激素诱导干细胞的增殖和分化

qgjin

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! ^& c$ A! Q% ^6 k2 I/ z1 a8 P9 |The pregnancy hormones human chorionic gonadotropin and progesterone induce human embryonic stem cell proliferation and differentiation into neuroectodermal rosettes。6 K3 r1 [: y1 c0 f, r5 b% w
Miguel J Gallego1†, Prashob Porayette1†, Maria M Kaltcheva1, Richard L Bowen2, Sivan Vadakkadath Meethal1,5,* n/ F) \) }' @, D
Craig S Atwood1,3,4*+ Z( K& W, f& x) E

  |! ]0 ~  q2 L0 l- K% VAbstract
" a9 \5 H% Z* I& s1 W. g5 XIntroduction: The physiological signals that direct the division and differentiation of the zygote to form a
7 m- ~' H9 ?. H' `9 g1 |9 j9 {! @blastocyst, and subsequent embryonic stem cell division and differentiation during early embryogenesis, are3 }6 o, j1 h( O
unknown. Although a number of growth factors, including the pregnancy-associated hormone human chorionic/ L" o, y6 r" g* f+ k9 [
gonadotropin (hCG) are secreted by trophoblasts that lie adjacent to the embryoblast in the blastocyst, it is not7 r. y+ Q  K  H
known whether these growth factors directly signal human embryonic stem cells (hESCs).1 J' A. r/ p9 s9 c( f0 y% ^
Methods: Here we used hESCs as a model of inner cell mass differentiation to examine the hormonal requirements0 u5 A5 E$ y/ @6 N
for the formation of embryoid bodies (EB’s; akin to blastulation) and neuroectodermal rosettes (akin to neurulation).1 x" j* }, T9 M# d0 T) A5 X: g
Results: We found that hCG promotes the division of hESCs and their differentiation into EB’s and8 u; g8 G% Z7 U5 M* s
neuroectodermal rosettes. Inhibition of luteinizing hormone/chorionic gonadotropin receptor (LHCGR) signaling! @/ V8 y6 Z- u7 O" x2 M
suppresses hESC proliferation, an effect that is reversed by treatment with hCG. hCG treatment rapidly upregulates5 a" f4 \# o* y* j% A
steroidogenic acute regulatory protein (StAR)-mediated cholesterol transport and the synthesis of progesterone+ M- O; P, |  F) h& S) e: `* k
(P4). hESCs express P4 receptor A, and treatment of hESC colonies with P4 induces neurulation, as demonstrated by
* q+ I: V- ]. mthe expression of nestin and the formation of columnar neuroectodermal cells that organize into neural tubelike
- |7 _" P0 [/ N* e' Q" {rosettes. Suppression of P4 signaling by withdrawing P4 or treating with the P4-receptor antagonist RU-486 inhibits4 G0 l  q* ?) @
the differentiation of hESC colonies into EB’s and rosettes.9 N  D0 W; e7 g+ R
Conclusions: Our findings indicate that hCG signaling via LHCGR on hESC promotes proliferation and* h; d: V" N& C. f& [+ Y  R
differentiation during blastulation and neurulation. These findings suggest that trophoblastic hCG secretion and
; m9 c  V3 Q7 o- Z3 msignaling to the adjacent embryoblast could be the commencement of trophic support by placental tissues in the
6 C6 s6 B. Z( `1 x, Y' igrowth and development of the human embryo.

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