250 | E11.5_KO_1_PC_PE | brain cortex | E11.5 | Mboat7-/- |
| SA408251 | E11.5_KO_1_PS_PI | brain cortex | E11.5 | Mboat7-/- |
| SA408252 | E11.5_KO_2_PS_PI | brain cortex | E11.5 | Mboat7-/- |
| SA408253 | E11.5_KO_3_PS_PI | brain cortex | E11.5 | Mboat7-/- |
| SA408254 | E11.5_KO_4_PS_PI | brain cortex | E11.5 | Mboat7-/- |
| SA408255 | E11.5_KO_5_PS_PI | brain cortex | E11.5 | Mboat7-/- |
| SA408256 | E11.5_KO_5_PC_PE | brain cortex | E11.5 | Mboat7-/- |
| SA408257 | E12.5_Het_3_PS_PI | brain cortex | E12.5 | Mboat7+/- |
| SA408258 | E12.5_Het_2_PS_PI | brain cortex | E12.5 | Mboat7+/- |
| SA408259 | E12.5_Het_1_PS_PI | brain cortex | E12.5 | Mboat7+/- |
| SA408260 | E12.5_Het_4_PS_PI | brain cortex | E12.5 | Mboat7+/- |
| SA408261 | E12.5_Het_4_PC_PE | brain cortex | E12.5 | Mboat7+/- |
| SA408262 | E12.5_Het_3_PC_PE | brain cortex | E12.5 | Mboat7+/- |
| SA408263 | E12.5_Het_2_PC_PE | brain cortex | E12.5 | Mboat7+/- |
| SA408264 | E12.5_Het_1_PC_PE | brain cortex | E12.5 | Mboat7+/- |
| SA408265 | E12.5_KO_2_PC_PE | brain cortex | E12.5 | Mboat7-/- |
| SA408266 | E12.5_KO_3_PS_PI | brain cortex | E12.5 | Mboat7-/- |
| SA408267 | E12.5_KO_3_PC_PE | brain cortex | E12.5 | Mboat7-/- |
| SA408268 | E12.5_KO_5_PS_PI | brain cortex | E12.5 | Mboat7-/- |
| SA408269 | E12.5_KO_4_PS_PI | brain cortex | E12.5 | Mboat7-/- |
| SA408270 | E12.5_KO_5_PC_PE | brain cortex | E12.5 | Mboat7-/- |
| SA408271 | E12.5_KO_2_PS_PI | brain cortex | E12.5 | Mboat7-/- |
| SA408272 | E12.5_KO_1_PS_PI | brain cortex | E12.5 | Mboat7-/- |
| SA408273 | E12.5_KO_1_PC_PE | brain cortex | E12.5 | Mboat7-/- |
| SA408274 | E12.5_KO_4_PC_PE | brain cortex | E12.5 | Mboat7-/- |
| SA408275 | E13.5_Het_5_PS_PI | brain cortex | E13.5 | Mboat7+/- |
| SA408276 | E13.5_Het_4_PS_PI | brain cortex | E13.5 | Mboat7+/- |
| SA408277 | E13.5_Het_3_PS_PI | brain cortex | E13.5 | Mboat7+/- |
| SA408278 | E13.5_Het_2_PS_PI | brain cortex | E13.5 | Mboat7+/- |
| SA408279 | E13.5_Het_1_PS_PI | brain cortex | E13.5 | Mboat7+/- |
| SA408280 | E13.5_Het_3_PC_PE | brain cortex | E13.5 | Mboat7+/- |
| SA408281 | E13.5_Het_5_PC_PE | brain cortex | E13.5 | Mboat7+/- |
| SA408282 | E13.5_Het_4_PC_PE | brain cortex | E13.5 | Mboat7+/- |
| SA408283 | E13.5_Het_2_PC_PE | brain cortex | E13.5 | Mboat7+/- |
| SA408284 | E13.5_Het_1_PC_PE | brain cortex | E13.5 | Mboat7+/- |
| SA408285 | E13.5_KO_2_PC_PE | brain cortex | E13.5 | Mboat7-/- |
| SA408286 | E13.5_KO_1_PC_PE | brain cortex | E13.5 | Mboat7-/- |
| SA408287 | E13.5_KO_1_PS_PI | brain cortex | E13.5 | Mboat7-/- |
| SA408288 | E13.5_KO_2_PS_PI | brain cortex | E13.5 | Mboat7-/- |
| SA408289 | E13.5_KO_3_PS_PI | brain cortex | E13.5 | Mboat7-/- |
| SA408290 | E13.5_KO_3_PC_PE | brain cortex | E13.5 | Mboat7-/- |
| Showing results 1 to 52 of 52 |
Collection:
| Collection ID: | CO003873 |
| Collection Summary: | Embryos at different gestational ages were collected from Mboat7 heterozygous intercrosses, and the cortices were subsequently dissected from the embryos. |
| Sample Type: | Brain cortex |
Treatment:
| Treatment ID: | TR003889 |
| Treatment Summary: | Not applicable. |
Sample Preparation:
| Sampleprep ID: | SP003886 |
| Sampleprep Summary: | Lipid extractions were conducted by the method of Bligh and Dyer. The extracted solutions were dried up with a centrifugal evaporator, dissolved in chloroform/methanol (2/1, v/v), and stored at -20 ºC. The phospholipid content of samples was quantified using a phosphorus assay. An aliquot of the extracted lipids was dried under a stream of nitrogen and dissolved in isopropanol:methanol (1:1, v/v) containing 0.25 µM internal standards (12:0/13:0 PC, PE, PS, PI) to achieve a final phospholipid concentration of 300 µM. |
Combined analysis:
| Analysis ID | AN006153 | AN006154 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | HILIC | HILIC |
| Chromatography system | Shimadzu Nexera X2 | Shimadzu Nexera X2 |
| Column | Merck SeQuant ZIC-HILIC (250 x 2.1mm, 1.8um) | Merck SeQuant ZIC-HILIC (250 x 2.1mm, 1.8um) |
| MS Type | ESI | ESI |
| MS instrument type | Triple quadrupole | Triple quadrupole |
| MS instrument name | ABI Sciex 4500 QTrap | ABI Sciex 4000 QTrap |
| Ion Mode | NEGATIVE | POSITIVE |
| Units | pmol/cortex | pmol/cortex |
Chromatography:
| Chromatography ID: | CH004674 |
| Instrument Name: | Shimadzu Nexera X2 |
| Column Name: | Merck SeQuant ZIC-HILIC (250 x 2.1mm, 1.8um) |
| Column Temperature: | 50 |
| Flow Gradient: | 0–22 min: 0% B to 40% B; 22–25 min: 40% B to 40% B; 25–30 min: 0% B |
| Flow Rate: | 0.3 mL/min |
| Solvent A: | 95% water/5% acetonitrile; 10 mM ammonium acetate |
| Solvent B: | 50% water/50% acetonitrile; 20 mM ammonium acetate |
| Chromatography Type: | HILIC |
MS:
| MS ID: | MS005858 |
| Analysis ID: | AN006153 |
| Instrument Name: | ABI Sciex 4500 QTrap |
| Instrument Type: | Triple quadrupole |
| MS Type: | ESI |
| MS Comments: | The instrument parameters for negative ion mode were as follows: curtain gas, 10 psi; collision gas, 7 arb. unit; ionspray voltage, −4500 V; temperature, 700°C; ion source gas 1, 30 psi; ion source gas 2, 70 psi. The specific detection of PS and PI species was performed using multiple reaction monitoring. 12:0/13:0 PI and PS were used as internal standards. Analyst (SCIEX) was used for data acquisition. MultiQuant (SCIEX) was used for data quantification. Gaussian smoothing width was 2.0 points. The peak area of the lipid species was divided by the corresponding internal standard area, and the total amount of phospholipids per cortex was calculated from the ratio of injection volume to total sample volume. The amounts of phospholipid per cortex are shown because the size of the E11-E13 cortices is not different between genotypes. |
| Ion Mode: | NEGATIVE |
| MS ID: | MS005859 |
| Analysis ID: | AN006154 |
| Instrument Name: | ABI Sciex 4000 QTrap |
| Instrument Type: | Triple quadrupole |
| MS Type: | ESI |
| MS Comments: | The instrument parameters for positive ion mode were as follows: curtain gas, 10 psi; collision gas, 7 arb. unit; ionspray voltage, 4500 V; temperature, 700°C; ion source gas 1, 30 psi; ion source gas 2, 50 psi. The specific detection of PC and PE species was performed using multiple reaction monitoring. 12:0/13:0 PC and PE were used as internal standards. Analyst (SCIEX) was used for data acquisition. MultiQuant (SCIEX) was used for data quantification. Gaussian smoothing width was 2.0 points. The peak area of the lipid species was divided by the corresponding internal standard area, and the total amount of phospholipids per cortex was calculated from the ratio of injection volume to total sample volume. The amounts of phospholipid per cortex are shown because the size of the E11-E13 cortices is not different between genotypes. |
| Ion Mode: | POSITIVE |
