Blood, Vol. 94 No. 8 (October 15), 1999:
pp. 2686-2695
Unique Differentiation Programs of Human Fetal Liver Stem Cells
Shown Both In Vitro and In Vivo in NOD/SCID Mice
Franck E. Nicolini,
Tessa L. Holyoake,
Johanne D. Cashman,
Pat
P.Y. Chu,
Karen Lambie, and
Connie J. Eaves
From the Terry Fox Laboratory, British Columbia Cancer Agency, and
the Department of Medical Genetics, University of British Columbia,
Vancouver, British Columbia, Canada.
Comparative measurements of different types of hematopoietic
progenitors present in human fetal liver, cord blood, and adult marrow
showed a large (up to 250-fold), stage-specific, but
lineage-unrestricted, amplification of the colony-forming cell (CFC)
compartment in the fetal liver, with a higher ratio of all types of CFC
to long-term culture-initiating cells (LTC-IC) and a lower ratio of
total (mature) cells to CFC. Human fetal liver LTC-IC were also found
to produce more CFC in LTC than cord blood or adult marrow LTC-IC, and
more of the fetal liver LTC-IC-derived CFC were erythroid. Human fetal liver cells regenerated human multilineage hematopoiesis in NOD/SCID mice with the same kinetics as human cord blood and adult marrow cells,
but sustained a high level of terminal erythropoiesis not seen in adult
marrow-engrafted mice unless exogenous human erythropoietin (Epo) was
injected. This may be due to a demonstrated 10-fold lower activity of
murine versus human Epo on human cells, sufficient to distinguish
between a differential Epo sensitivity of fetal and adult erythroid
precursors. Examination of human LTC-IC, CFC, and erythroblasts
generated either in NOD/SCID mice and/or in LTC showed the types of
cells and hemoglobins produced also to reflect their ontological
origin, regardless of the environment in which the erythroid precursors
were generated. We suggest that ontogeny may affect the behavior of
cells at many stages of hematopoietic cell differentiation through key
changes in shared signaling pathways.
