Haemopoietic stem cells during development of mouse embryo

Area of Science:

• Developmental Biology
• Hematology
• Stem Cell Biology

Background:

• Mammalian hematopoiesis initiates in the yolk sac around the 7th day of gestation.
• Erythropoietin (EPO)-responsive cells are present from day 7, but myeloid-committed cells (responding to GM-CSF) appear later, on day 10.
• Multipotent stem cells, detected as late colony-forming unit spleen (CFU-s) on day 12, also emerge during this period.

Purpose of the Study:

• To investigate the origin and characteristics of early hematopoietic stem cells in mouse embryos.
• To differentiate between yolk sac-derived and embryonic-derived hematopoietic stem cell populations.
• To determine the timing of pluripotent stem cell emergence for liver hematopoiesis.

Main Methods:

• Detection of erythropoietin (EPO)-responsive cells.
• Demonstration of granulocyte-macrophage colony-stimulating factor (GM-CSF)-responsive myeloid progenitor cells.
• Assessment of late colony-forming unit spleen (CFU-s) activity.
• Analysis of primitive pluripotent stem cells capable of bone-marrow repopulation.

Main Results:

• Yolk sac hematopoiesis is established by day 7, with EPO-responsive cells present.
• Myeloid progenitor cells and multipotent stem cells (CFU-s) are detectable from day 10 and day 12, respectively.
• Liver hematopoiesis, starting on day 13, is attributed to primitive pluripotent stem cells originating within the embryo, not the yolk sac.

Conclusions:

• Early embryonic stem cells (days 7-10) appear to be a primitive population restricted to the yolk sac.
• The primitive hematopoietic pluripotent stem cells responsible for liver hematopoiesis arise de novo within the embryo.
• The yolk sac does not harbor primitive pluripotent stem cells capable of repopulating lethally irradiated bone marrow.