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Blood Advances Aug 2023Erythrocytes undergo a well-defined switch from fetal to postnatal circulation, which is mainly reflected by the stage-specific expression of hemoglobin chains....
Erythrocytes undergo a well-defined switch from fetal to postnatal circulation, which is mainly reflected by the stage-specific expression of hemoglobin chains. Perinatal alterations in thrombopoiesis are poorly understood. We assessed the ontogenesis of platelet phenotype and function from early prematurity to adulthood. We recruited 64 subjects comprising 7 extremely preterm (27-31 weeks gestational age), 25 moderately preterm (32-36 weeks), 10 term neonates, 8 infants (<2 years), 5 children (2-13 years), and 9 adults (>13 years). Blood was withdrawn at up to 3 different time points in neonates (t1: 0-2, t2: 3-7, and t3: 8-14 days after birth). We found that the expression levels of the major surface receptors for fibrinogen, collagen, vWF, fibronectin, and laminin were reduced but correlated with decreased platelet size, indicating a normal surface density. Although CD62P and CD63 surface exposure upon stimulation with TRAP-6, ADP, or U46619 was unaltered or only slightly reduced in neonates, GPIIb/IIIa inside-out and outside-in activation was blunted but showed a continuous increase until adulthood, correlating with the expression of the GPIIb/IIIa regulating tetraspanin CD151. Platelet subpopulation analysis using automated clustering revealed that neonates presented with a CD63+/PAC-1- pattern, followed by a continuous increase in CD63+/PAC-1+ platelets until adulthood. Our findings revealed that the number of platelet-monocyte and platelet-neutrophil aggregates, but not platelet-lymphocyte aggregates, is increased in neonates and that neonatal aggregate formation depends in part on CD62P activation. Our PLatelets In Neonatal Infants Study (PLINIUS) provides several lines of evidence that the platelet phenotype and function evolve continuously from neonates to adulthood.
Topics: Humans; Pregnancy; Female; Infant, Newborn; Blood Platelets; Platelet Activation; Platelet Glycoprotein GPIIb-IIIa Complex; Infant, Premature; 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
PubMed: 37042931
DOI: 10.1182/bloodadvances.2023009824 -
Platelets Dec 2023Noncoding RNAs (ncRNAs) are a group of RNA molecules that cannot encode proteins, and a better understanding of the complex interaction networks coordinated by ncRNAs... (Review)
Review
Noncoding RNAs (ncRNAs) are a group of RNA molecules that cannot encode proteins, and a better understanding of the complex interaction networks coordinated by ncRNAs will provide a theoretical basis for the development of therapeutics targeting the regulatory effects of ncRNAs. Platelets are produced upon the differentiation of hematopoietic stem cells into megakaryocytes, 10 per day, and are renewed every 8-9 days. The process of thrombopoiesis is affected by multiple factors, in which ncRNAs also exert a significant regulatory role. This article reviewed the regulatory roles of ncRNAs, mainly microRNAs (miRNAs), circRNAs (circular RNAs), and long non-coding RNAs (lncRNAs), in thrombopoiesis in recent years as well as their roles in primary immune thrombocytopenia (ITP).
Topics: Humans; Thrombopoiesis; Blood Platelets; Megakaryocytes; MicroRNAs; RNA, Untranslated
PubMed: 36550091
DOI: 10.1080/09537104.2022.2157382 -
Blood Advances Jul 2023GATA1 mutations that result in loss of the N-terminal 83 amino acids are a feature of myeloid leukemia in children with Down syndrome, rare familial cases of...
GATA1 mutations that result in loss of the N-terminal 83 amino acids are a feature of myeloid leukemia in children with Down syndrome, rare familial cases of dyserythropoietic anemia, and a subset of cases of Diamond-Blackfan anemia. The Gata1s mouse model, which expresses only the short GATA1 isoform that begins at methionine 84, has been shown to have a defect in hematopoiesis, especially impaired erythropoiesis with expanded megakaryopoiesis, during gestation. However, these mice reportedly did not show any postnatal phenotype. Here, we demonstrate that Gata1s mutant mice display macrocytic anemia and features of aberrant megakaryopoiesis throughout life, culminating in profound splenomegaly and bone marrow fibrosis. These data support the use of this animal model for studies of GATA1 deficiencies.
Topics: Animals; Mice; Cell Lineage; Down Syndrome; Erythropoiesis; Protein Isoforms; Thrombopoiesis
PubMed: 36350717
DOI: 10.1182/bloodadvances.2022008124