Biology subjects

Park, L. S.

Publications and source records attributed to Park, L. S..

3 recordsLinked to original sources

bioRxiv2026

DNA methylation maintenance by DNMT1 is essential for human trophoblast stem cell homeostasis and differentiation

Proliferation of cytotrophoblasts (CTBs) and their differentiation into invasive extravillous trophoblasts (EVTs) are critical processes in early placental development. Defects in these processes are associated with adverse pregnancy outcomes, including recurrent pregnancy loss (RPL). There is evidence that reduced expression of the maintenance DNA methyltransferase DNMT1 in the placenta occurs in pregnancy loss and that RPL is associated with aberrant DNA methylation patterns. Therefore, we investigated the role of DNMT1 in human trophoblast growth and differentiation. Using human trophoblast stem cells (hTSCs), an in vitro analog to CTBs, we found that shRNA-mediated knockdown of DNMT1 led to decreased hTSC proliferation, genome-wide reductions in methylation, broad changes in gene expression, and impaired EVT differentiation. Transcriptome profiling of DNMT1-deficient hTSCs and hTSC-derived EVTs highlighted aberrant cytokine expression, drawing a connection to prior reports of immunological dysfunction in RPL. Finally, using a catalytic DNMT1 chemical inhibitor, we demonstrate the canonical methyltransferase activity of DNMT1 is essential for EVT differentiation and invasion. This study identifies new roles for DNMT1 in trophoblasts and addresses the molecular basis of the associations between DNMT1 expression, altered DNA methylation profiles, and RPL.

developmental biology↗

bioRxiv2025

TORC1-driven translation of Nucleoporin 44A promotes chromatin remodeling and germ cell-to-maternal transition in Drosophila

Oocyte specification is a critical developmental transition that requires the coordinated repression of germ cell-specific genes and activation of the maternal program to support embryogenesis. In Drosophila, the timely repression of germ cell and early oogenesis genes is essential for this transition, yet the mechanisms that coordinate this process remain unclear. Here, we uncover an unexpected translation-chromatin axis, where transient Target of Rapamycin Complex 1 (TORC1)-driven translation triggers chromatin remodeling, ensuring irreversible oocyte fate commitment. Through a screen, we identified ribosome biogenesis regulators, including Zinc finger protein RP-8 (Zfrp8) and TORC1 components, as key mediators of gene silencing. We show that TORC1 activity increases during oocyte specification, and disrupting ribosome biogenesis, translation, or TORC1 function prevents proper heterochromatin formation, leading to epigenetic instability. Polysome-seq analysis of zfrp8-depleted ovaries revealed that Zfrp8 is required for the translation of Nucleoporin 44A (Nup44A), a key nuclear pore complex (NPC) component. Given the role of the NPC in chromatin organization, independent disruption of Nup44A results in defective silencing of the germ cell and early oogenesis genes. Our findings reveal a mechanism in which translation-driven NPC remodeling coordinates heterochromatin establishment, facilitating the germ cell-to-maternal transition and ensuring proper oocyte fate commitment.

developmental biology↗

bioRxiv2018

Factor Structure and Heritability of Obsessive-Compulsive Traits in Children and Adolescents in the General Population

BackgroundObsessive-compulsive disorder (OCD) is a heritable childhood-onset psychiatric disorder that may represent the extreme of obsessive-compulsive (OC) traits that are widespread in the general population. We studied the factor structure and heritability of the Toronto Obsessive Compulsive Scale (TOCS), a new measure designed to assess traits associated with OCD in children and adolescents. We also examined the degree to which genetic effects are unique and shared between dimensions.\n\nMethodsOC traits were measured using the TOCS in 16,718 children and adolescents (6 to 18 years) at a local science museum. Factor analysis was conducted to identify OC trait dimensions. Univariate and multivariate twin modeling was performed to estimate the heritability of OC trait dimensions in a subset of twins (220 pairs).\n\nResultsSix OC dimensions were identified: Cleaning/Contamination, Hoarding, Rumination, Superstition, Counting/Checking, and Symmetry/Ordering. The TOCS total score (74%) and OC trait dimensions were heritable (30-77%). Hoarding was phenotypically distinct but shared genetic effects with other OC dimensions. Most of the genetic effects were shared between dimensions while unique environment accounted for the majority of dimension-specific variance, except for hoarding which had considerable unique genetic factors. A latent trait did not account for the shared variance between dimensions.\n\nConclusionsOC traits and individual OC dimensions were heritable, although the degree of shared and dimension-specific etiological factors varied by dimension. The TOCS is useful for genetic research of OC traits and OC dimensions should be examined individually and together along with total trait scores to characterize OC genetic architecture.

genetics↗