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Blood, 1 July 2001, Vol. 98, No. 1, pp. 6-12
FOCUS ON HEMATOLOGY
Generation of definitive hematopoietic stem cells from murine
early yolk sac and paraaortic splanchnopleures by
aorta-gonad-mesonephros region-derived stromal cells
Sahoko Matsuoka,
Kohichiro Tsuji,
Hiroaki Hisakawa,
Ming-jiang Xu,
Yasuhiro Ebihara,
Takefumi Ishii,
Daisuke Sugiyama,
Atsushi Manabe,
Ryuhei Tanaka,
Yasuo Ikeda,
Shigetaka Asano, and
Tatsutoshi Nakahata
From the Department of Clinical Oncology and Department
of Molecular Medicine, Institute of Medical Science, University of
Tokyo, Japan; Department of Internal Medicine, Keio University, Tokyo,
Japan; and Department of Pediatrics, Kyoto University, Japan.
There is controversy as to whether murine definitive hematopoiesis
originates from yolk sac (YS) or the intraembryonic region. This study reports the generation of definitive hematopoietic stem cells (HSCs) from both early YS and intraembryonic paraaortic splanchnopleures (P-Sp) on AGM-S3 stromal cells derived from the aorta-gonad-mesonephros (AGM) region at 10.5 days post coitum (dpc). YS
and P-Sp cells at 8.5 dpc generated no definitive hematopoiesis-derived colony-forming cells in cocultures with AGM-S3 cells, but spleen colony-forming cells and HSCs capable of reconstituting definitive hematopoiesis in adult mice simultaneously appeared on day 4 of coculture. Precursors for definitive HSCs were present in YS and P-Sp
at 8.0 dpc, a time when YS and embryo were not connected by blood
vessels. It is proposed that precursors with the potential to generate
definitive HSCs appear independently in YS and intraembryonic P-Sp and
that the P-Sp or AGM region affords the microenvironment that
facilitates generation of definitive hematopoiesis from precursors.
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