激素诱导干细胞的增殖和分化

qgjin

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+ B' Q1 T; R" Z3 V; U! SThe pregnancy hormones human chorionic gonadotropin and progesterone induce human embryonic stem cell proliferation and differentiation into neuroectodermal rosettes。
2 P2 Y/ w# u# k! vMiguel J Gallego1†, Prashob Porayette1†, Maria M Kaltcheva1, Richard L Bowen2, Sivan Vadakkadath Meethal1,5,  y2 K- l' Q+ n
Craig S Atwood1,3,4*4 b5 N) }8 c: w% u6 e! q# T
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Abstract- d( G$ V. ^- G1 Q
Introduction: The physiological signals that direct the division and differentiation of the zygote to form a
" ?. t9 B  b. p2 c6 Cblastocyst, and subsequent embryonic stem cell division and differentiation during early embryogenesis, are
& p# F2 j  p) O1 T% v; `unknown. Although a number of growth factors, including the pregnancy-associated hormone human chorionic
% E9 n# T! k1 Bgonadotropin (hCG) are secreted by trophoblasts that lie adjacent to the embryoblast in the blastocyst, it is not
; M0 Z: U# C! h0 U8 o% Pknown whether these growth factors directly signal human embryonic stem cells (hESCs).: {; y2 p: M9 Y8 H4 O6 H# S" ]+ n/ l
Methods: Here we used hESCs as a model of inner cell mass differentiation to examine the hormonal requirements
/ i4 E$ }/ l# cfor the formation of embryoid bodies (EB’s; akin to blastulation) and neuroectodermal rosettes (akin to neurulation).4 h' m& |' m) [, U$ L1 C1 ~* ~
Results: We found that hCG promotes the division of hESCs and their differentiation into EB’s and
" s, O4 T6 K3 J& T. e9 @+ vneuroectodermal rosettes. Inhibition of luteinizing hormone/chorionic gonadotropin receptor (LHCGR) signaling4 \8 N! O  C9 ]; L
suppresses hESC proliferation, an effect that is reversed by treatment with hCG. hCG treatment rapidly upregulates/ m8 w* F( ]7 P5 t( P# P% q) @
steroidogenic acute regulatory protein (StAR)-mediated cholesterol transport and the synthesis of progesterone' A4 `# y4 c# q+ y' m/ n( v
(P4). hESCs express P4 receptor A, and treatment of hESC colonies with P4 induces neurulation, as demonstrated by6 W" k' v* v8 t% L
the expression of nestin and the formation of columnar neuroectodermal cells that organize into neural tubelike
0 U- G$ z# \0 D# y  {' b! Y  Prosettes. Suppression of P4 signaling by withdrawing P4 or treating with the P4-receptor antagonist RU-486 inhibits
( d- C3 N" ?, j' H# A2 }) Ythe differentiation of hESC colonies into EB’s and rosettes.+ B2 v! _! Q( X6 q; E) w
Conclusions: Our findings indicate that hCG signaling via LHCGR on hESC promotes proliferation and
6 e  T2 P" g- Q: |differentiation during blastulation and neurulation. These findings suggest that trophoblastic hCG secretion and. o/ _6 Q- I/ _; |! Q  r
signaling to the adjacent embryoblast could be the commencement of trophic support by placental tissues in the5 O& T6 K- a! z! H: h% o: w
growth and development of the human embryo.

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