Single-cell transcriptomic and spatial analysis technologies enable the study of cellular diversity and tissue organization within the complex anatomical structures of adult vertebrates at the molecular level. However, the large physical size of most vertebrate models poses technical limitations to mapping cellular states at the whole-body scale and with full resolution. This situation necessitates the creation of comprehensive molecular maps using miniaturized vertebrate models to holistically examine cell dynamics in homeostasis (internal balance) and tissue repair processes.
In their comprehensive study aimed at addressing this critical technical shortcoming in vertebrate biology, Atabay and colleagues sought to create a whole-body single-cell transcriptome and spatial atlas of the adult Danionella cerebrum model—a miniature teleost (bony fish) species characterized by optical transparency and high regenerative capacity. The researchers aimed to elucidate the regional distribution of cell types, adult spatial memory, pedomorphic (retention of larval traits in the adult stage) structures, and the fundamental molecular dynamics underlying nervous system regeneration processes, while preserving the organism’s small nervous system and complex anatomical features.
Accordingly, 607,370 cells obtained from 12 different anatomical regions—isolated via microdissection from adult D. cerebrum individuals—were screened using scRNA-seq (single-cell RNA sequencing) technology and analyzed in detail across 40 major tissue classes. To verify the anatomical locations of the obtained cellular profiles with high accuracy in a spatial plane, MERFISH (multiplexed error-corrected fluorescence in situ hybridization) and HCR-FISH (hybridization chain reaction fluorescence in situ hybridization) methods were applied using a custom panel of 500 genes. In addition, surgical injury models applied to the telencephalon (forebrain) region were sampled at intervals ranging from 12 hours to 30 days and monitored via EdU integration and time-dependent gene expression cascades.
The key findings indicate that the transcriptomic similarities among neural cells in the central nervous system are shaped more by their regional brain location than by their neurotransmitter (molecular signal transmitters between nerve cells) identity; that neurons belonging to different neurotransmitter classes exhibit transcriptomic similarity within the same region; and that glutamatergic neurons, in particular, exhibit a distinct dorsal bias. While it was determined that the regional expression of Hox genes along the anteroposterior (front-to-back) axis is preserved in connective tissue cells, it was also found that the evolutionarily conserved patterning programs for pectoral and pelvic appendages (tbx5a, tbx4, pitx1) remain active in adult fins Pedomorphic analyses revealed a mosaic coexistence of adult and larval features in the living organism; in telencephalic regeneration, however, a highly organized repair program was observed, comprising stages of acute immune response, myeloid cell recruitment, radial glia proliferation, and neurogenesis, and it was also found that a systemic compensatory response was triggered in the uninjured contralateral hemisphere.
This comprehensive study presents the first spatially resolved whole-body single-cell atlas of an adult vertebrate, serving as a valuable reference resource for neuroscience, stem cell biology, and evolutionary development research. The molecular data obtained from this research provide a reliable foundation for future studies aimed at understanding vertebrate brain regionalization, tissue homeostasis, and the regenerative capacity in non-mammalian vertebrate models.
Translated by: Yağmur Aktepe
Editor: Hazel Birgül
Reference: Atabay, K. D., Aoude, P., Park, C., Kadobianskyi, M., Paugois, O. H., Judkewitz, B., & Reddien, P. W. (2026). Whole-body single-cell atlas of an adult vertebrate, Danionella cerebrum. Science, 394(6823), Article eaeg1125. https://doi.org/10.1126/science.aeg1125
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