NIH Researchers Unveil 3D Map of Human Retinal Development

Researchers at the National Institutes of Health (NIH) have mapped the 3D organization of genetic material during crucial stages of human retinal formation.

Using sophisticated models of lab-grown retinas, the team utilized deep Hi-C sequencing—a tool for studying 3D genome organization—to create high-resolution maps of chromatin at five pivotal developmental points.

Published in Cell Reports, the findings establish a critical foundation for comprehending clinical traits in various eye diseases, offering insights into the dynamic regulation of gene expression through chromatin architecture.

Lead investigator Dr. Anand Swaroop, Chief of the Neurobiology, Neurodegeneration, and Repair Laboratory at the National Eye Institute (NEI), emphasized the study's significance, stating, "These results provide insights into the heritable genetic landscape of the developing human retina, especially for the most abundant cell types that are commonly associated with vision impairment in retinal diseases."

The research focused on organoids, lab-grown tissue models engineered to replicate the function and biology of specific tissues. Through billions of sequenced and analyzed chromatin contact point pairs at each developmental stage, the study uncovered a dynamic spatial organization within the nucleus during retinal development. Notably, the findings shed light on the transformation of chromatin contact points and the hierarchy of compartments that influence gene expression.

Dr. Swaroop highlighted the potential impact of the datasets, noting, "The datasets resulting from this research serve as a foundation for future investigations into how non-coding sections of the genome are relevant for understanding divergent phenotypes in single gene mutation (Mendelian) disorders, as well as complex retinal diseases."

This research signifies a significant leap forward in understanding the intricate genetic mechanisms underlying retinal development and holds promise for advancing treatments for various eye conditions.

Reference

Zepeng Qu et al, Stage-specific dynamic reorganization of genome topology shapes transcriptional neighborhoods in developing human retinal organoids, Cell Reports (2023). DOI: 10.1016/j.celrep.2023.113543