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Engraftment of embryonic hematopoietic cells in conditioned newborn
recipients
MC Yoder and K Hiatt
Department of Pediatrics, Herman B Wells Center for Pediatric Research,
Indiana University School of Medicine, Indianapolis 46202, USA.
Yolk sac hematopoiesis is characterized by restricted hematopoietic cell
differentiation. Although multipotent hematopoietic progenitor cells have
been identified in the early yolk sac, long-term multilineage repopulating
(LTMR) hematopoietic stem cell (HSC) activity has not been demonstrable
before day 11 postcoitus (PC) using standard transplantation assays. In the
present study, day-10 PC yolk sac hematopoietic cells were infused into
myeloablated congenic newborn pups and donor cell engraftment and
multilineage reconstitution of peripheral blood cells for at least 11
months in primary recipients was observed. In contrast, transplantation of
day-10 PC yolk sac cells into congenic adult recipients did not result in
engraftment despite pretransplant conditioning of the recipients or use of
recipients that were genetically deficient in stem cells. Although fresh
yolk sac cells were incapable of reconstitution when injected into adult
recipient mice, yolk sac donor-derived cells residing in the bone marrow of
primary newborn transplant recipients were capable of efficient
reconstitution of conditioned secondary recipient adult mice. Primary
newborn and secondary adult recipient animals engrafted with yolk sac cells
were observed to have normal peripheral blood white blood cell counts.
Lymphocyte subsets in peripheral blood, thymus, and spleen were also
similar to control animals. The distribution and frequency of
lineage-restricted progenitors derived from bone marrow of secondary
transplant recipients were normal. These results indicate that day-10 PC
yolk sac HSCs are capable of engrafting and reconstituting the
hematopoietic system of conditioned newborn but not adult recipient
animals. Furthermore, the ability of the yolk sac HSCs to differentiate
into all hematopoietic lineages in these recipients strongly suggests that
the local cellular microenvironment plays a prominent role in regulating
yolk sac HSC differentiation.
Volume 89,
Issue 6,
pp. 2176-2183,
03/15/1997
Copyright © 1997 by The American Society of Hematology
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