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Blood, 15 February 2002, Vol. 99, No. 4, pp. 1183-1189
HEMATOPOIESIS
Stromal cell lines from mouse aorta-gonads-mesonephros
subregions are potent supporters of hematopoietic stem
cell activity
Robert A. J. Oostendorp,
Kirsty N. Harvey,
Nuray Kusadasi,
Marella F. T. R. de
Bruijn,
Chris Saris,
Rob E. Ploemacher,
Alexander L. Medvinsky, and
Elaine A. Dzierzak
From the Departments of Cell Biology and Genetics and
Hematology, Erasmus University, Rotterdam, The Netherlands; AMGEN,
Thousand Oaks, CA; and the Centre for Genome Research, University of
Edinburgh, United Kingdom.
The aorta-gonads-mesonephros (AGM) region autonomously generates
the first adult repopulating hematopoietic stem cells (HSCs) in the
mouse embryo. HSC activity is initially localized to the dorsal aorta
and mesenchyme (AM) and vitelline and umbilical arteries. Thereafter,
HSC activity is found in the urogenital ridges (UGs), yolk sac, and
liver. As increasing numbers of HSCs are generated, it is thought that
these sites provide supportive microenvironments in which HSCs are
harbored until the bone marrow microenvironment is established.
However, little is known about the supportive cells within these
midgestational sites, and particularly which microenvironment is most
supportive for HSC growth and maintenance. Thus, to better understand
the cells and molecules involved in hematopoietic support in the
midgestation embryo, more than 100 stromal cell lines and clones were
established from these sites. Numerous stromal clones were found to
maintain hematopoietic progenitors and HSCs to a similar degree as, or
better than, previously described murine stromal lines. Both the AM and
UG subregions of the AGM produced many supportive clones, with the most
highly HSC-supportive clone being derived from the UGs. Interestingly,
the liver at this stage yielded only few supportive stromal clones.
These results strongly suggest that during midgestation, not only the
AM but also the UG subregion provides a potent microenvironment for
growth and maintenance of the first HSCs.
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