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。+ l4 E0 w" b3 X' c
Miguel J Gallego1†, Prashob Porayette1†, Maria M Kaltcheva1, Richard L Bowen2, Sivan Vadakkadath Meethal1,5,& c' k' C) Z/ Q) U4 g- w
Craig S Atwood1,3,4*
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+ Y( G, I+ F6 wAbstract
; X# ?* \# i6 M) E/ W" A5 w$ OIntroduction: The physiological signals that direct the division and differentiation of the zygote to form a  a: I/ B0 c" ]1 E  f! U3 ~  C
blastocyst, and subsequent embryonic stem cell division and differentiation during early embryogenesis, are+ ]( e+ l2 a) g0 g
unknown. Although a number of growth factors, including the pregnancy-associated hormone human chorionic
+ }1 L; N0 Z5 i- y$ o- `( F* _gonadotropin (hCG) are secreted by trophoblasts that lie adjacent to the embryoblast in the blastocyst, it is not& L* w- K) `" X  j4 g: ]
known whether these growth factors directly signal human embryonic stem cells (hESCs).# h. a. J" j1 i0 z! y  M
Methods: Here we used hESCs as a model of inner cell mass differentiation to examine the hormonal requirements$ a; y8 `$ e% F: z) U. [/ W1 t, W8 h
for the formation of embryoid bodies (EB’s; akin to blastulation) and neuroectodermal rosettes (akin to neurulation).
$ z& D8 j' i: D6 C/ b! A7 s0 xResults: We found that hCG promotes the division of hESCs and their differentiation into EB’s and# z0 v: E6 i0 N- f
neuroectodermal rosettes. Inhibition of luteinizing hormone/chorionic gonadotropin receptor (LHCGR) signaling4 ]* V- n: c' [$ J
suppresses hESC proliferation, an effect that is reversed by treatment with hCG. hCG treatment rapidly upregulates
8 }- O/ N8 D" u9 q! w, Jsteroidogenic acute regulatory protein (StAR)-mediated cholesterol transport and the synthesis of progesterone
1 V: I3 H+ U5 V! N(P4). hESCs express P4 receptor A, and treatment of hESC colonies with P4 induces neurulation, as demonstrated by
4 m% }% T3 w; xthe expression of nestin and the formation of columnar neuroectodermal cells that organize into neural tubelike
$ Y" I$ A( G/ o" I! qrosettes. Suppression of P4 signaling by withdrawing P4 or treating with the P4-receptor antagonist RU-486 inhibits( M) a# f! ?  Y- W2 @+ a% w
the differentiation of hESC colonies into EB’s and rosettes.- ]3 u0 _% d: z: |: n4 d
Conclusions: Our findings indicate that hCG signaling via LHCGR on hESC promotes proliferation and, \) A' r2 t& V$ W
differentiation during blastulation and neurulation. These findings suggest that trophoblastic hCG secretion and
" k1 ^( d# u% O. f/ N3 lsignaling to the adjacent embryoblast could be the commencement of trophic support by placental tissues in the( U% i$ ^, S% q# w
growth and development of the human embryo.

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