Authors: Li Wang, Yuting Liu, Mingming Chen, Lei Li, Ming Li, Ying Wang, Lin He, Jun Li
Journal: Cell
Publication Date: August 4, 2023
Background:
- Blood-forming stem cells (BFSCs), known as hematopoietic stem cells, produce all types of blood cells in the body.
- They arise from a specialized structure called the hemogenic endothelium (HE), formed during early human embryonic development.
- Understanding this process improves knowledge about blood disorders and could potentially lead to novel therapies.
Methods:
- The research team studied human embryos from 5 to 8 weeks of development, obtained with permission from donors after elective terminations.
- They used advanced microscopes, molecular imaging, and gene expression analysis to investigate the formation and development of the HE in precise three-dimensional (3D) detail.
Key Findings:
- Identification of Hemogenic Progenitors: In early human embryos, certain cells within the endothelial layer of blood vessels, termed "hemogenic progenitors," showed unique features.
- Migration toward Heart Region: These hemogenic progenitors underwent an intriguing migratory process called "intra-embryonic hematopoietic cell trafficking," moving from their starting points toward the region where the heart later forms.
- Hemoangioblasts Formation: At the cardiac crescent, the heart field mesoderm, a mesodermal tissue important for forming the heart and blood vessels, influenced the hemogenic progenitors, instructing them to adopt a new developmental fate as "hemoangioblasts."
- Hemoangioblasts to Hemogenic Endothelium: Hemoangioblasts further develop into clusters of HE cells in close association with vascular networks.
- Role of Vascular Plexus: They discovered that blood vessel networks form a dynamic "vascular plexus" around the HE clusters, playing crucial roles in facilitating the HE cells' survival and promoting a supportive environment for the emergence of BFSCs.
Significance:
- This study uncovers the early events that set the stage for BFSC development in human embryos. It provides a comprehensive road map of human hematopoietic development through meticulous 3D analysis.
- This detailed knowledge opens up new avenues for understanding embryonic developmental defects that disrupt blood formation and designing therapies to potentially regenerate functional blood systems in disease contexts.
