Embryonic stem (ES) cells are cells derived from the early embryo that can be propagated indefinitely in the primitive undifferentiated state while remaining pluripotent; they share these properties with embryonic germ (EG) cells. Candidate ES and EG cell lines from the human blastocyst and embryonic gonad can differentiate into multiple types of somatic cell. The phenotype of the blastocyst-derived cell lines is very similar to that of monkey ES cells and pluripotent human embryonal carcinoma cells, but differs from that of mouse ES cells or the human germ-cell-derived stem cells. Although our understanding of the control of growth and differentiation of human ES cells is quite limited, it is clear that the development of these cell lines will have a widespread impact on biomedical research.
REFERENCES
Andrews
P. W.
, Damjanov
I.
, Simon
D.
, Banting
G. S.
, Carlin
C.
, Dracopoli
N. C.
, Fogh
J.
(1984
). Pluripotent embryonal carcinoma clones derived from the human teratocarcinoma cell line Tera-2.
Lab. Invest
50
, 147
–162
Andrews
P. W.
, Casper
J.
, Damjanov
I.
, Duggan-Keen
M.
, Giwercman
A.
, Hata
J.
, von Keitz
A.
, Looijenga
L. H.
, Millan
J. L.
, Oosterhuis
J. W.
, et al. (1996
). Comparative-analysis of cell-surface antigens expressed by cell-lines derived from human germ-cell tumors.
Int. J. Cancer
66
, 806
–816
Badcock
G.
, Pigott
C.
, Goepel
J.
, Andrews
P. W.
(1999
). The human embryonal carcinoma antigen TRA-1-60 is a sialylated keratan sulphate proteoglycan.
Cancer Res
59
, 4715
–4719
Baldassarre
G.
, Romano
A.
, Armenante
F.
, Rambaldi
M.
, Paoletti
I.
, Sandomenico
C.
, Pepe
S.
, Staibano
S.
, Salvatore
G.
, de Rosa
G.
, Persico
M. G.
, Viglietto
G.
(1997
). Expression of teratocarcinoma-derived growth factor-1 (TDGF-1). in testis germ cell tumors and its effectson growth and differentiation of embryonal carcinoma cell line NTera2/D1.
Oncogene
15
, 927
–936
Brehm
A.
, Ovitt
C. E.
, Scholer
H. R.
(1998
). Oct-4: more than just a POUerful marker of the mammalian germline?.
APMIS
106
, 114
–126
Caricasole
A. A.
, van Schaik
R. H.
, Zeinstra
L. M.
, Wierikx
C. D.
, van Gurp
R. J.
, van den Pol
M.
, Looijenga
L. H.
, Oosterhuis
J. W.
, Pera
M. F.
, Ward
A.
, et al. (1998
). Human growth-differentiation factor 3 (HGDF-3)—developmental regulation in human teratocarcinoma cell lines and expression in primary testicular germ cell tumours.
Oncogene
16
, 95
–103
Cooper
S.
, Pera
M. F.
, Bennett
W.
, Finch
J. T.
(1992
). A novel keratan sulfate proteoglycan from a human embryonal carcinoma cell-line.
Biochem. J
286
, 959
–966
Dani
C.
, Chambers
I.
, Johnstone
S.
, Robertson
M.
, Ebrahimi
B.
, Saito
M.
, Taga
T.
, Li
M.
, Burdon
T.
, Nichols
J.
, Smith
A.
(1998
). Paracrine induction of stem cell renewal by LIF-deficient cells—a new ES cell regulatory pathway.
Dev. Biol
203
, 149
–162
Donovan
P. J.
(1994
). Growth-factor regulation of mouse primordial germ-cell development. Curr. Top.
Dev. Biol
29
, 189
–225
Gardner
D. K.
(1998
). Development of serum-free medium for the culture and transfer of human blastocysts.
Human Reproduction
13
, 4
–.Jorgensen
N.
, Meyts
E. R.
, Graem
N.
, Muller
J.
, Giwercman
A.
, Skakkebaek
N. E.
(1995
). Expression of immunohistochemical markers for testicular carcinoma in situ by normal human fetal germ cells.
Lab. Invest
72
, 223
–231
Kleinsmith
L. J.
, Pierce
G. B.
(1964
). Multipotentiality of single embryonal carcinoma cells.
Cancer Res
24
, 1544
–1549
Lei
W.
, Hirose
T.
, Zhang
L. X.
, Adachi
H.
, Spinella
M. J.
, Dmitrovsky
E.
, Jetten
A. M.
(1997
). Cloning of the human orphan receptor germ cell nuclear factor/retinoid receptor-related testis associated receptor and its differential regulation during embryonal carcinoma cell differentiation.
J. Mol. Endocrinol
18
, 167
–176
Li
M.
, Pevny
L.
, Lovell-Badge
R.
, Smith
A.
(1998
). Generation of purified neural precursors from embryonic stem cells by lineage selection.
Curr. Biol
8
, 971
–974
Martin
G. R.
(1980
). Teratocarcinoma and mammalian embryogenesis.
Science
209
, 768
–776
Martin
G. R.
(1981
). Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells.
Proc. Nat. Acad. Sci. USA
78
, 7634
–7638
Matsui
Y.
, Zsebo
K.
, Hogan
B. L. M.
(1992
). Derivation of pluripotential embryonic stem cells from murine primordial germ cells in culture.
Cell
70
, 841
–847
McWhir
J.
, Schnieke
A. E.
, Ansell
R.
, Wallace
H.
, Colman
A.
, Scott
A. R.
, Kind
A. J.
(1996
). Selective ablation of differentiated cells permitsisolation of embryonic stem cell lines from murine embryos with a non-permissive genetic background.
Nature Genet
14
, 223
–226
Nichols
J.
, Zevnik
B.
, Anastassiadis
K.
, Niwa
H.
, Klewenebenius
D.
, Chambers
I.
, Scholer
H.
, Smith
A.
(1998
). Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor OCT-4.
Cell
95
, 379
–391
Pera
M. F.
, Cooper
S.
, Mills
J.
, Parrington
J. M.
(1989
). Isolation and characterization of a multipotent clone of human embryonal carcinoma-cells.
Differentiation
42
, 10
–23
Rathjen
J.
, Lake
J. A.
, Bettess
M. D.
, Washington
J. M.
, Chapman
G.
, Rathjen
P. D.
(1999
). Formation of a primitive ectoderm like cell population, EPL cells, from ES cells in response to biologically derived factors.
J. Cell Sci
112
, 601
–612
Roach
S.
, Cooper
S.
, Bennett
W.
, Pera
M. F.
(1993
). Cultured cell lines from human germ cell tumours: windows into tumour growth and differentiation and early human development.
Eur. Urol
23
, 82
–88
Shamblott
M. J.
, Axelman
J.
, Wang
S. P.
, Bugg
E. M.
, Littlefield
J. W.
, Donovan
P. J.
, Blumenthal
P. D.
, Huggins
G. R.
, Gearhart
J. D.
(1998
). Derivation of pluripotent stem cells from cultured human primordial germ cells.
Proc. Nat. Acad. Sci. USA
95
, 13726
–13731
Stevens
L. C.
(1980
). Testicular, ovarian and embryo-derived teratomas.
Cancer Surveys
2
, 75
–91
Sutton
J.
, Costa
R.
, Klug
M.
, Field
L.
, Xu
D. W.
, Largaespada
D. A.
, Fletcher
C. F.
, Jenkins
N. A.
, Copeland
N. G.
, Klemsz
M.
, Hromas
R.
(1996
). Genesis, a winged helix transcriptional repressor with expression restricted to embryonic stem cells.
J. Biol. Chem
271
, 23126
–23133
Thomson
J. A.
, Kalishman
J.
, Golos
T. G.
, Durning
M.
, Harris
C. P.
, Becker
R. A.
, Hearn
J. P.
(1995
). Isolation of a primate embryonic stem-cell line.
Proc. Nat. Acad. Sci. USA
92
, 7844
–7848
Thomson
J. A.
, Kalishman
J.
, Golos
T. G.
, Durning
M.
, Harris
C. P.
, Becker
R. A.
, Hearn
J. P.
(1996
). Pluripotent cell lines derived from common marmoset (Callithrix jacchus) blastocysts.
Biol. Reprod
55
, 254
–259
Thomson
J. A.
, Marshall
V. S.
(1998
). Primate embryonic stem cells.
Curr. Topics Dev. Biol
38
, 133
–165
Thomson
J. A.
, Itskovitzeldor
J.
, Shapiro
S. S.
, Waknitz
M. A.
, Swiergiel
J. J.
, Marshall
V. S.
, Jones
J. M.
(1998
). Embryonic stem cell lines derived from human blastocysts.
Science
282
, 1145
–1147
Thompson
S.
, Stern
P. L.
, Webb
M.
, Walsh
F. S.
, Engstrom
W.
, Evans
E. P.
, Shi
W. K.
, Hopkins
B.
, Graham
C. F.
(1984
). Cloned human teratoma cells differentiate into neuron-like cells and other cell types in retinoic acid.
J. Cell Sci
72
, 37
–64
Wiles
M. V.
, Johansson
B. M.
(1999
). Embryonic stem cell development in a chemically defined medium.
Exp. Cell Res
247
, 241
–248
Xu
C. H.
, Liguori
G.
, Adamson
E. D.
, Persico
M. G.
(1998
). Specific arrest of cardiogenesis in cultured embryonic stem cells lacking Cripto-1.
Dev. Biol
196
, 237
–247
This content is only available via PDF.
© 2000 by Company of Biologists
2000
(update)-MotorCFPExtended.jpg?versionId=3964)
-bioRxiv.jpg?versionId=3964)
(update)-CSTW.png?versionId=3964)
-FocalPlaneNetwork.png?versionId=3964)
-Mole.png?versionId=3964)
