Erythroid/Myeloid Progenitors and Hematopoietic Stem Cells Originate from Distinct Populations of Endothelial Cells

• Published in: Cell stem cell 2011-12, Vol.9 (6), p.541-552
• Main Authors: Chen, Michael J., Li, Yan, De Obaldia, Maria Elena, Yang, Qi, Yzaguirre, Amanda D., Yamada-Inagawa, Tomoko, Vink, Chris S., Bhandoola, Avinash, Dzierzak, Elaine, Speck, Nancy A.
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Ly - genetics; Antigens, Ly - metabolism; Biological and medical sciences; Cell Differentiation - physiology; Cell differentiation, maturation, development, hematopoiesis; Cell Lineage; Cell physiology; Cells, Cultured; Core Binding Factor Alpha 2 Subunit - genetics; Core Binding Factor Alpha 2 Subunit - metabolism; Core Binding Factor beta Subunit - genetics; Core Binding Factor beta Subunit - metabolism; Embryo, Mammalian - cytology; Embryo, Mammalian - physiology; Endothelial Cells - cytology; Endothelial Cells - physiology; Erythroid Cells - cytology; Erythroid Cells - metabolism; Fundamental and applied biological sciences. Psychology; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - physiology; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Knockout; Molecular and cellular biology; Myeloid Cells - cytology; Myeloid Cells - physiology; Receptor Protein-Tyrosine Kinases - genetics; Receptor Protein-Tyrosine Kinases - metabolism; Receptor, TIE-2; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Transgenes
• ISSN: 1934-5909; 1875-9777
• DOI: 10.1016/j.stem.2011.10.003

Hematopoietic stem cells (HSCs) and an earlier wave of definitive erythroid/myeloid progenitors (EMPs) differentiate from hemogenic endothelial cells in the conceptus. EMPs can be generated in vitro from embryonic or induced pluripotent stem cells, but efforts to produce HSCs have largely failed. The formation of both EMPs and HSCs requires the transcription factor Runx1 and its non-DNA binding partner core binding factor β (CBFβ). Here we show that the requirements for CBFβ in EMP and HSC formation in the conceptus are temporally and spatially distinct. Panendothelial expression of CBFβ in Tek-expressing cells was sufficient for EMP formation, but was not adequate for HSC formation. Expression of CBFβ in Ly6a-expressing cells, on the other hand, was sufficient for HSC, but not EMP, formation. The data indicate that EMPs and HSCs differentiate from distinct populations of hemogenic endothelial cells, with Ly6a expression specifically marking the HSC-generating hemogenic endothelium. [Display omitted] ► CBFβ is required early for erythroid/myeloid progenitor formation, and later for HSCs ► Erythroid/myeloid progenitors and HSCs come from different endothelial cells ► Ly6a transgene expression marks HSC-producing hemogenic endothelium