激素诱导干细胞的增殖和分化

qgjin

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7 a) ~( d, I$ V* NThe pregnancy hormones human chorionic gonadotropin and progesterone induce human embryonic stem cell proliferation and differentiation into neuroectodermal rosettes。
7 Z) J* k; ]! l1 i% yMiguel J Gallego1†, Prashob Porayette1†, Maria M Kaltcheva1, Richard L Bowen2, Sivan Vadakkadath Meethal1,5,+ ~7 e- _" M8 I) ?& P- B
Craig S Atwood1,3,4*3 {5 [2 E3 l* U5 d6 @1 V

3 ^- g! t) m" Q+ C# GAbstract: l/ Q1 H1 L2 Z. `( Y
Introduction: The physiological signals that direct the division and differentiation of the zygote to form a
1 \% i& `- }* [+ o+ Fblastocyst, and subsequent embryonic stem cell division and differentiation during early embryogenesis, are
1 _$ S5 N& r6 G( X3 w- Punknown. Although a number of growth factors, including the pregnancy-associated hormone human chorionic
4 V. D7 D6 ~* W7 {0 ]' }gonadotropin (hCG) are secreted by trophoblasts that lie adjacent to the embryoblast in the blastocyst, it is not
2 b' S# d4 o0 X2 P, Xknown whether these growth factors directly signal human embryonic stem cells (hESCs).
( z& ~$ L& Q: D- ]9 H3 J  RMethods: Here we used hESCs as a model of inner cell mass differentiation to examine the hormonal requirements
% t2 u6 R# {4 gfor the formation of embryoid bodies (EB’s; akin to blastulation) and neuroectodermal rosettes (akin to neurulation).  L; G9 I1 o2 S+ m
Results: We found that hCG promotes the division of hESCs and their differentiation into EB’s and0 v  b! P+ I9 Z& |# g6 g/ i$ i
neuroectodermal rosettes. Inhibition of luteinizing hormone/chorionic gonadotropin receptor (LHCGR) signaling, @" a! L2 T. X& z
suppresses hESC proliferation, an effect that is reversed by treatment with hCG. hCG treatment rapidly upregulates
6 T: F* Q- c4 P' l7 nsteroidogenic acute regulatory protein (StAR)-mediated cholesterol transport and the synthesis of progesterone
3 v! T1 a4 K9 [(P4). hESCs express P4 receptor A, and treatment of hESC colonies with P4 induces neurulation, as demonstrated by/ w5 I# T1 f6 L
the expression of nestin and the formation of columnar neuroectodermal cells that organize into neural tubelike1 y$ ]: X( D8 y) z3 J
rosettes. Suppression of P4 signaling by withdrawing P4 or treating with the P4-receptor antagonist RU-486 inhibits
* j" o( |/ Y* ?" U! a, J6 Hthe differentiation of hESC colonies into EB’s and rosettes.) v9 w9 l5 `  S% k8 j
Conclusions: Our findings indicate that hCG signaling via LHCGR on hESC promotes proliferation and
8 m; s! N) j) W2 W) f2 Edifferentiation during blastulation and neurulation. These findings suggest that trophoblastic hCG secretion and! k& h1 d+ Z" J
signaling to the adjacent embryoblast could be the commencement of trophic support by placental tissues in the
% n" P! S! w( D0 ~9 J' @  Xgrowth and development of the human embryo.

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