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Molecular evidence that in situ-transduced fetal liver hematopoietic
stem/progenitor cells give rise to medullary hematopoiesis in adult rats
DW Clapp, B Freie, WH Lee and YY Zhang
Department of Pediatrics, Indiana University School Of Medicine,
Indianapolis, USA.
We exploited the ability to transduce fetal liver hematopoietic
stem/progenitor cells in situ with recombinant retrovirus, together with
the ability to analyze proviral integration patterns into chromosomal DNA,
to detect the cellular and organ fate of hematopoietic stem and
progenitor-derived progeny in tissues and in the circulation of neonatal
and adult rats. Two hundred seventeen fetuses were injected with retrovirus
supernatant on day 16 of gestation, before the development of the bone
marrow cavity. The progeny of 41 stem and progenitor cells from 97 liveborn
rats were clonally identified. Pluripotent and lineage-restricted
stem/progenitor clones derived from the fetal liver consistently gave rise
to progeny in the marrow of newborn and adult rats. Patterns of
differentiation of transduced stem and progenitor cells fell into distinct
subsets. Blood cells derived from in situ transduced cells that originated
in the fetal liver circulated throughout the life span of the adult
animals. These data provide molecular evidence of the origin of medullary
cavity hematopoiesis by cells derived from the fetal liver that were
transduced in vivo, homed to the developing medullary cavity and
proliferated in a normal medullary hematopoietic microenvironment.
Volume 86,
Issue 6,
pp. 2113-2122,
09/15/1995
Copyright © 1995 by The American Society of Hematology
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