Developmental hematopoiesis: Ontogeny, genetic programming and conservation

Abstract

Hematopoietic stem cells (HSCs) sustain blood production throughout life and are of pivotal importance in regenerative medicine. Although HSC generation from pluripotent stem cells would resolve their shortage for clinical applications, this has not yet been achieved mainly because of the poor mechanistic understanding of their programming. Bone marrow HSCs are first created during embryogenesis in the dorsal aorta (DA) of the midgestation conceptus, from where they migrate to the fetal liver and, eventually, the bone marrow. It is currently accepted that HSCs emerge from specialized endothelium, the hemogenic endothelium, localized in the ventral wall of the DA through an evolutionarily conserved process called the endothelial-to-hematopoietic transition. However, the endothelial-to-hematopoietic transition represents one of the last steps in HSC creation, and an understanding of earlier events in the specification of their progenitors is required if we are to create them from naïve pluripotent cells. Because of their ready availability and external development, zebrafish and Xenopus embryos have enormously facilitated our understanding of the early developmental processes leading to the programming of HSCs from nascent lateral plate mesoderm to hemogenic endothelium in the DA. The amenity of the Xenopus model to lineage tracing experiments has also contributed to the establishment of the distinct origins of embryonic (yolk sac) and adult (HSC) hematopoiesis, whereas the transparency of the zebrafish has allowed in vivo imaging of developing blood cells, particularly during and after the emergence of HSCs in the DA. Here, we discuss the key contributions of these model organisms to our understanding of developmental hematopoiesis.

Temporal-Spatial Resolution Fate Mapping Reveals Distinct Origins for Embryonic and Adult Microglia in Zebrafish

“…To confirm that the IR-LEGO-CreER-loxP system could indeed provide a temporal-spatial restricted cell labeling with high efficiency and specificity in vivo, we focused on the RBI, VDA, and PBI, three well-known zebrafish hematopoietic tissues capable of giving rise to myeloid cells (Ciau-Uitz et al, 2014;Xu et al, 2012). The RBI, VDA, and PBI regions of double transgenic Tg(hsp70:mCherry-T2a-CreER T2 ;coro1a: loxP-DsRedx-loxP-GFP) embryos were heat-shocked (two to four shots for each region; each shot spot is 10 mm diameter in the focal plane and is irradiated for 2 min) by the 1,345 nm infrared laser at 12-16 hpf, 28-30 hpf, and 20-22 hpf, respectively.…”

Gata2b is a restricted early regulator of hemogenic endothelium in the zebrafish embryo

“…During embryogenesis, HSCs arise from a population of hemogenic endothelium, primarily within the ventral wall of the dorsal aorta (DA) (Ciau-Uitz et al, 2014;Clements and Traver, 2013;Dzierzak and Speck, 2008;Swiers et al, 2013;Taoudi and Medvinsky, 2007). Aortic endothelium transdifferentiates into HSCs via an endothelial-to-hematopoietic transition (EHT) (Chen et al, 2009;Jaffredo et al, 1998;Zovein et al, 2008), a process that is conserved across vertebrates (Bertrand et al, 2010;Boisset et al, 2014Boisset et al, , 2010Chen et al, 2009;Jaffredo et al, 2000Jaffredo et al, , 1998Kissa and Herbomel, 2010;Lam et al, 2010).…”

Analysis of Jak2 signaling reveals resistance of mouse embryonic hematopoietic stem cells to myeloproliferative disease mutation

“…[1][2][3] Relatively little is known about how this is mediated by the microenvironment and, more specifically, which soluble factors act on nascent HSCs to regulate their emergence, survival, expansion, and migration. 2 Understanding these complex processes and applying this knowledge to the recreation of the right conditions in vitro to facilitate the de novo generation and expansion of HSCs would be of immense clinical value.…”