GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE266153 Query DataSets for GSE266153
Status Public on May 19, 2024
Title The GPI-anchor biosynthesis pathway is critical for syncytiotrophoblast differentiation and placental development
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The glycosylphosphatidylinositol (GPI) biosynthetic pathway in the endoplasmic reticulum (ER) is crucial for generating GPI-anchored proteins (GPI-APs), which are translocated to the cell surface and play a vital role in cell signaling and adhesion. This study focuses on two integral components of the GPI pathway, the PIGL and PIGF proteins, and their significance in trophoblast biology. We show that GPI pathway mutations impact on placental development impairing the development of the syncytiotrophoblast (SynT), and especially the SynT-II layer, which is essential for the establishment of the definitive nutrient exchange area within the placental labyrinth. CRISPR/Cas9 knockout of Pigl and Pigf in mouse trophoblast stem cells (mTSC) confirms the role of these GPI enzymes in syncytiotrophoblast differentiation. Mechanistically, impaired GPI-AP generation induces an excessive unfolded protein response (UPR) in the ER in mTSCs growing in stem cell conditions, akin to what is observed in human preeclampsia. Remarkably, the transcriptomic profile of Pigl- and Pigf-deficient cells separates human patient placental samples into preeclampsia and control groups suggesting an involvement of Pigl and Pigf in establishing a preeclamptic gene signature. Upon differentiation, the impairment of the GPI pathway hinders the induction of WNT signaling for early SynT-II development. Our study unveils the pivotal role of GPI biosynthesis in early placentation and uncovers a new preeclampsia gene expression profile associated with mutations in the GPI biosynthesis pathway, providing novel molecular insights into placental development with implications for enhanced patient stratification and timely interventions.
Overall design The RNA-seq experiment assesses the transcriptional changes in wild type (Vector) versus Pigl knockout (KO) or Pigf KO mouse trophoblast stem cells at three time points: under stem cell conditions at 0 days (0d), and after 3 days (3d) and 6 days (6d) of differentiation.
Contributor(s) Álvarez-Sánchez A, Grinat J, Doria-Borrell P, Mellado-López M, Pedrera-Alcocer É, Malenchini M, Messeguer S, Hemberger M, Pérez-García V
Citation(s) 38819479
Submission date Apr 29, 2024
Last update date Jun 06, 2024
Contact name Vicente Pérez García
Organization name Fundación Centro de Investigación Príncipe Felipe
Lab Mecanismos moleculares de invasión placentaria
Street address C/ Eduardo Primo Yúfera
City Valencia
ZIP/Postal code 46012
Country Spain
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (45)
GSM8241558 Pigf_KO_Day_0_clone 1_biol rep 1
GSM8241559 Pigf_KO_Day_0_clone 2_biol rep 2
GSM8241561 Pigf_KO_Day_0_clone 3_biol rep 3
BioProject PRJNA1106011

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE266153_raw_counts.xlsx 10.0 Mb (ftp)(http) XLSX
SRA Run SelectorHelp
Raw data are available in SRA

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap