Organotypic specification of stem-cell-nests during ontogenesis

I Blazsek, E Oberlin, B Peault

Research output: Contribution to journalArticlepeer-review

Abstract

Stem cells are the cornerstones of ontogenesis, compensatory
regeneration and safeguard lifelong tissue-specific functioning in
all self-renewing populations. However, a stem cell is not an autonomous
unit of development because a specialized microenvironment
or stromal niche controls and may re-specify the stem cell’s
destiny. In higher Metazoans, most organs are buit up by repetitive
subunits. We have shown that gaining full hematopoietic competence
requires the aggregation of stem cells (Thy-1, Sca-1, ckit
) in niche-forming stroma cells during mouse BM ontogenesis.
Similar aggregates can be isolated from liver anlagen that emerge
from the primitive gut at E8.5. Whole-mount vascular casting
(blue-alginate), immunolabeling and micro-cinematography showed
intrinsic emergence of vasculo-hemogenic cells from the dorsal
pericardial mesoderm around budding hepatic cords at E9.5. They
evolved a sinusoid framework via intussusceptive vasculogenesis
and produced primitive erythroid cells and scavenger macrophages.
Embryonic, colony-forming progenitors (EryP-CAFC,
adhM-CFU) appeared from E9.5, but definitive stem cells (LTCICd35)
colonized the primordium only from E12.0, when the
primordium became massively irrigated by peripheral blood.
Achieving stem-cell competence required aggregation with mesenchymal
cells (desmin, GFAP, EphB4) into compact, isolatable
niches. Niches were rich in HGF/SF, Shh, Bmp-4, SDF-1 and
evolved individually into organotypic units encountoured by a
cyclopamine sensitive mesodermal boundary. Thus, the dorsal
pericardial mesoderm (i.) supportes emergence of primitive angiohemogenic
cells, (ii.) evolves the Glisson’s capsule and interlobular
septa and (iii.) form niches required for organotypic development
of cholangio-hepatic and hemopoietic stem cells.
Original languageEnglish
Pages (from-to)76-76
Number of pages1
JournalExperimental Hematology
Volume31
Issue number7
DOIs
Publication statusPublished - Jul 2003

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