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Hematopoietic System
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
Kristin Henson, Tanasa Osborne, Gregory S. Travlos
Yolk sac blood islands and intraembryonic sites of hematopoiesis such as the AGM are thought to be formed from the hemangioblast, a mesodermal vascular and hematopoietic progenitor cell found transiently in the posterior primitive streak at approximately 12 to 18 hours of mouse gestation (Huber et al. 2004; Lancrin et al. 2010; Park et al. 2005). Hemangioblasts migrate to the sites of extraembryonic and intraembryonic hematopoiesis to form the endothelial and hematopoietic cells of these sites and produce hematopoietic precursors through hemogenic endothelium (Lancrin et al. 2009, 2010; Oberlin et al. 2010; Zovein et al. 2008).
RNA N6-methyladenosine methylation and skin diseases
Published in Autoimmunity, 2023
Yaqin Yu, Shuang Lu, Hui Jin, Huan Zhu, Xingyu Wei, Tian Zhou, Ming Zhao
Recent research demonstrated that the m6A modification of RNAs is crucial for haematopoietic development. Haematopoietic stem/progenitor cells (HSPCs) are derived from haemogenic endothelium during embryogenesis via the endothelial-to-haematopoietic transition (EHT) [75]. The continuous activation of Notch signalling could repress the emergence of HSPCs by blocking EHT in METTL3-deficient embryos [75,76]. METTL3 inhibits the endothelial Notch signalling pathway via YTHDF2-mediated mRNA decay [76]. Consistently, YTHDF2 was identified to repress inflammatory pathways in HSCs, which act as a protective factor in long-term HSC maintenance [77]. Gao et al. also found that conditional deletion of METTL3 in murine foetal liver activates the aberrant innate immune response, leading to haematopoietic failure and perinatal lethality [78]. These findings suggest that m6A maintains the balance of gene expression in endothelial and haematopoietic cells during EHT. In addition, shRNA-mediated depletion of METTL3 promotes cell differentiation and reduces cell proliferation in human haematopoietic stem/progenitor cells [79]. However, another study showed that deletion of YTHDF2 prevents the mRNA degradation of Wnt-target genes and survival-related genes, thus promoting the expansion and regenerative capacity of HSCs under stress conditions [80]. Taken together, the discoveries mentioned above suggest the complexity of m6A RNA methylation in the different developmental stages of haematopoiesis.
Incorporating placental tissue in cord blood banking for stem cell transplantation
Published in Expert Review of Hematology, 2018
Luciana Teofili, Antonietta R. Silini, Maria Bianchi, Caterina Giovanna Valentini, Ornella Parolini
Blood cell development is tightly connected to vessel formation and occurs in spatially and temporarily restricted waves. The onset of blood emergence (primitive hematopoiesis, starting around E7.25 in the mouse embryo) takes place in the yolk sac, where extra-embryonic mesoderm precursors differentiate to form endothelial cells and primitive erythrocytes, macrophage, and megakaryocyte progenitors. In the subsequent wave of blood specification (from E8.25 onwards), a specialized endothelial population, the hemogenic endothelium, produces definitive erythrocytes, most myeloid lineages, and B and T lymphoid progenitors. The hemogenic endothelium has been localized in the yolk sac, in the intra-embryonic aorta–gonad–mesonephros region, and in the placenta. Although still controversial, it is thought that hematopoietic stem cells (HSCs) generated within these sites migrate to the sites of definitive hematopoiesis, i.e. fetal liver and fetal bone marrow [4].
Hyalocyte origin, structure, and imaging
Published in Expert Review of Ophthalmology, 2022
Peter Wieghofer, Michael Engelbert, Toco YP Chui, Richard B Rosen, Taiji Sakamoto, J Sebag
Hematopoiesis can be subdivided into primitive hematopoiesis that is restricted to early embryonic development, and definitive hematopoiesis that takes place at later stages of development in the aorto-gonad-mesonephros (AGM) and the fetal liver (FL) as well as in the bone marrow established at the perinatal stages that remains active throughout life [52,53]. Primitive hematopoiesis is established in the hemogenic endothelium/hemangioblast of the extra-embryonic yolk sac that provides the blood island where precursors of both nucleated embryonic erythrocytes and primitive macrophages are created via the erythro-myeloid precursors (EMP) [54]. During development, EMPs further differentiate and their descendants colonize organs such as the brain or eye, before the intrinsic blood-brain or blood-retina barriers are formed, to become local tissue-resident macrophages including microglia [7,8,10,11,53,54]. Besides the developing organs that are reached via the embryonic circulation [3], they transiently colonize the fetal liver where progenitors of definitive hematopoiesis, derived from the AGM, can be found and establish the bone marrow later, prior to birth [53,55,56]. With regard to ciliary body macrophages, primitive hematopoiesis has been identified as the main source with only limited contribution from other hematopoietic organs including the fetal liver and the bone marrow [10]. With respect to hyalocytes, no embryonic fate mapping has been performed to date. However, human embryonic developmental stages have been investigated with respect to the local leukocyte populations by immunophenotyping [57]. The results suggest the presence of several markers that were attributed to hemangioblasts and suggested the existence of local blood islands remote from their well described localization in the yolk sac. Future experiments involving more contemporary methods including transcriptional profiling would help to decipher the former microscopic observations.