Human definitive haemogenic endothelium and arterial vascular endothelium represent distinct lineages

Autor: Amanda D. Yzaguirre, Andrea Ditadi, Gordon Keller, Xin Cheng, Christopher M. Sturgeon, Elizabeth Ng, Edouard G. Stanley, Geneve Awong, Lisa Azzola, Paul Gadue, Marion Kennedy, Deborah L. French, Joanna Tober, Nancy A. Speck, Andrew G. Elefanty
Rok vydání: 2015
Předmět:
Time Factors
Antigens
CD34
haemogenic endothelium
Cell Separation
Embryoid body
arterial
pluripotent
chemistry.chemical_compound
Induced pluripotent stem cell
5'-Nucleotidase
Endothelial Progenitor Cells
Hemogenic endothelium
Microscopy
Video
Receptors
Notch
Cell Differentiation
Arteries
Cell biology
Haematopoiesis
Phenotype
medicine.anatomical_structure
RUNX1
Core Binding Factor Alpha 2 Subunit
Notch signalling
Stem cell
vascular endothelium
CD184
Signal Transduction
Pluripotent Stem Cells
Receptors
CXCR5
Endothelium
DLL4
Biology
GPI-Linked Proteins
Article
Cell Line
Veins
definitive haematopoiesis
medicine
Humans
Cell Lineage
RUNX1C
venous
Precursor Cells
T-Lymphoid
Multipotent Stem Cells
Cell Biology
Hematopoietic Stem Cells
embryonic stem cell
Coculture Techniques
chemistry
Multipotent Stem Cell
CD73
multipotent progenitor
Biomarkers
Zdroj: Nature cell biology
ISSN: 1476-4679
1465-7392
DOI: 10.1038/ncb3161
Popis: The generation of haematopoietic stem cells (HSCs) from human pluripotent stem cells (hPSCs) will depend on the accurate recapitulation of embryonic haematopoiesis. In the early embryo, HSCs develop from the haemogenic endothelium (HE) and are specified in a Notch-dependent manner through a process named endothelial-to-haematopoietic transition (EHT). As HE is associated with arteries, it is assumed that it represents a subpopulation of arterial vascular endothelium (VE). Here we demonstrate at a clonal level that hPSC-derived HE and VE represent separate lineages. HE is restricted to the CD34(+)CD73(-)CD184(-) fraction of day 8 embryoid bodies and it undergoes a NOTCH-dependent EHT to generate RUNX1C(+) cells with multilineage potential. Arterial and venous VE progenitors, in contrast, segregate to the CD34(+)CD73(med)CD184(+) and CD34(+)CD73(hi)CD184(-) fractions, respectively. Together, these findings identify HE as distinct from VE and provide a platform for defining the signalling pathways that regulate their specification to functional HSCs.
Databáze: OpenAIRE
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