Intrinsic gestational timing governs human cerebellar development after preterm birth
Year: 2026
Type: article
Study design: Observational Study
Abstract: Intrinsic programs shape brain maturation; however, which of these programs are perturbed by prematurity as well as the molecular pathways involved remain unknown. The human cerebellum serves as a paradigm of extrauterine development-its accelerated growth and circuit formation align with the third trimester, a period disrupted by preterm delivery. Using multimodal datasets encompassing in vivo neuroimaging and neurodevelopmental outcomes with postmortem spatial-transcriptomic and histopathological profiling, we show that prematurity diverts the cerebellar developmental trajectory. Cerebellar growth and functional outcomes scaled with gestational age, despite modifying perinatal exposures. Spatially resolved developmental programs underlying macroscopic trajectories were marked by incomplete granule cell maturation and impaired Purkinje cell structural refinement, which indicate lineage-specific developmental asynchrony. Thus, prematurity constitutes biologically displaced maturation, in which infants of equivalent postmenstrual age occupy divergent developmental states.
Source: Science
Authors: Georgios Sanidas, Gabriele Simonti, Javid Ghaemmaghami, Kyla Woyshner, Antonis Polyviou, Robinson Vidva, Courtney Lowe, Abhya Vij, Daniel Bittel, Maria Triantafyllou, Nora Wolff, Rodolfo Cardenas, Helen Chen, Francisco Almeida, Sniya Sudhakar, Kshitij Mankad, Ioannis Koutroulis, Henrik Sahlin Pettersen, Genevieve Stein-O’Brien, Dimitrios N Sidiropoulos, Vittorio Gallo, Panagiotis Kratimenos
Institutions: Children's National, George Washington University, Sheikh Zayed Institute for Pediatric Surgical Innovation, University of Michigan, Johns Hopkins University, Children's Hospital of Philadelphia, University of Pennsylvania, Norwegian University of Science and Technology, St Olav's University Hospital, Unidade Local de Saúde de Santo António EPE, Unidade Local de Saúde de Braga, University of Washington, Great Ormond Street Hospital, Seattle Children's Research Institute
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4413927581