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Blood, 1 December 2000, Vol. 96, No. 12, pp. 3763-3771
HEMATOPOIESIS
Ontogenic emergence of the hematon, a morphogenetic stromal unit
that supports multipotential hematopoietic progenitors in mouse
bone marrow
Istvàn Blazsek,
Jalila Chagraoui, and
Bruno Péault
From INSERM Unité 506 and Institut du Cancer et
d'Immunogénétique, Hôpital Paul Brousse, Villejuif,
France.
Development of the full repertoire of
hematopoietic-lymphopoietic cells from a single stem cell
requires specific contacts with stromal cells. The spatio-temporal
organization of these cell associations in the bone marrow in ontogeny
is, however, not well understood. In the adult, 10% of marrow cells
form a cohort of compact aggregates, the hematon. In the hematon
mesenchymal cells (Stro-1+), perivascular lipocytes
(desmin+), endothelial cells (CD34+,
Flk-1+, Sca-1+), and macrophages amalgamate
with the hematopoietic progenitors long-term culture-initiating cells
(LTC-IC), cobblestone area-forming cell (CAFC),
high-proliferative-potential colony-forming
unit (HPP-CFU), granulocyte-macrophage (GM)-CFU,
and burst-forming unit-erythroid (BFU-E). During endochondral
ossification of the femur, GM-CFU and day 7 CAFC numbers increased
progressively from day 17 of gestation, but primitive, day 35 LTC-IC
appeared from postnatal day 2. Unexpectedly, bone marrow (BM) taken
between embryonic day 17 and day 5 was unable to support myeloid cell production in long-term cultures or to support day 35 LTC-IC growth. However, a gain in stromal cell competence occurred between days 7 and
10, which was correlated with the emergence of hematon in the BM. Thus,
acquisition of hematopoietic competence by BM lags behind for
approximately 10 days after the initial hematopoietic cell influx. In
the adult, the hematon fraction was 3.7-fold enriched in day 35 LTC-IC
over the buffy coat. It produced more GM-CFU and HPP-CFU in myeloid
culture and more B cells in lymphopoietic "switch" cultures. It is
reported that stromal hematopoietic units named hematons are specific
morphogenetic structures that emerge at a well-defined postnatal stage
of development in long bones, delineate discrete territories for
hematopoietic stem cell seeding and development, embody the most
productive hematogenous compartment in the BM, and probably
enclose a morphogenetic organizer.
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