The Fetal Hematopoietic Niche: Components and Mechanisms for Hematopoietic Stem Cell Emergence and Expansion

Purpose of Review Hematopoiesis is the process of generating all blood and immune cells, which is fueled at the root by self-renewing multipotent hematopoietic stem cells (HSCs). Unlike other systems in the body, hematopoiesis occurs in several waves in different organs (yolk sac, AGM, placenta, embryonic head, fetal liver, and fetal spleen) across ontogeny until it settles down in the bone marrow and remains there throughout adult life. Within a given hematopoietic organ, the microenvironmental niche plays critical roles in regulating HSCs and hematopoiesis by elaborating cytokines and other factors. Interestingly, under pathologic conditions in adults, hematopoiesis can be re-initiated in organs that are hematopoietic during fetal stages, such as the spleen and liver. Here we will review recent progresses on the identification of cellular components and mechanisms in these hematopoietic niches. We will also compare and contrast the niches to identify outstanding questions that are still unsolved in hematopoietic niche biology. Recent Findings Over the past several years, cutting-edge technologies have been applied to uncover the nature and mechanisms of the adult and fetal hematopoietic niches across tissues and organs in vivo. A general theme of the hematopoietic niche where endothelial cells and perivascular mesenchymal stromal cells are the core components is emerging. Summary In contrast to the maintenance niche in the adult bone marrow, the fetal hematopoietic niches promote HSC emergence and expansion. Elucidating the fetal hematopoietic niche mechanisms will help devise ways to amplify HSCs for clinical use. The on-and-off nature of the fetal hematopoietic niche suggests that the hematopoietic niche is highly dynamic. Understanding these dynamic changes offers the opportunity to harness the niche to promote hematopoiesis.