Comparative circRNA Profiling in Human Erythroblasts Derived from Fetal Liver and Bone Marrow Hematopoietic Stem Cells Using Public RNA-Seq Data

Circular RNAs (circRNAs) are increasingly recognized as regulators of gene expression, although their roles in hematopoietic differentiation remain relatively understudied. This study compares circRNA expression profiles between erythroblasts derived from human fetal liver and bone marrow CD34⁺ hematopoietic stem cells using publicly available RNA-seq datasets (GEO: GSE90878). Twelve samples from each developmental source were analyzed. Differential expression analysis was performed, and circAtlas 3.0 was employed to predict interactions between circRNAs, microRNAs (miRNAs), and RNA-binding proteins. Differentially expressed miRNAs were curated from miRNA-seq data (GEO: GSE110936) profiling the same cell types. Principal component analysis of circRNA expression profiles demonstrated clear separation between erythroblasts from fetal liver and bone marrow, which was statistically confirmed by PERMANOVA (p = 0.001); though this effect size is small (R² = 0.065). One circRNA, circALS2(4).1, was significantly upregulated in bone marrow-derived erythroblasts (adjusted p < 0.05), and ten additional circRNAs showed suggestive evidence for differential expression (adjusted p < 0.1). The resulting interaction networks reveal distinct circRNA landscapes and suggest regulatory circuits that may contribute to developmental differences in human erythropoiesis, indicating that the functions of circRNAs in hematopoietic development remain to be further elucidated.