ArticleJournal of thrombosis and haemostasis : JTH2022
Age-restricted functional and developmental differences of neonatal platelets.
Article in Journal of thrombosis and haemostasis : JTH, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Inflammation, anemia, and vitamin D levels associate with infant thrombocytosis risk.Research and practice in thrombosis and haemostasis · 2026Article
- Cross-species comparison of platelet proteomes reveals developmentally regulated metabolic and inflammatory changes.Blood vessels, thrombosis & hemostasis · 2026Article
- Biliverdin reductase B as a new target in breast cancer.Breast cancer research : BCR · 2025Article
- Enhanced regenerative and developmental potential of embryonal and stem cell-derived platelets compared to adult platelets.Cell reports. Medicine · 2025Article
- Small molecule BLVRB redox inhibitor promotes megakaryocytopoiesis and stress thrombopoiesis in vivo.Nature communications · 2025Article
- CDK8/19 inhibition triggers a switch from mitosis to endomitosis in cord blood megakaryocytes.British journal of haematology · 2024Article
- Platelet proteomics emerges from the womb: mass spectrometry insights into neonatal platelet biology.Journal of thrombosis and haemostasis : JTH · 2024Article
- Quantitative label-free mass spectrometry reveals content and signaling differences between neonatal and adult platelets.Journal of thrombosis and haemostasis : JTH · 2024Article
- Heterogeneity of platelets and their responses.Research and practice in thrombosis and haemostasis · 2024Article
- Sources of variability in the human platelet transcriptome.Thrombosis research · 2023Review
- Ontogenesis of functional platelet subpopulations from preterm and term neonates to adulthood: The PLINIUS study.Blood advances · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundDevelopmental ontogeny of neonatal thrombopoiesis retains characteristics that are distinct from adults although molecular mechanisms remain unestablished.
methodsWe applied multiparameter quantitative platelet responses with integrated ribosome profiling/transcriptomic studies to better define gene/pathway perturbations regulating the neonatal-to-adult transition. A bioinformatics pipeline was developed to identify stable, neonatal-restricted platelet biomarkers for clinical application.
resultsCord blood (CB) platelets retained the capacity for linear agonist-receptor coupling linked to phosphatidylserine (PS) exposure and α-granule release, although a restricted block in cross-agonist activation pathways was evident. Functional immaturity of synergistic signaling pathways was due to younger ontogenetic age and singular underdevelopment of the protein secretory gene network, with reciprocal expansion of developmental pathways (E2F, G2M checkpoint, c-Myc) important for megakaryocytopoiesis. Genetic perturbations regulating vesicle transport and fusion (TOM1L1, VAMP3, SNAP23, and DNM1L) and PS exposure and procoagulant activity (CLCN3) were the most significant, providing a molecular explanation for globally attenuated responses. Integrated transcriptomic and ribosomal footprints identified highly abundant (ribosome-protected) DEFA3 (encoding human defensin neutrophil peptide 3) and HBG1 as stable biomarkers of neonatal thrombopoiesis. Studies comparing CB- or adult-derived megakaryocytopoiesis confirmed inducible and abundant DEFA3 antigenic expression in CB megakaryocytes, ~3.5-fold greater than in leukocytes (the most abundant source in humans). An initial feasibility cohort of at-risk pregnancies manifested by maternal/fetal hemorrhage (chimerism) were applied for detection and validation of platelet HBG1 and DEFA3 as neonatal thrombopoiesis markers, most consistent for HBG1, which displayed gestational age-dependent expression.
conclusionsThese studies establish an ontogenetically divergent stage of neonatal thrombopoiesis, and provide initial feasibility studies to track disordered fetal-to-adult megakaryocytopoiesis in vivo.
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