The osteo-hematon: Ontogenic development and biology of stem cell niches

I J Blazsek, E Oberlin, M Souyri, B Peault

Research output: Contribution to conferencePosterpeer-review

Abstract

The biological function of most vertebrate organs is carried out by many
tissue-specific functional units like the nephron, Lieberkühn crypt, islet of
Langerhans or hepato-biliary unit. Hemogenic stem cells (HSCs) irrigate
freely the whole body by the blood stream, but adult HSCs proliferate and
differentiate exclusively in the BM. We have postulated and documented
previously that the spongy BM was also organized into discrete, tissuespecific
structural-proliferative units, named hematon.
Here we show the spatial-temporal organization of stem cells and nestforming
cells, and basic mechanisms by which they sculpt together the
hematon in mouse and human liver and spongy BM. Video microscopy
uncovered the constitutive role of cardiomyogenic mesoderm and
subsequent association of mesodermal (desmin/GFAP+), hepatocholangiogenic
(CK19+, c-met+/CD49f+, connexin-43+) and
hematopoietic stem/progenitor cells into compact node-like niches, in early
liver organogenesis.
Single niches developed autonomously into complex hepatic units, and
at low seeding density they evolved into an interactive, contractil network.
The organization and integrity of self-bounded units was maintained by
distinct cell lineages emitting stimulatory and/or veto signaling factors
(FGF, HGF/SF, SHH, BMP4, SDF-1 and ephrinB2/EphB4). Targeted
inactivation of motif links disintegrated the network into isolated colonies,
resulting in either abortive or extensive growth.
Colonization and amplification of HSC in BM numerically correlated
with the node-like niches/hematons. Quantitative colony assays, FACS and
immunocytochemistry analyses allowed to identify mesenchymal stem
cells, preadipocytes/adipocytes, contractile myogenic cells, a vascular
meshwork, guardian macrophages and hemopoietic stem/progenitor cells
(Sca-1+/c-kit+/CD34+/Thy-1+) in the hematon. A hematon unit plays the
role of an organizing centre that emits growth, morphogen and communityeffect
mediating factors. The physical attachment of many hematons to
spongy bone suggests that they, together, may form the basic structuralfunctional
unit in the ultimate, fully competent BM. We suggest
designating these units and refer to as the osteo-hematon.
Original languageEnglish
Pages122-122
Number of pages1
DOIs
Publication statusPublished - Jul 2005

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