激素诱导干细胞的增殖和分化

qgjin

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The pregnancy hormones human chorionic gonadotropin and progesterone induce human embryonic stem cell proliferation and differentiation into neuroectodermal rosettes。
: ?& p+ M5 y1 B4 @" U. J3 J& @. p$ ~Miguel J Gallego1†, Prashob Porayette1†, Maria M Kaltcheva1, Richard L Bowen2, Sivan Vadakkadath Meethal1,5,' X' p3 R1 M$ a
Craig S Atwood1,3,4*7 w. w( k0 W/ f- c' R  m

4 E3 o: }: Z! NAbstract2 j6 u% {- V6 l; k
Introduction: The physiological signals that direct the division and differentiation of the zygote to form a
0 u( C! B3 B2 p1 V, S1 Ablastocyst, and subsequent embryonic stem cell division and differentiation during early embryogenesis, are
: F; i  n2 u6 g% F& r7 c8 I2 N% Punknown. Although a number of growth factors, including the pregnancy-associated hormone human chorionic2 X4 \8 }, f0 ]; n9 N) R$ [
gonadotropin (hCG) are secreted by trophoblasts that lie adjacent to the embryoblast in the blastocyst, it is not( g+ N, Z# z/ r# D% ^8 k$ C9 v1 f2 n
known whether these growth factors directly signal human embryonic stem cells (hESCs).' s0 k) x$ U7 g' e' r6 R$ z4 q
Methods: Here we used hESCs as a model of inner cell mass differentiation to examine the hormonal requirements: k0 ~0 c! g$ v/ {  i9 q
for the formation of embryoid bodies (EB’s; akin to blastulation) and neuroectodermal rosettes (akin to neurulation).
' t# E  ?) J6 P. h1 y' L4 H; NResults: We found that hCG promotes the division of hESCs and their differentiation into EB’s and, @2 A  h# I# z# s
neuroectodermal rosettes. Inhibition of luteinizing hormone/chorionic gonadotropin receptor (LHCGR) signaling
3 M5 n1 b3 G& n3 ksuppresses hESC proliferation, an effect that is reversed by treatment with hCG. hCG treatment rapidly upregulates0 U. q- P$ k, G: _3 M
steroidogenic acute regulatory protein (StAR)-mediated cholesterol transport and the synthesis of progesterone! y$ {7 @3 @9 E- ^
(P4). hESCs express P4 receptor A, and treatment of hESC colonies with P4 induces neurulation, as demonstrated by3 L3 ~/ Y8 [! F) |* u, ~6 i9 ?
the expression of nestin and the formation of columnar neuroectodermal cells that organize into neural tubelike/ A6 H+ H: N5 Z/ m
rosettes. Suppression of P4 signaling by withdrawing P4 or treating with the P4-receptor antagonist RU-486 inhibits7 e' P, `" f+ c4 _8 g
the differentiation of hESC colonies into EB’s and rosettes./ W  B: w& S9 ~" E. X. _3 n& B, i
Conclusions: Our findings indicate that hCG signaling via LHCGR on hESC promotes proliferation and+ h5 f7 K* y0 z: u- E5 [) {
differentiation during blastulation and neurulation. These findings suggest that trophoblastic hCG secretion and
4 E) J/ @0 V/ V  w7 n7 o1 Tsignaling to the adjacent embryoblast could be the commencement of trophic support by placental tissues in the
' Y# S& E: U& _" ]% h5 \5 [; e/ Cgrowth and development of the human embryo.

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