![]() ![]() Plots (left) indicate the gating strategies used to define HSCs (c-kit+Lineage-Sca1+ Flk2-CD150+ CD48- BM cells) and multipotent progenitors (MPPs KLS Flk2+CD150- CD48+ BM cells). Flow cytometric analysis of reporter activity in the P14 (I) and adult (J) BM. I and J, A fraction of neonatal HSCs express GFP, whereas all adult HSCs express Tom. Bottom row depicts reporter gene fluorescence profiles of cells within gated regions shown above. Top row depicts gating strategy for stem and progenitor cell compartments. Plots depict flow cytometric analysis of reporter activity within the hematopoietic stem cell- and progenitor-enriched compartments of the YS at E9.5 (C) the YS (D) and AGM (E) at E10.5 the FL (F) and PL (G) at E12.5 and the FL at E14.5 (H) in FlkSwitch embryos. C-H, Phenotypic stem and progenitor populations from E10.5-14.5 contain both Tom+ and GFP+ cells. The bone marrow (BM) becomes the main site of HSC residence at birth, where they persist throughout life. Late fetal hematopoiesis occurs primarily in the FL. ![]() Definitive hematopoiesis occurs in the aorta-gonad-mesonephros region (AGM), the placenta (PL), and the fetal liver (FL) in the mid-gestation embryo. Primitive hematopoiesis initiates in the blood islands (BI) of the early embryonic yolk sac (YS). B, Chronological depiction of developmental hematopoiesis. Flk2-driven Cre expression leads an irreversible switch from Tomato to GFP expression in Flk2-expressing cells and their progeny. All rights reserved.Ī, Strategy for generation of the FlkSwitch lineage tracing mouse model. Thus, these developmentally restricted HSCs (drHSCs) define the origin and generation of early lymphoid cells that play essential roles in establishing self-recognition and tolerance, with important implications for understanding autoimmune disease, allergy, and rejection of transplanted organs.ĭevelopment hematopoiesis hematopoietic stem cell immune cells innate-like B and T lymphocytes lineage potential lineage tracing self-renewal tissue resident transplantation.Ĭopyright © 2016 Elsevier Inc. These HSCs are fully multipotent, yet they display both higher lymphoid cell production and greater capacity to generate innate-like B and T lymphocytes as compared to coexisting fetal HSCs and adult HSCs. Using an irreversible lineage-tracing model, we identify a definitive hematopoietic stem cell (HSC) that supports long-term multilineage reconstitution upon transplantation into adult recipients but does not persist into adulthood in situ. However, the mechanisms underlying differential cell production to generate a layered immune system during hematopoietic development are unclear. The generation of distinct hematopoietic cell types, including tissue-resident immune cells, distinguishes fetal from adult hematopoiesis. ![]()
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