Biology subjects

van Pelt, A. M. M.

Publications and source records attributed to van Pelt, A. M. M..

4 recordsLinked to original sources

bioRxiv2026

The metabolome and proteome of stem cell-derived human primordial germ cells: a multi-omics approach

Primordial germ cells (PGCs) are the population of cells that, in the human embryo, specify day 12 post-fertilization, and form the precursor cells for the future egg or sperm cells. Although in vitro differentiation of PGCs from human stem cells has been achieved, these primordial germ cell-like cells (hPGCLCs) fail to further mature. The reason for this is unclear. Previous studies in mice revealed that several specific metabolic changes occur during the maturation of these cells, which are essential for their developmental progress. However, very little is known about the metabolic profile of human primordial germ cells. In the severe scarcity of human PGCs, hPGCLCs serve as a research model to study PGC formation. To investigate this, we differentiated hPGCLCs using induced-pluripotent stem cells and performed a mass spectrometry analysis to establish their metabolome and proteome. These cells revealed distinct metabolic profile, with changes particularly at the proteome level. This included a shift between canonical and non-canonical citric acid cycle in hPGCLC, downregulation of late-stage glycolysis and reduction of nucleotide de novo synthesis. By providing an integrative map of these metabolic networks, we aim to provide insight on the influence of metabolism on human PGC development that could help improve methods for in vitro differentiation and maturation hPGCLCs.

developmental biology↗

bioRxiv2025

The pro-inflammatory cytokines IFN-α and TNF-α inhibit organoid-derived extravillous trophoblast invasion

Proper placental development requires differentiation and invasion of extravillous trophoblasts (EVTs) into the maternal decidua to ensure adequate remodeling of spiral arteries and support fetal growth. Perturbations in these processes are associated with pregnancy complications such as preeclampsia and fetal growth restriction. The incidence of these pregnancy complications is increased in women with immune-mediated inflammatory diseases, which are characterized by elevated levels of pro-inflammatory cytokines, such as interferon alpha (IFN-) and tumor necrosis factor alpha (TNF-). However, the direct effects of these cytokines on trophoblast differentiation and invasion remain unclear. Using human trophoblast organoid models, we demonstrate that IFN- and TNF- impair EVT invasion while preserving their differentiation capacity. High-resolution imaging of untreated organoid-decidua co-cultures revealed extensive invasion of organoid-derived trophoblasts into the decidual stroma and spiral arteries. In contrast, organoids treated with IFN-, in particular, exhibited markedly reduced invasion within this system. Transcriptome profiling indicated altered expression of several pathways involved in invasion upon cytokine treatment. These findings support the notion that elevated levels of IFN- and TNF- can directly impair trophoblast invasive capacity, potentially contributing to suboptimal placental development and adverse pregnancy outcomes in the context of inflammatory disorders.

developmental biology↗

bioRxiv2020

Tumors widely express hundreds of embryonic germline genes

We have recently described a class of 756 genes that are widely expressed in cancer, while normally restricted to adult germ cells, referred to as germ cell cancer genes (GC-genes). We hypothesized that carcinogenesis involves reactivation of biomolecular processes and regulatory mechanisms that, under normal circumstances, are restricted to germline development. This would imply that cancer cells share gene expression profiles with primordial germ cells (PGCs). We therefore compared the transcriptomes of human PGCs (hPGCs) and PGC-like cells (PGCLCs) with 17 382 samples from 54 healthy somatic tissues (GTEx) and 11 003 samples from 33 tumor types (TCGA), and identified 672 GC-genes, expanding the known GC-gene pool by 387 genes (51%). Because GC-genes specific to the embryonic germline are not expressed in any adult tissue, targeting these in cancer treatment may result in fewer side effects than targeting conventional cancer/testis (CT) or GC-genes and may preserve fertility. We anticipate that our extended GC-dataset enables improved understanding of tumor development and may provide multiple novel targets for cancer treatment development.

cancer biology↗

bioRxiv2017

Distinct prophase arrest mechanisms in human male meiosis

To prevent chromosomal aberrations to be transmitted to the offspring, strict meiotic checkpoints are in place to remove aberrant spermatocytes. However, in about 1% of all males these checkpoints cause complete meiotic arrest leading to azoospermia and subsequent infertility. We here unravel two clearly distinct meiotic arrest mechanisms that act during the prophase of human male meiosis. Type I arrested spermatocytes display severe asynapsis of the homologous chromosomes, disturbed XY-body formation and increased expression of the Y-chromosome encoded gene ZFY and seem to activate a DNA damage pathway leading to induction of p63 mediated spermatocyte elimination. Type II arrested spermatocytes display normal chromosome synapsis, normal XY-body morphology and meiotic crossover formation but have a lowered expression of several cell cycle regulating genes and fail to properly silence the X-chromosome encoded gene ZFX. Discovery and understanding of these meiotic arrest mechanisms increases our knowledge on how genomic stability is guarded during human germ cell development.

cell biology↗