激素诱导干细胞的增殖和分化

qgjin

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+ m' j3 N: c; m6 j* GThe pregnancy hormones human chorionic gonadotropin and progesterone induce human embryonic stem cell proliferation and differentiation into neuroectodermal rosettes。
5 Y2 R6 ^  y; IMiguel J Gallego1†, Prashob Porayette1†, Maria M Kaltcheva1, Richard L Bowen2, Sivan Vadakkadath Meethal1,5,
& V& j7 l+ k6 v5 m) O" D( }Craig S Atwood1,3,4*3 K0 h# \2 y; E( t" o+ Y

5 X; S; r" J3 m# V* A5 cAbstract/ u9 O: c6 S# w- X, J+ n9 q
Introduction: The physiological signals that direct the division and differentiation of the zygote to form a: f6 x5 Y" f( A$ H
blastocyst, and subsequent embryonic stem cell division and differentiation during early embryogenesis, are' z7 ?) ?% {. u; N7 `. K' z- C$ j: s
unknown. Although a number of growth factors, including the pregnancy-associated hormone human chorionic! f; M( y' d$ w1 B
gonadotropin (hCG) are secreted by trophoblasts that lie adjacent to the embryoblast in the blastocyst, it is not
0 O& b$ I( I8 d/ rknown whether these growth factors directly signal human embryonic stem cells (hESCs).
2 ], e& ?3 d1 {$ j1 Y" hMethods: Here we used hESCs as a model of inner cell mass differentiation to examine the hormonal requirements
; T* h: T+ _6 f4 m! Wfor the formation of embryoid bodies (EB’s; akin to blastulation) and neuroectodermal rosettes (akin to neurulation).
3 d. R; K$ T. j5 Z: g' NResults: We found that hCG promotes the division of hESCs and their differentiation into EB’s and
1 K* S/ p. J4 p6 [1 k" r7 x8 V$ v' Jneuroectodermal rosettes. Inhibition of luteinizing hormone/chorionic gonadotropin receptor (LHCGR) signaling
( r2 D9 h) K) ?. `+ W# l  W- z9 U+ Ysuppresses hESC proliferation, an effect that is reversed by treatment with hCG. hCG treatment rapidly upregulates6 E$ n$ H) ?; q% M$ V9 u8 M! S
steroidogenic acute regulatory protein (StAR)-mediated cholesterol transport and the synthesis of progesterone7 Q! V! f# y1 @
(P4). hESCs express P4 receptor A, and treatment of hESC colonies with P4 induces neurulation, as demonstrated by4 m1 p% x" i/ |9 G) x. g- n" A
the expression of nestin and the formation of columnar neuroectodermal cells that organize into neural tubelike% @  Y9 c  j- q
rosettes. Suppression of P4 signaling by withdrawing P4 or treating with the P4-receptor antagonist RU-486 inhibits2 M- G4 D4 I- Y( O, T6 O4 H8 ]/ R
the differentiation of hESC colonies into EB’s and rosettes.
; U& h. C+ C, v& q1 CConclusions: Our findings indicate that hCG signaling via LHCGR on hESC promotes proliferation and
3 @# h9 b9 a  H: A. x) vdifferentiation during blastulation and neurulation. These findings suggest that trophoblastic hCG secretion and
( n' @" H+ W+ N- Wsignaling to the adjacent embryoblast could be the commencement of trophic support by placental tissues in the5 Q# h! v( ]) ^( u. s) y
growth and development of the human embryo.

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