Global proteomic analyses of human cytotrophoblast differentiation/invasion

Abstract

During human pregnancy, cytotrophoblasts (CTBs) from the placenta differentiate into specialized subpopulations that play critical roles in proper fetal growth and development. A subset of these CTBs differentiate along an invasive pathway, penetrating the decidua and anchoring the placenta to the uterus. A critical hurdle in pregnancy is the ability of these cells to migrate, invade, and remodel spiral arteries, ensuring adequate blood flow to nourish the developing fetus. While advances continue in describing the molecular features regulating the differentiation of these cells, assessment of their global proteomic changes at midgestation remain undefined. Here, using sequential window acquisition of all theoretical fragment-ion spectra (SWATH), a data-independent acquisition strategy, we characterized the protein repertoire of second trimester human CTBs during their differentiation towards an invasive phenotype. This mass spectrometry-based approach allowed identification of 3,026 proteins across four culture time points corresponding to sequential stages of differentiation, confirming the expression dynamics of established molecules and offering new information into other pathways involved. The availability of a SWATH CTB global spectral library serves as a beneficial resource for hypothesis generation and a foundation for further understanding of CTB differentiation dynamics.

scRNA-Seq of Cultured Human Amniotic Fluid from Fetuses with Spina Bifida Reveals the Origin and Heterogeneity of the Cellular Content

“…Based on the above and on the expression of the syncytiotrophoblast markers KISS1 [ 107 ] and SPINT1 [ 108 ] ( Figure 5 A), cells in cluster 11 were identified as SCT. These cells highly expressed cytokeratin genes, such as KRT8 , KRT18 , KRT17 and KRT19 ( Figure 5 B), which have also been described as trophoblast markers [ 109 , 110 , 111 ]. Using GO enrichment analysis of the gene sets representing each of the placental cell clusters, we observed that cells in cluster 11 demonstrated gene sets associated with epithelial cell phenotype and placenta development ( Figure 5 C).…”

Macrophage plasticity and function in cancer and pregnancy

“…Compared with studies on TAMs, studies on dMφ are limited to the mice models ( 152 , 153 ), which cannot represent authentic dMφ’s dynamic change along with the human pregnancy, and, due to ethical issues and technical difficulty, it is often infeasible to acquire abundant clinical samples. However, emerging and promising technologies including organoids, microfluidics, and organ-on-a-chip are paving the way for a deeper investigation of vasculogenesis involved in placental development and tumorigenesis ( 154 , 155 ). The effect of TAM and dMφ on vasculature remodeling is illustrated in Figure 4 .…”

A Proteomics-Based Identification of the Biological Networks Mediating the Impact of Epigallocatechin-3-Gallate on Trophoblast Cell Migration and Invasion, with Potential Implications for Maternal and Fetal Health

“…So far, the effect of EGCG on the protein expression in trophoblast cells remains unclear. A proteomics analysis is a useful approach for unraveling the mechanisms underlying the various activities of EGCG [ 18 ]. It has been used to analyze the EGCG-regulated proteins in many types of cells, demonstrating that EGCG can regulate and target different sets of proteins that are dependent on different cell types and different experimental conditions [ 19 , 20 , 21 ].…”