激素诱导干细胞的增殖和分化

qgjin

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. m; S, o8 g- W( X: ~* cThe pregnancy hormones human chorionic gonadotropin and progesterone induce human embryonic stem cell proliferation and differentiation into neuroectodermal rosettes。
, u  \+ S- k# S* n) G7 Z9 S  XMiguel J Gallego1†, Prashob Porayette1†, Maria M Kaltcheva1, Richard L Bowen2, Sivan Vadakkadath Meethal1,5,
% g5 T: t$ K9 q7 W9 ^$ U. }9 I7 HCraig S Atwood1,3,4*
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/ v% b- W/ U" ZAbstract
7 z; L* I, u3 L3 Y+ P3 KIntroduction: The physiological signals that direct the division and differentiation of the zygote to form a3 ~% q6 ]( |5 T6 {! H2 N
blastocyst, and subsequent embryonic stem cell division and differentiation during early embryogenesis, are
3 P' g) e4 y9 Vunknown. Although a number of growth factors, including the pregnancy-associated hormone human chorionic
' l/ ]+ {0 k* ?; Y: A0 [gonadotropin (hCG) are secreted by trophoblasts that lie adjacent to the embryoblast in the blastocyst, it is not# M5 D; _$ b# N) Q  d5 f
known whether these growth factors directly signal human embryonic stem cells (hESCs).
9 `' u* L. M: \# ]Methods: Here we used hESCs as a model of inner cell mass differentiation to examine the hormonal requirements8 W, R+ \. F+ Y
for the formation of embryoid bodies (EB’s; akin to blastulation) and neuroectodermal rosettes (akin to neurulation).
2 d# O, K" l! y) `% }Results: We found that hCG promotes the division of hESCs and their differentiation into EB’s and, Y+ d/ h6 f8 b- R0 m0 L! a
neuroectodermal rosettes. Inhibition of luteinizing hormone/chorionic gonadotropin receptor (LHCGR) signaling
% u2 f5 C' j- [6 w3 O  qsuppresses hESC proliferation, an effect that is reversed by treatment with hCG. hCG treatment rapidly upregulates4 F' z% ?! L- j2 z: k- i
steroidogenic acute regulatory protein (StAR)-mediated cholesterol transport and the synthesis of progesterone5 M6 A, E% G4 ?- m3 P
(P4). hESCs express P4 receptor A, and treatment of hESC colonies with P4 induces neurulation, as demonstrated by! e9 w3 O6 W+ F( R; H  U
the expression of nestin and the formation of columnar neuroectodermal cells that organize into neural tubelike% ?: }) A2 j7 r5 k& ?3 P) ]  h" A
rosettes. Suppression of P4 signaling by withdrawing P4 or treating with the P4-receptor antagonist RU-486 inhibits
2 Y, e& C( @2 Fthe differentiation of hESC colonies into EB’s and rosettes.
5 U% y# u: O- O( d/ H7 ]+ OConclusions: Our findings indicate that hCG signaling via LHCGR on hESC promotes proliferation and
4 X7 @+ y# E" L; w0 Bdifferentiation during blastulation and neurulation. These findings suggest that trophoblastic hCG secretion and) A: h5 J" X+ I# v" `
signaling to the adjacent embryoblast could be the commencement of trophic support by placental tissues in the! @+ i. R* s+ ?1 x, G2 X
growth and development of the human embryo.

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