Biology subjects

Oh, E. S.

Publications and source records attributed to Oh, E. S..

2 recordsLinked to original sources

bioRxiv2026

The chronology of developing cells: are epigenomic and transcriptomic oscillations linked to their linear trajectories?

BackgroundDuring development, the specification of individual cell types requires orchestrated shifts in the activity of thousands of genes, each following precise and coordinated trajectories. The ability of this process to succeed with remarkable reliability, despite its immense complexity, suggests that at least some underlying principles of development are fundamentally simple. Building on recent findings from epigenetic aging research, we hypothesize that linear trajectories in developing cells are influenced by concurrent oscillatory dynamics, which may help ensure synchrony and robustness. ResultsSupporting this model, we demonstrate an association between oscillatory and linear dynamics in cytosine modifications in mouse intestinal organoids, as well as in the transcriptomes of C. elegans. Furthermore, we show that transcriptomes of single cells exhibited developmental chrono-heterogeneity, enabling reconstruction of oscillatory cycles which also correlate with linear changes. ConclusionsOscillation-mediated linear dynamics may represent an evolutionary invention for encoding molecular time and orchestrating developmental processes.

molecular biology↗

bioRxiv2023

A fluid biomarker reveals loss of TDP-43 splicing repression in pre-symptomatic ALS

Loss of TAR DNA-binding protein 43 kDa (TDP-43) splicing repression is well-documented in postmortem tissues of amyotrophic lateral sclerosis (ALS), yet whether this abnormality occurs during early-stage disease remains unresolved. Cryptic exon inclusion reflects functional loss of TDP-43, and thus detection of cryptic exon-encoded peptides in cerebrospinal fluid (CSF) could reveal the earliest stages of TDP-43 dysregulation in patients. Here, we use a newly characterized monoclonal antibody specific to a TDP-43-dependent cryptic epitope (encoded by the cryptic exon found in HDGFL2) to show that loss of TDP-43 splicing repression occurs in C9ORF72-associated ALS, including pre-symptomatic mutation carriers. In contrast to neurofilament light and heavy chain proteins, cryptic HDGFL2 accumulates in CSF at higher levels during early stages of disease. Our findings indicate that loss of TDP-43 splicing repression occurs early in disease progression, even pre-symptomatically, and that detection of HDGFL2s cryptic neoepitope may serve as a prognostic test for ALS which should facilitate patient recruitment and measurement of target engagement in clinical trials.

molecular biology↗