Successful engraftment of mouse fetal liver cells in early fetal recipients, after microinjection via the placental circulation, is attributable to seeding of the recipient's liver by a cell type that is ancestral to both the myeloid and lymphoid definitive lineages and is capable of sustained self-renewal and differentiation for more than 2 years. This primitive cell is therefore the normal totipotent hematopoietic stem cell (THSC). The use of a large series of mutant anemic recipients with decreasing severity of an endogenous stem-cell defect ( W W, Wv Wv, Wt Wt, Wv/+), and therefore of graded selective advantage to normal donor cells, has revealed that engraftment entails marginal numbers of cells-probably individual ones-in the least afflicted hosts. Thus the observed progressive and coordinate shift toward donor-strain erythrocytes, granulocytes and B and T lymphocytes, over time, indicates THSC expansion to form a larger stem-cell pool and normally regulated differentiation of cells from the pool. This transplant system allows allogeneic combinations with impunity and therefore provides many novel experimental possibilities for investigating THSC normal development, genetic abnormalities or neoplastic potential in relation to the intact developmental succession of hematopoietic tissue environments in vivo.
|Number of pages||9|
|State||Published - Sep 1982|
Bibliographical noteFunding Information:
This work was supported by grants from the US Public Health Service and by an appropriation from the Commonwealth of Pennsylvania. R. A. F. was the recipient of a fellowship from the W. W. Smith Trust. We thank Dr. Melvin J. Bosma and Ms. Carol L. Dewitt (both of the Institute for Cancer Research) for quantitative analyses of immunoglobulin allotypes.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology (all)