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Ontogenesis of the hematon, a morphogenetic stromal unit that supports primary hematopoiesis in mouse bone marrow

Authors
Journal
Experimental Hematology
0301-472X
Publisher
Elsevier
Publication Date
Volume
28
Issue
7
Identifiers
DOI: 10.1016/s0301-472x(00)00447-1

Abstract

Abstract Development of primary hemato-lymphopoietic cells from a single stem cell (HSC) requires specific contacts with stromal cells. Here we studied the spatio-temporal emergence of these critical cell associations in the bone marrow (BM) in ontogeny and at homeostasis. In the adult mouse femur 5-10% of BM cells form a cohort of compact aggregates, the hematons in which a stromal cell web encloses CFU-Sd12, HPP-CFU, GM-CFU and BFU-E. During endochondral ossification of the femoral primordium CFU numbers increased proportionally with total nucleated cells from day 17 of gestation (E17). Unexpectedly, total BM taken from the femora between E17 and postnatal day 5 (d5) was unable to support autonomously the expansion of HPP-CFU and GM-CFU in long-term cultures. However, a gain-of-function switch in stromal cell competence occurred between d7–10. Autonomous cell-production ability was positively correlated with the emergence of compact hematon units in the BM at d7–10. In young adult mice the hematon fraction was 8-fold enriched in fibroblast CFU and 3.7-fold enriched in HSCs (LTC-IC) over the buffy coat. The hematon produced 50-fold more GM-CFU, 15-fold more HPP-CFU in LTBMC at day 28 and produced 8-fold more B lymphocytes (B220+) in myelopoietic/lymphopoietic “switch” cultures than did the buffy coat. We thus document that stromal hematopoietic units named hematons (i.) are specific morphogenetic structures, that emerge at a well-defined post-natal stage of development in long bones at the ultimate phase of endochondral ossification, (ii.) delineate discrete allocation territories for HSC seeding and development, (iii.) embody the most productive hematogenous compartment in the BM under homeostasis, and (i.v.) probably enclose a morphogenetic organizer of HSC development.

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