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。
6 H7 w4 p4 U( N0 ~Miguel J Gallego1†, Prashob Porayette1†, Maria M Kaltcheva1, Richard L Bowen2, Sivan Vadakkadath Meethal1,5,
1 m9 s3 N) f/ F7 p2 Q3 _Craig S Atwood1,3,4*
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9 y9 e7 `& \3 TAbstract
- z6 O: |6 W$ }2 w4 ]( K0 r# ZIntroduction: The physiological signals that direct the division and differentiation of the zygote to form a* B2 f+ j8 \* \* K: @% u1 M) b
blastocyst, and subsequent embryonic stem cell division and differentiation during early embryogenesis, are
* u5 P/ h0 r1 gunknown. Although a number of growth factors, including the pregnancy-associated hormone human chorionic
6 ]( Q- L" \( ggonadotropin (hCG) are secreted by trophoblasts that lie adjacent to the embryoblast in the blastocyst, it is not( `6 j7 _1 _8 c6 J
known whether these growth factors directly signal human embryonic stem cells (hESCs).2 @9 C7 T6 K, _3 {% z
Methods: Here we used hESCs as a model of inner cell mass differentiation to examine the hormonal requirements
2 E& R! ^1 x: A$ G/ w7 B: r! Nfor the formation of embryoid bodies (EB’s; akin to blastulation) and neuroectodermal rosettes (akin to neurulation).7 r) ]9 r3 s) L; K! `& k$ C# L
Results: We found that hCG promotes the division of hESCs and their differentiation into EB’s and2 T: g7 ^* G6 Y+ x) S* j
neuroectodermal rosettes. Inhibition of luteinizing hormone/chorionic gonadotropin receptor (LHCGR) signaling
$ v+ c1 l1 y% E# X' Hsuppresses hESC proliferation, an effect that is reversed by treatment with hCG. hCG treatment rapidly upregulates# q- s0 c( n1 G  e4 d
steroidogenic acute regulatory protein (StAR)-mediated cholesterol transport and the synthesis of progesterone
1 _) K0 c% O) ], r(P4). hESCs express P4 receptor A, and treatment of hESC colonies with P4 induces neurulation, as demonstrated by+ \  R6 z# D+ ^
the expression of nestin and the formation of columnar neuroectodermal cells that organize into neural tubelike" e" ^2 S+ @$ V7 D1 C3 V( j
rosettes. Suppression of P4 signaling by withdrawing P4 or treating with the P4-receptor antagonist RU-486 inhibits$ t; n3 A: y( ^8 W& S- U! Q# B( |- X
the differentiation of hESC colonies into EB’s and rosettes.
* @: g$ j% d! ]" E% BConclusions: Our findings indicate that hCG signaling via LHCGR on hESC promotes proliferation and1 ?  B0 k5 B0 t; [2 v1 @
differentiation during blastulation and neurulation. These findings suggest that trophoblastic hCG secretion and
$ L' X  i. m1 ^& p% B* u1 ~( m/ a  Wsignaling to the adjacent embryoblast could be the commencement of trophic support by placental tissues in the+ l: u+ W3 }8 s7 ~
growth and development of the human embryo.

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