Live imaging of Runx1 expression in the dorsal aorta tracks the emergence of blood progenitors from endothelial cells.
Blood cells of an adult vertebrate are continuously generated by hematopoietic stem cells (HSCs) that originate during embryonic life within the aorta-gonad-mesonephros region. There is now compelling in vivo evidence that HSCs are generated from aortic endothelial cells and that this process is critically regulated by the transcription factor Runx1. By time-lapse microscopy of Runx1-enhanced green fluorescent protein transgenic zebrafish embryos, we were able to capture a subset of cells within the ventral endothelium of the dorsal aorta, as they acquire hemogenic properties and directly emerge as presumptive HSCs. These nascent hematopoietic cells assume a rounded morphology, transiently occupy the subaortic space, and eventually enter the circulation via the caudal vein. Cell tracing showed that these cells subsequently populated the sites of definitive hematopoiesis (thymus and kidney), consistent with an HSC identity. HSC numbers depended on activity of the transcription factor Runx1, on blood flow, and on proper development of the dorsal aorta (features in common with mammals). This study captures the earliest events of the transition of endothelial cells to a hemogenic endothelium and demonstrates that embryonic hematopoietic progenitors directly differentiate from endothelial cells within a living organism.
Lam
Enid Yi Ni
EY
Department of Molecular Medicine & Pathology, School of Medical Sciences, University of Auckland, Auckland, New Zealand.
Hall
Christopher J
CJ
Crosier
Philip S
PS
Crosier
Kathryn E
KE
Flores
Maria Vega
MV
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000196:embryology / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000235:genetics; D006410:Hematopoiesis / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D007668:Kidney / Q000166:cytology / Q000196:embryology / Q000502:physiology; D008297:Male; D012039:Regional Blood Flow / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology / Q000502:physiology; D015533:Transcriptional Activation / Q000502:physiology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D050676:Core Binding Factor Alpha 2 Subunit; D029961:Zebrafish Proteins; C472526:runx1 protein, zebrafish; D049452:Green Fluorescent Proteins; D004815:Epidermal Growth Factor