激素诱导干细胞的增殖和分化

qgjin

+ A: D  ]# c6 ^/ H: K0 p

$ |. d+ P! d4 F3 p! _& e0 J
7 X2 a) H  z! z! V* rThe pregnancy hormones human chorionic gonadotropin and progesterone induce human embryonic stem cell proliferation and differentiation into neuroectodermal rosettes。4 `3 ?( n* u( ~
Miguel J Gallego1†, Prashob Porayette1†, Maria M Kaltcheva1, Richard L Bowen2, Sivan Vadakkadath Meethal1,5,
1 \- ~/ |8 |: BCraig S Atwood1,3,4*
. m5 x4 u5 F2 d' a$ c$ U6 [( J  c1 ?1 o5 Q2 I+ g7 ~6 J
Abstract
- s* g$ q: |& U5 n4 AIntroduction: The physiological signals that direct the division and differentiation of the zygote to form a
8 H$ u/ e: K9 |% T+ ublastocyst, and subsequent embryonic stem cell division and differentiation during early embryogenesis, are! B7 Y0 y  a8 T# U
unknown. Although a number of growth factors, including the pregnancy-associated hormone human chorionic  F# s7 n9 ?+ O5 L* H$ d0 `
gonadotropin (hCG) are secreted by trophoblasts that lie adjacent to the embryoblast in the blastocyst, it is not2 X& J4 o/ Z6 ~/ y: O8 A2 g' x  ^
known whether these growth factors directly signal human embryonic stem cells (hESCs).
" c9 Y& Z# q( i; v3 dMethods: Here we used hESCs as a model of inner cell mass differentiation to examine the hormonal requirements( N  j5 T; c" \# W: N. G, a
for the formation of embryoid bodies (EB’s; akin to blastulation) and neuroectodermal rosettes (akin to neurulation).
1 D% O6 F) q+ rResults: We found that hCG promotes the division of hESCs and their differentiation into EB’s and
! |3 Y! m0 a# R) Qneuroectodermal rosettes. Inhibition of luteinizing hormone/chorionic gonadotropin receptor (LHCGR) signaling  @  B6 E" v' g' b* ^, ~& C' V
suppresses hESC proliferation, an effect that is reversed by treatment with hCG. hCG treatment rapidly upregulates
& r- v8 G" l7 w# e* Hsteroidogenic acute regulatory protein (StAR)-mediated cholesterol transport and the synthesis of progesterone$ _4 k) J4 Q* I" \
(P4). hESCs express P4 receptor A, and treatment of hESC colonies with P4 induces neurulation, as demonstrated by
9 i( Z8 i: ]/ v2 Ethe expression of nestin and the formation of columnar neuroectodermal cells that organize into neural tubelike* C: G# ~& ]- w' a! e
rosettes. Suppression of P4 signaling by withdrawing P4 or treating with the P4-receptor antagonist RU-486 inhibits
% C* W& o5 \5 u% nthe differentiation of hESC colonies into EB’s and rosettes.+ r% x+ ~4 |: Q/ ~9 M6 W& x) r
Conclusions: Our findings indicate that hCG signaling via LHCGR on hESC promotes proliferation and
# y$ D$ P3 U0 ]8 _differentiation during blastulation and neurulation. These findings suggest that trophoblastic hCG secretion and
9 k5 B3 H$ }7 Ksignaling to the adjacent embryoblast could be the commencement of trophic support by placental tissues in the
3 C0 B2 s1 a0 _# I# k# cgrowth and development of the human embryo.

qingshui1985

支持一下。