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。7 e% x; g  K! x9 Q, R
Miguel J Gallego1†, Prashob Porayette1†, Maria M Kaltcheva1, Richard L Bowen2, Sivan Vadakkadath Meethal1,5,& R; G! Q* e: b# T0 }3 W; d$ S
Craig S Atwood1,3,4*
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1 Z7 R' |" d' V) T$ y/ [Abstract
( e) I7 c7 o2 Y' C# @! b5 ]$ \Introduction: The physiological signals that direct the division and differentiation of the zygote to form a6 ^/ `, w  _, A7 q6 ]
blastocyst, and subsequent embryonic stem cell division and differentiation during early embryogenesis, are
& I) |; e6 `" iunknown. Although a number of growth factors, including the pregnancy-associated hormone human chorionic
. h+ J. U. ~( D: _gonadotropin (hCG) are secreted by trophoblasts that lie adjacent to the embryoblast in the blastocyst, it is not
9 k9 k$ e1 Q9 [) O# hknown whether these growth factors directly signal human embryonic stem cells (hESCs)., T( K' a( n: o- f+ J+ k/ w; z) o
Methods: Here we used hESCs as a model of inner cell mass differentiation to examine the hormonal requirements
( Z+ M" k. I) f6 I1 s$ B' wfor the formation of embryoid bodies (EB’s; akin to blastulation) and neuroectodermal rosettes (akin to neurulation).8 E7 e. S/ e8 n* o3 U( A3 S
Results: We found that hCG promotes the division of hESCs and their differentiation into EB’s and; l% f, B. ?& R( f6 h
neuroectodermal rosettes. Inhibition of luteinizing hormone/chorionic gonadotropin receptor (LHCGR) signaling
6 G$ C! g7 ]: `( a% ksuppresses hESC proliferation, an effect that is reversed by treatment with hCG. hCG treatment rapidly upregulates
7 R8 W5 a: o, F1 {9 T' B, S* Qsteroidogenic acute regulatory protein (StAR)-mediated cholesterol transport and the synthesis of progesterone
# q. c1 y( M9 r(P4). hESCs express P4 receptor A, and treatment of hESC colonies with P4 induces neurulation, as demonstrated by
* q% w0 E( D! u: F) b& Y2 Xthe expression of nestin and the formation of columnar neuroectodermal cells that organize into neural tubelike
& F2 O6 J* R( r8 Q& Grosettes. Suppression of P4 signaling by withdrawing P4 or treating with the P4-receptor antagonist RU-486 inhibits: N: l( Y( _$ y6 X/ y7 T0 F. u
the differentiation of hESC colonies into EB’s and rosettes.) ^4 d/ v( d6 Y: P
Conclusions: Our findings indicate that hCG signaling via LHCGR on hESC promotes proliferation and" Z* [7 S! m9 L6 n$ V9 A2 d
differentiation during blastulation and neurulation. These findings suggest that trophoblastic hCG secretion and2 c6 v& e, l/ G- @
signaling to the adjacent embryoblast could be the commencement of trophic support by placental tissues in the
* j4 X5 W& i* ]9 ?0 S8 w5 Qgrowth and development of the human embryo.

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