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Numerous human diseases stem from early developmental abnormalities. However, since most pediatric diseases and disorders are rare, children remain significantly underrepresented in research efforts. The Developmental Genotype-Tissue Expression (dGTEx) projects, published in Nature, aim to address critical gaps in understanding human and non-human primate (NHP) development. These initiatives expand the adult GTEx project by focusing on gene expression and regulation across developmental stages, spanning 74 tissue sites from 120 human donors and matching age groups from rhesus macaques and marmosets. By integrating whole-genome sequencing, single-cell, bulk, spatial transcriptomics, and chromatin accessibility data, the projects provide a comprehensive resource for investigating childhood disorders, genetic variations, and evolutionary conservation.

The dGTEx study highlights the unique genomic and cellular dynamics of early life, often underrepresented in research. While adult genomics has been widely studied, developmental stages—from prenatal to post-puberty—present distinct cellular phenotypes and gene regulation pathways that are critical to understanding pediatric diseases and their origins, including congenital malformations, childhood cancers, and metabolic disorders. By including diverse donor populations and emphasizing ethical, legal, and social considerations, the human dGTEx study strives to address disparities in genomic research and ensure broad representation.

For NHPs, the project leverages rhesus macaques and common marmosets to study developmental trajectories closely mirroring human biology. Marmosets, with unique reproductive traits like blood chimerism in dizygotic twins, and rhesus macaques, phylogenetically closer to humans, provide essential comparative insights into fetal and postnatal development.

Tissue collection involves rigorous coordination with Organ Procurement Organizations for human samples and primate research facilities for NHPs. Advanced techniques, such as single-nucleus RNA sequencing, chromatin accessibility assays, and spatial transcriptomics, allow precise mapping of developmental changes at cellular and tissue levels. These methods enhance understanding of the cellular diversity, regulatory mechanisms, and evolutionary differences in gene expression. The dGTEx initiative also confronts analytical challenges, including aligning cross-species data and addressing incomplete reference genomes for NHPs. Leveraging long-read sequencing and innovative computational tools, the project aims to normalize data and integrate findings with existing genomic resources like the Human Cell Atlas.

DAAD-Gastprofessorin at Julius-Maximilians-Universität Würzburg

By Mar Joanpere Foraster

DAAD-Gastprofessorin at Julius-Maximilians-Universität Würzburg