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.

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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.

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Study IDST003747
Study TitlePhosphatidylinositol remodeling by lysophospholipid acyltransferase 11 ensures embryonic radial glial cell integrity - part 1
Study SummarySince 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 NameKono
First NameNozomu
AddressHongo 7-3-1, Bunkyo-ku, Tokyo 113-033 JAPAN
Emailnozomu@mol.f.u-tokyo.ac.jp
Phone81-3-5841-4723
Submit Date2025-01-25
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2025-03-14
Release Version1
Nozomu Kono Nozomu Kono
https://dx.doi.org/10.21228/M82K0C
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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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 Gestational ages Genotype
SA408239E11.5_Het_1_PS_PIE11.5 Mboat7+/-
SA408240E11.5_Het_2_PC_PEE11.5 Mboat7+/-
SA408241E11.5_Het_4_PS_PIE11.5 Mboat7+/-
SA408242E11.5_Het_3_PS_PIE11.5 Mboat7+/-
SA408243E11.5_Het_2_PS_PIE11.5 Mboat7+/-
SA408244E11.5_Het_1_PC_PEE11.5 Mboat7+/-
SA408245E11.5_Het_3_PC_PEE11.5 Mboat7+/-
SA408246E11.5_Het_4_PC_PEE11.5 Mboat7+/-
SA408247E11.5_KO_4_PC_PEE11.5 Mboat7-/-
SA408248E11.5_KO_3_PC_PEE11.5 Mboat7-/-
SA408249E11.5_KO_2_PC_PEE11.5 Mboat7-/-
SA408250E11.5_KO_1_PC_PEE11.5 Mboat7-/-
SA408251E11.5_KO_1_PS_PIE11.5 Mboat7-/-
SA408252E11.5_KO_2_PS_PIE11.5 Mboat7-/-
SA408253E11.5_KO_3_PS_PIE11.5 Mboat7-/-
SA408254E11.5_KO_4_PS_PIE11.5 Mboat7-/-
SA408255E11.5_KO_5_PS_PIE11.5 Mboat7-/-
SA408256E11.5_KO_5_PC_PEE11.5 Mboat7-/-
SA408257E12.5_Het_3_PS_PIE12.5 Mboat7+/-
SA408258E12.5_Het_2_PS_PIE12.5 Mboat7+/-
SA408259E12.5_Het_1_PS_PIE12.5 Mboat7+/-
SA408260E12.5_Het_4_PS_PIE12.5 Mboat7+/-
SA408261E12.5_Het_4_PC_PEE12.5 Mboat7+/-
SA408262E12.5_Het_3_PC_PEE12.5 Mboat7+/-
SA408263E12.5_Het_2_PC_PEE12.5 Mboat7+/-
SA408264E12.5_Het_1_PC_PEE12.5 Mboat7+/-
SA408265E12.5_KO_2_PC_PEE12.5 Mboat7-/-
SA408266E12.5_KO_3_PS_PIE12.5 Mboat7-/-
SA408267E12.5_KO_3_PC_PEE12.5 Mboat7-/-
SA408268E12.5_KO_5_PS_PIE12.5 Mboat7-/-
SA408269E12.5_KO_4_PS_PIE12.5 Mboat7-/-
SA408270E12.5_KO_5_PC_PEE12.5 Mboat7-/-
SA408271E12.5_KO_2_PS_PIE12.5 Mboat7-/-
SA408272E12.5_KO_1_PS_PIE12.5 Mboat7-/-
SA408273E12.5_KO_1_PC_PEE12.5 Mboat7-/-
SA408274E12.5_KO_4_PC_PEE12.5 Mboat7-/-
SA408275E13.5_Het_5_PS_PIE13.5 Mboat7+/-
SA408276E13.5_Het_4_PS_PIE13.5 Mboat7+/-
SA408277E13.5_Het_3_PS_PIE13.5 Mboat7+/-
SA408278E13.5_Het_2_PS_PIE13.5 Mboat7+/-
SA408279E13.5_Het_1_PS_PIE13.5 Mboat7+/-
SA408280E13.5_Het_3_PC_PEE13.5 Mboat7+/-
SA408281E13.5_Het_5_PC_PEE13.5 Mboat7+/-
SA408282E13.5_Het_4_PC_PEE13.5 Mboat7+/-
SA408283E13.5_Het_2_PC_PEE13.5 Mboat7+/-
SA408284E13.5_Het_1_PC_PEE13.5 Mboat7+/-
SA408285E13.5_KO_2_PC_PEE13.5 Mboat7-/-
SA408286E13.5_KO_1_PC_PEE13.5 Mboat7-/-
SA408287E13.5_KO_1_PS_PIE13.5 Mboat7-/-
SA408288E13.5_KO_2_PS_PIE13.5 Mboat7-/-
SA408289E13.5_KO_3_PS_PIE13.5 Mboat7-/-
SA408290E13.5_KO_3_PC_PEE13.5 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.

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

Analysis:

Analysis ID:AN006153
Analysis Type:MS
Chromatography ID:CH004674
Num Factors:6
Num Metabolites:30
Units:pmol/cortex
  
Analysis ID:AN006154
Analysis Type:MS
Chromatography ID:CH004674
Num Factors:6
Num Metabolites:28
Units:pmol/cortex
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