Hepatic hematopoiesis in the mouse embryo is preceded by two hematopoietic waves, one in the yolk sac, and the other in the paraaortic splanchnopleura, the presumptive aorta-gonad-mesonephros region that gives rise to prenatal and postnatal blood stem cells. An homologous intraembryonic site of stem cell emergence was previously identified at 5 weeks of human gestation, when hundreds of CD34(++)Lin- high-proliferative potential hematopoietic cells border the aortic endothelium in the preumbilical region. In the present study, we have combined immunohistochemistry, semithin section histology, fluorescence-activated cell sorting and blood cell culture in an integrated study of incipient hematopoiesis in the human yolk sac, truncal arteries and embryonic liver from 21 to 58 days of development. The chronology of blood precursor cell emergence in these distinct tissues suggests a pivotal role in the settlement of liver hematopoiesis of endothelium-associated stem cell clusters, which emerge not only in the dorsal aorta but also in the vitelline artery. Anatomic features and in vitro functionality indicate that stem cells develop intrinsically to embryonic artery walls from a presumptive territory whose blood-forming potential exists from at least 24 days of gestation.

Andrew
T. A.
,
Owen
J. J.
(
1978
)
Studies on the earliest sites of B cell differentiation in the mouse embryo.
Dev. Comp. Immunol
2
,
339
346
Auerbach
R.
,
Huang
H.
,
Lu
L. S.
(
1996
)
Hematopoietic stem cells in the mouse embryonic yolk sac.
Stem Cells
14
,
269
280
Bechtold
T. E.
,
Smith
P. B.
,
Turpen
J. B.
(
1992
)
Differential stem cell contributions to thymocyte succession during development of Xenopus laevis.
J. Immunol
148
,
2975
2982
Bloom
W.
,
Bartelmez
G. W.
(
1940
)
Hematopoiesis in young human embryos.
Am. J. Anat
67
,
21
53
Cumano
A.
,
Dieterlen-Lievre
F.
,
Godin
I.
(
1996
)
Lymphoid potential, probed before circulation in mouse, is restricted to caudal intraembryonic splanchnopleura.
Cell
86
,
907
916
Dieterlen-Lievre
F.
(
1975
)
On the origin of haemopoietic stem cells in the avian embryo: an experimental approach.
J. Embryol. Exp. Morphol
33
,
607
619
DiGiusto
D.
,
Chen
S.
,
Combs
J.
,
Webb
S.
,
Namikawa
R.
,
Tsukamoto
A.
,
Chen
B. P.
,
Galy
A. H. M.
(
1994
)
Human fetal bone marrow early progenitors for T, B, and myeloid cells are found exclusively in the population expressing high levels of CD34.
Blood
84
,
421
432
Galmiche
M. C.
,
Koteliansky
V. E.
,
Briere
J.
,
Herve
P.
,
Charbord
P.
(
1993
)
Stromal cells from human long-term marrow cultures are mesenchymal cells that differentiate following a vascular smooth muscle differentiation pathway.
Blood
82
,
66
76
Garcia-Porrero
J. A.
,
Godin
I. E.
,
Dieterlen-Lievre
F.
(
1995
)
Potential intraembryonic hemogenic sites at pre-liver stages in the mouse.
Anat. Embryol
192
,
427
435
Godin
I. E.
,
Garcia-Porrero
J. A.
,
Coutinho
A.
,
Dieterlen-Lievre
F.
,
Marcos
M. A.
(
1993
)
Para-aortic splanchnopleura from early mouse embryos contains B1a cell progenitors.
Nature
364
,
67
69
Godin
I.
,
Dieterlen-Lievre
F.
,
Cumano
A.
(
1995
)
Emergence of multipotent hemopoietic cells in the yolk sac and paraaortic splanchnopleura in mouse embryos, beginning at 8. 5 days postcoitus.
Proc. Natl. Acad. Sci. USA
92
,
773
777
Huyhn
A.
,
Dommergues
M.
,
Izac
B.
,
Croisille
L.
,
Katz
A.
,
Vainchenker
W.
,
Coulombel
L.
(
1995
)
Characterization of hematopoietic progenitors from human yolk sacs and embryos.
Blood
86
,
4474
4485
Kau
C. L.
,
Turpen
J. B.
(
1983
)
Dual contribution of embryonic ventral blood island and dorsal lateral plate mesoderm during ontogeny of hemopoietic cells in Xenopus laevis.
J. Immunol
131
,
2262
2266
Kessel
J.
,
Fabian
B. C.
(
1985
)
Graded morphogenetic patterns during the development of the extraembryonic blood system and coelom of the chick blastoderm: a scanning electron microscope and light microscope study.
Am. J. Anat
173
,
99
112
Labastie
M. C.
,
Cortes
F.
,
Romeo
P. H.
,
Dulac
C.
,
Peault
B.
(
1998
)
Molecular identity of hematopoietic precursor cells emerging in the human embryo.
Blood,
92
,
3624
3635
Lassila
O.
,
Eskola
J.
,
Toivanen
P.
,
Martin
C.
,
Dieterlen-Lievre
F.
(
1978
)
The origin of lymphoid stem cells studied in chick yolk sac-embryo chimaeras.
Nature
272
,
353
354
Maeno
M.
,
Tadate
A.
,
Katagiri
C.
(
1985
)
The localisation of precursor cells for larval and adult hematopoietic cells of Xenopus laevis in two regions of embryos.
Dev. Growth Diff
27
,
137
148
Medvinsky
A. L.
,
Samoylina
N. L.
,
Muller
A. M.
,
Dzierzak
E. A.
(
1993
)
An early pre-liver intraembryonic source of CFU-S in the developing mouse.
Nature
364
,
64
67
Medvinsky
A.
,
Dzierzak
E.
(
1996
)
Definitive hematopoiesis is autonomously initiated by the AGM region.
Cell
86
,
897
906
Migliaccio
G.
,
Migliaccio
A. R.
,
Petti
S.
,
Mavilio
F.
,
Russo
G.
,
Lazzaro
D.
,
Testa
U.
,
Marinucci
M.
,
Peschle
C.
(
1986
)
Human embryonic hemopoiesis. Kinetics of progenitors and precursors underlying the yolk sacliver transition.
J. Clin. Invest
78
,
51
60
Moore
M. A. S.
,
Owen
J. J. T.
(
1967
)
Stem cell migration in developing myeloid and lymphoid systems.
Lancet
2
,
658
659
Moore
M. A. S.
,
Metcalf
D.
(
1970
)
Ontogeny of the hematopoietic system: yolk sac origin of in vivo and in vitro colony forming cells in the developing mouse embryo.
Br. J. Haematol
18
,
279
296
Muller
A. M.
,
Medvinsky
A.
,
Strouboulis
J.
,
Grosveld
F.
,
Dzierzak
E.
(
1994
)
Development of hematopoietic stem cell activity in the mouse embryo.
Immunity
1
,
291
301
Nishikawa
S.
,
Nishikawa
S.
,
Kawamoto
H.
,
Yoshida
H.
,
Kizumoto
M.
,
Kataoka
H.
,
Katsura
Y.
(
1998
)
In vitro generation of lymphohematopoietic cells from endothelial cells purified from murine embryos.
Immunity
8
,
761
769
Ohneda
O.
,
Fennie
C.
,
Zheng
Z.
,
Donahue
C.
,
La
H.
,
Villacorta
R.
,
Cairns
B.
,
Lasky
L. A.
(
1998
)
Hematopoietic stem cell maintenance and differentiation are supported by embryonic aorta-gonad-mesonephros region-derived endothelium.
Blood
92
,
908
919
Palacios
R.
,
Imhof
B. A.
(
1996
)
Primitive lymphohematopoietic precursor cell lines generated in culture from day 7 early-mid-primitive streak stage mouse embryo.
EMBO J
15
,
6869
6876
Tavian
M.
,
Coulombel
L.
,
Luton
D.
,
San Clemente
H.
,
Dieterlen-Lievre
F.
,
Peault
B.
(
1996
)
Aorta-associated CD34+hematopoietic cells in the early human embryo.
Blood
87
,
67
72
Uchida
N.
,
Yang
Z.
,
Combs
J.
,
Pourquie
O.
,
Nguyen
M.
,
Ramanathan
R.
,
Fu
J.
,
Welply
A.
,
Chen
S.
,
Weddell
G.
,
Sharma
A. K.
,
Leiby
K. R.
,
Karagogeos
D.
,
Hill
B.
,
Humeau
L.
,
Stallcup
W. B.
,
Hoffman
R.
,
Tsukamoto
A. S.
,
Gearing
D. P.
,
Peault
B.
(
1997
)
The characterization, molecular cloning, and expression of a novel hematopoietic cell antigen from CD34+human bone marrow cells.
Blood
89
,
2706
2716
Yoder
M. C.
,
Hiatt
K.
,
Dutt
P.
,
Mukherjee
P.
,
Bodine
D. M.
,
Orlic
D.
(
1997
)
Characterization of definitive lymphohematopoeitic stem cells in the day 9 murine yolk sac.
Immunity
7
,
335
344
Young
J. C.
,
DiGiusto
D.
,
Backer
M. P.
(
1996
)
In vitro characterization of fetal hematopoietic stem cells: Range and kinetics of cell production from individual stem cells.
Biotechnology and Bioengineering
50
,
465
478
This content is only available via PDF.