激素诱导干细胞的增殖和分化

qgjin

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; J! U' o) g# E9 }The pregnancy hormones human chorionic gonadotropin and progesterone induce human embryonic stem cell proliferation and differentiation into neuroectodermal rosettes。4 x7 ?$ Z% L* z5 ]7 F  g5 X  |
Miguel J Gallego1†, Prashob Porayette1†, Maria M Kaltcheva1, Richard L Bowen2, Sivan Vadakkadath Meethal1,5,
' O, J6 {" _7 yCraig S Atwood1,3,4*
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Abstract$ S& ^9 g1 _! i: H/ E
Introduction: The physiological signals that direct the division and differentiation of the zygote to form a
1 ]2 _; e2 {1 `% o8 ]6 J2 Pblastocyst, and subsequent embryonic stem cell division and differentiation during early embryogenesis, are5 z5 [' z" q( [  c( I) D
unknown. Although a number of growth factors, including the pregnancy-associated hormone human chorionic
, l! M: D% V( |* z" egonadotropin (hCG) are secreted by trophoblasts that lie adjacent to the embryoblast in the blastocyst, it is not
! e# @: }! h/ U  [( |known whether these growth factors directly signal human embryonic stem cells (hESCs).
( `2 D( Y. G2 qMethods: Here we used hESCs as a model of inner cell mass differentiation to examine the hormonal requirements
0 T  Z  o. }, o7 Pfor the formation of embryoid bodies (EB’s; akin to blastulation) and neuroectodermal rosettes (akin to neurulation).2 G7 X7 e; i; j
Results: We found that hCG promotes the division of hESCs and their differentiation into EB’s and7 t5 o& D: K1 J& O( |
neuroectodermal rosettes. Inhibition of luteinizing hormone/chorionic gonadotropin receptor (LHCGR) signaling
7 v& s# [0 D% Y4 k" isuppresses hESC proliferation, an effect that is reversed by treatment with hCG. hCG treatment rapidly upregulates
6 p) G  L1 A: U. ^% asteroidogenic acute regulatory protein (StAR)-mediated cholesterol transport and the synthesis of progesterone5 q/ d1 T+ B* r( C+ l2 N3 g7 N
(P4). hESCs express P4 receptor A, and treatment of hESC colonies with P4 induces neurulation, as demonstrated by$ W& v0 i- v. S% U1 Q
the expression of nestin and the formation of columnar neuroectodermal cells that organize into neural tubelike' f, C6 O& @& K. X2 z& f7 D
rosettes. Suppression of P4 signaling by withdrawing P4 or treating with the P4-receptor antagonist RU-486 inhibits
5 R0 N$ r! Q; \the differentiation of hESC colonies into EB’s and rosettes.3 i" C' E: F4 C2 L( U/ g
Conclusions: Our findings indicate that hCG signaling via LHCGR on hESC promotes proliferation and
! P$ M5 m9 U! ]. m; Q. j% {differentiation during blastulation and neurulation. These findings suggest that trophoblastic hCG secretion and; H" }5 Y& h( M) l' K
signaling to the adjacent embryoblast could be the commencement of trophic support by placental tissues in the% B3 c/ @! \% e  `& q1 K
growth and development of the human embryo.

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