NOSTRIN: A novel modulator of trophoblast giant cell differentiation - ScienceDirect

Stem Cell Research

Shreeta Chakraborty^1¹ 

[1] Division of Cell Biology and Physiology, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, West Bengal, India^1

关键词: NOSTRIN;    Trophoblast stem cell;    Differentiation;    Giant cell;    Invasion;    Actin polymerization;    ICM;    Inner cell mass;    TE;    Trophoectoderm;    TSC;    Trophoblast stem cell (TSC);    NOSTRIN;    Nitric Oxide Synthase Trafficking INducer;    eNOS;    endothelial nitric oxide synthase;    NO;    nitric oxide;    PE;    pre-eclampsia;    PIH;    pregnancy-induced hypertension;    JZ;    Junctional zone;    LZ;    Labyrinth zone;    TGC;    trophoblast giant cell;    MEF;    mouse embryonic fibroblasts;   

DOI  :  10.1016/j.scr.2018.07.023

学科分类：生物科学（综合）

来源: Elsevier

【 摘 要 】

Differentiation-dependent expression of NOSTRIN in murine trophoblast cells prompted investigation on NOSTRIN's function in trophoblast differentiation. We show here that NOSTRIN levels increased in both mouse and rat placenta during gestation. NOSTRIN expression was not co-related to expression of eNOS precluding its eNOS mediated function. NOSTRIN transcripts were identified in trophoblast cells of the placenta, predominantly in trophoblast giant cells (TGC). Precocious over-expression of NOSTRIN during differentiation of trophoblast stem cells led to up-regulation of genetic markers associated with invasion (Prl4a1, Prl2a1) and TGC formation (Prl2c2, Prl3d1, Prl3b1). The functional consequence of NOSTRIN over-expression was increased TGC formation and trophoblast cell invasion. Furthermore, number of polyploid TGCs that arise by endoreduplication, were higher in presence of NOSTRIN. Early induction of NOSTRIN was associated with substantial decrease in G/F actin ratio and augmentation of N-WASP-Dynamin-NOSTRIN ternary complex formation that might be partially responsible for nucleation of actin filaments. NOSTRIN also formed a complex with Cdk1 and increased phosphorylation of T14 and Y15 residues that inhibits cytokinesis. Interestingly, SH3 domain deleted NOSTRIN was ineffective in eliciting NOSTRIN's function in differentiating trophoblast cells. These findings demonstrate that NOSTRIN potentiates trophoblast differentiation towards TGC trajectory that is critical for hemochorial placentation.

【 授权许可】

Unknown