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Multicohort analysis unveils axon guidance pathways linking small for gestational age to spirometric restriction.

ABSTRACT: Children born small for gestational age (SGA) face elevated risks of metabolic, cardiovascular, respiratory, and neurodevelopmental disorders, as well as premature mortality, yet the underlying mechanisms remain only partly understood. We analyze blood proteomic data from multiple birth cohorts to identify molecular pathways linked to SGA and to later-life lung function. We find that approximately one-third of SGA children exhibit a distinct molecular endotype marked by dysregulation of axon-guidance proteins in cord blood. In peripheral blood collected later in life, these proteins are inversely associated with contemporaneous spirometric restriction. These findings offer new insight into the developmental origins of chronic disease and highlight axon-guidance pathways as promising targets for investigating multiorgan morbidity. This repository accompanies the publication entitled “Multicohort analysis unveils axon guidance pathways linking small for gestational age to spirometric restriction.”

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood

SUBMITTER: James Read

LAB HEAD: Anthony Bosco

PROVIDER: PAD000036 | Pride | 2026-04-02

REPOSITORIES: Pride

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			Action	DRS
	CADRE_Cord_aptamer_info_comb.csv	Csv
	CADRE_Cord_data_comb.csv	Csv
	CADRE_Cord_pheno_comb.csv	Csv
	CADRE_LL_aptamer_info_comb.csv	Csv
	CADRE_LL_data_comb_rm.csv	Csv

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Project description:The abstract of the manuscript titled "Signalling pathways involved in adult heart formation revealed by gene expression profiling in Drosophila" is given below: "Drosophila provides a powerful system for defining the complex genetic programs that drive organogenesis. Under control of the steroid hormone ecdysone, the adult heart in Drosophila forms during metamorphosis by a remodelling of the larval cardiac organ. Here, we evaluated the extent to which transcriptional signatures revealed by genomic approaches can provide new insights into the molecular pathways that underlie heart organogenesis. Whole-genome expression profiling at 8 successive time-points covering adult heart formation revealed a highly dynamic temporal map of gene expression through 13 transcript clusters with distinct expression kinetics. A functional atlas of the transcriptome profile strikingly points to the genomic transcriptional response of the ecdysone cascade, and a sharp regulation of key components belonging to a few evolutionary conserved signalling pathways. A reverse genetic analysis provided evidence that these specific signalling pathways are involved in discrete steps of adult heart formation. In particular, the Wnt signalling pathway is shown to participate in inflow tract and cardiomyocyte differentiation, while activation of the PDGF-VEGF pathway is required for cardiac valve formation. Thus, a detailed temporal map of gene expression can reveal signalling pathways responsible for specific developmental programs and provides here substantial grasp into heart formation." Keywords: Time-course analysis Total RNAs were prepared from dissected cardiac tubes of Drosophila staged pupae at 8 successive time-points 21, 24, 27, 30, 33, 36, 42 and 48 hours after puparium formation covering adult heart organogenesis. For each time-point sample, 5 cardiac tubes were hand dissected from staged individuals. Four independent biological replicates were analyzed to confer a high reproducibility and statistical significance of the expression data. PolyA+ RNAs were linearly amplified (32 amplifications), labelled (32 with Cy3 and 32 with Cy5), and used for hybridization on Drosophila high-density oligonucleotide (INDAC) dual-channel microarrays (32 arrays) according to a loop-design dedicated to time-course experiments. Given the same number of arrays (8), a simple loop design is more efficient than a reference design: direct comparisons, smallest variance for log ratios, balancing varieties with dye-swapping (including technical replicates) and no reference sample needed (which has no intrinsic interest in our study). A graphical representation of the loop design used on this study is showed in the associated manuscript.

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Multicohort analysis unveils axon guidance pathways linking small for gestational age to spirometric restriction.

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