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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
The third wave of embryonic hematopoiesis is associated with the emergence of HSCs that first appear within the intraembryonic aorta–gonad–mesonephros (AGM) region at murine E10.5 and between human gestation days 27 and 40 (Golub and Cumano 2013; Tavian et al. 2010). HSC are self-replicating, multilineage-producing hematopoietic progenitor cells. Hematopoietic cells also appear in the major umbilical and vitelline vessels and placenta (Samokhvalov et al. 2007). The HSCs migrate to the fetal liver and are detectable by the long-term repopulating activity of erythroid, myeloid, and lymphoid populations by E12.0 in the mouse embryo (Ema et al. 2000; Kumaravelu et al. 2002). Definitive hematopoiesis (EMP and HSC derived) occurs primarily in the liver from E11 in the mouse and approximately 4 to 6 weeks of gestation in humans (Frame et al. 2013), followed by a mixed distribution between liver, spleen, thymus, and bone marrow, and predominantly in the bone marrow by postnatal day 4 in the mouse and during the latter half of gestation in humans (Bloom and Brandt 2008; Boyd and Bolon 2010). As EMP- and HSC-derived blood cells are morphologically similar, it is currently unclear when the transition to HSC-derived hematopoiesis occurs in the fetus (Frame et al. 2013).
Turning Blood into Liver
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Bryon E. Petersen, Neil D. Theise
To address the above issue, we have reported a possible mechanism for oval cell activation in the injured liver and a possible mechanism for recruitment of bone marrow derived stem cells to the liver as a second wave of stem cell aided regeneration.44 During embryogenesis, the liver develops from a diverticulum of the floor of the foregut,20,45,46 where the founder cells invade the mesenchyme of the septum transversum. Endodermal cells eventually give rise to hepatocytes and the bile duct epithelial cells, while the mesenchyme gives rise to cells that make up the sinusoidal lining. During fetal development the liver functions as the hematopoietic organ.47,48 The hematopoietic cells found in the developing liver are of extra-hepatic origin, being derived from stem cells of the yolk sac32,49 and the aorta-gonad-mesonephros (AGM).50 Recruitment of the extra-hepatic cells to the embryonic liver is required for proper development, but the signals required by which HSCs respond and the mechanism of their movement within the fetus is not totally understood. It has been suggested that this movement could be controlled through the stromal cell-derived factor-1 alpha (SDF1α)/CXC chemokine receptor (CXCR)4 homing interaction between the hematopoietic and stromal cells.51,52 The importance of SDF1 α and CXCR4 in hematopoiesis is supported by observations of embryonic lethality in knockout mice with targeted disruption of the genes for either SDF1α53 or its receptor CXCR4.54-56 The expression of CXCR4 on the majority of CD34 positive and negative cells, and a demonstrated role of SDF 1 α in inducing chemotaxis in these cells, strongly suggests that the most primitive hematopoietic population including stem cells are responsive to a SDF1α chemotactic gradient.57-59 As stated earlier, several reports have shown hepatic oval cells and HSCs share a similar immunohistochemical profile, being positive for Thy-1, CD34 and c-Kit.36-39 In addition, the findings of Lagasse et al (2000) demonstrated that it was indeed the Sca+/Thylo/kit+/lin- sub-population of the bone marrow cells that was capable of becoming hepatic tissue.35 It would seem logical that some type of signal would be needed to bring cells from an extra-hepatic source to aid in the regenerative process.
The early life education of the immune system: Moms, microbes and (missed) opportunities
Published in Gut Microbes, 2020
Yolk sac and aorta-gonad mesonephros (AGM) hematopoiesis: Immune cells that arise from the first wave of hematopoiesis in the yolk sac have unique structural and physiological functions and equip the embryo with a repertoire of innate effectors consisting primarily of macrophages, mast cells, and Natural Killer (NK) cells. Long-lived macrophages generated from yolk-sac progenitors persist in tissues such as the liver, lung, brain, and epidermis,73,74 while those from HSC-derived monocytes are found in the gut, lung, and heart.75 Mast cells also display a similar ontogeny to macrophages and may arise from both yolk-sac and HSC-derived precursors that imprint them with distinct patterns of tissue residency.76,77 Pre-thymic lymphoid progenitors with long-term T cell engraftment capacity are found in the AGM region and arise before the appearance of embryonic HSCs in humans.78–80 In murine embryos, a subset of innate-like B cells called B-1 cells arise from hematogenic endothelia in both the yolk sac and the AGM region prior to HSCs, and seed the fetal liver.81
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].