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Global proteomic analyses of human cytotrophoblast differentiation/invasion.

ABSTRACT: During human pregnancy, cytotrophoblasts (CTBs) from the placenta differentiate into specialized subpopulations that play crucial 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 crucial 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. Although advances continue in describing the molecular features regulating the differentiation of these cells, assessment of their global proteomic changes at mid-gestation remain undefined. Here, using sequential window acquisition of all theoretical fragment-ion spectra (SWATH), which is 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 3026 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 as a foundation for further understanding CTB differentiation dynamics.

SUBMITTER: Chen H

PROVIDER: S-EPMC8276980 | biostudies-literature |

REPOSITORIES: biostudies-literature

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MTA3 regulates differentiation of human cytotrophoblast stem cells.

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Global transcriptome analyses of human and murine terminal erythroid differentiation.

Project description:We recently developed fluorescence-activated cell sorting (FACS)-based methods to purify morphologically and functionally discrete populations of cells, each representing specific stages of terminal erythroid differentiation. We used these techniques to obtain pure populations of both human and murine erythroblasts at distinct developmental stages. RNA was prepared from these cells and subjected to RNA sequencing analyses, creating unbiased, stage-specific transcriptomes. Tight clustering of transcriptomes from differing stages, even between biologically different replicates, validated the utility of the FACS-based assays. Bioinformatic analyses revealed that there were marked differences between differentiation stages, with both shared and dissimilar gene expression profiles defining each stage within transcriptional space. There were vast temporal changes in gene expression across the differentiation stages, with each stage exhibiting unique transcriptomes. Clustering and network analyses revealed that varying stage-specific patterns of expression observed across differentiation were enriched for genes of differing function. Numerous differences were present between human and murine transcriptomes, with significant variation in the global patterns of gene expression. These data provide a significant resource for studies of normal and perturbed erythropoiesis, allowing a deeper understanding of mechanisms of erythroid development in various inherited and acquired erythroid disorders.

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Project description:We profiled purified human cytotrophoblasts derived from second trimester placenta across four culture time points (0-39 h).

2021-03-02 | MSV000086970 | MassIVE

Transcriptome analysis of PPAR? target genes reveals the involvement of lysyl oxidase in human placental cytotrophoblast invasion.

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| S-EPMC7355036 | biostudies-literature

Elevated microRNA-125b inhibits cytotrophoblast invasion and impairs endothelial cell function in preeclampsia.

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BMP4-directed trophoblast differentiation of human embryonic stem cells is mediated through a ?Np63+ cytotrophoblast stem cell state.

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| S-EPMC3775414 | biostudies-literature

Matrix metalloproteinase 15 plays a pivotal role in human first trimester cytotrophoblast invasion and is not altered by maternal obesity.

Project description:Adequate anchoring of the placenta in the uterus through invasion of first trimester cytotrophoblasts (CTB) is required for a successful pregnancy. This process is mediated by matrix metalloproteinases (MMPs) and regulated by the maternal environment. Obesity is known to alter the intrauterine milieu and has been related to impaired invasion. We hypothesized that placental MMP15, a novel membrane-type MMP, is involved in CTB invasion and regulated by maternal obesity in early pregnancy. Thus, in this study MMP15 was immunolocalized to invasive extravillous and interstitial CTB. MMP15 silencing in chorionic villous explants using two different siRNAs reduced trophoblast outgrowth length (-35%, P ≤ .001 and -26%, P < .05) and area (-43%, P ≤ .001 and -36%, P ≤ .01) without altering trophoblast proliferation or apoptosis. Short-term treatment of primary first trimester trophoblasts with IL-6 (10 ng/mL), interleukin 10 (IL-10) (50 ng/mL), and tumor necrosis factor α (TNF-α) (10 ng/mL) did not affect MMP15 protein levels. Likewise, MMP15 mRNA and protein levels were unaltered between human first trimester placentas from control pregnancies vs those complicated with maternal obesity. Overall, our results suggest that the role of MMP15 in placental development and function in early pregnancy is limited to CTB invasion without being affected by short- and long-term inflammation.

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| S-EPMC3235251 | biostudies-literature

Recent human history governs global ant invasion dynamics.

Project description:Human trade and travel are breaking-down biogeographic barriers, resulting in shifts in the geographical distribution of organisms, yet it remains largely unknown whether different alien species generally follow similar spatiotemporal colonization patterns and how such patterns are driven by trends in global trade. Here, we analyse the global distribution of 241 alien ant species and show that these species comprise four distinct groups that inherently differ in their worldwide distribution from that of native species. The global spread of these four distinct species groups has been greatly, but differentially, influenced by major events in recent human history, in particular historical waves of globalization (approximately 1850-1914, and 1960-present), world wars and global recessions. Species in these four groups also differ in six important morphological and life-history traits and their degree of invasiveness. Combining spatiotemporal distribution data with life-history trait information provides valuable insight into the processes driving biological invasions and facilitates identification of species most likely to become invasive in the future.

| S-EPMC5495171 | biostudies-literature

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