Abstract

During mouse ontogeny, hematopoietic cells arise from specialized endothelial cells, i.e., the hemogenic endothelium, and form clusters in the lumen of arterial vessels. Hemogenic endothelial cells have been observed in several embryonic tissues, such as the dorsal aorta, the placenta and the yolk sac. Recent work suggests that the mouse embryonic head also produces hematopoietic stem cells (HSCs)/progenitors. However, a histological basis for HSC generation in the head has not yet been determined because the hematopoietic clusters and hemogenic endothelium in the head region have not been well characterized. In this study, we used whole-mount immunostaining and 3D confocal reconstruction techniques to analyze both c-Kit+ hematopoietic clusters and Runx1+ hemogenic endothelium in the whole-head vasculature. The number of c-Kit+ hematopoietic cells was 20-fold less in the head arteries than in the dorsal aorta. In addition, apparent nascent hematopoietic cells, which are characterized by a “budding” structure and a Runx1+ hemogenic endothelium, were not observed in the head. These results suggest that head HSCs may not be or are rarely generated from the endothelium in the same manner as aortic HSCs.

Highlights

  • Hematopoietic stem cells (HSCs) and progenitors arise from several anatomically distinct regions during development [1,2,3]

  • Many studies have described the importance of the aortagonad-mesonephros (AGM) region and have revealed that clusters of hematopoietic cells are observed in the lumen of the dorsal aorta at the time of HSC generation [4,5,6,7,8]

  • Runx1-GFP, a marker of hemogenic endothelium, is not expressed in the head vasculature. These results suggest that embryonic head HSCs may not be or are rarely generated from the hemogenic endothelium in the same manner as aortic HSCs

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Summary

Introduction

Hematopoietic stem cells (HSCs) and progenitors arise from several anatomically distinct regions during development [1,2,3]. Many studies have described the importance of the aortagonad-mesonephros (AGM) region and have revealed that clusters of hematopoietic cells are observed in the lumen of the dorsal aorta at the time of HSC generation [4,5,6,7,8]. Hematopoietic Development in the Embryonic Head adult mice, suggesting that HSCs form within these hematopoietic clusters [9]. These cluster cells are generated by the transdifferentiation of hemogenic endothelial cells, a process known as endothelial-hematopoietic transition (EHT) [10,11,12,13]

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