激素诱导干细胞的增殖和分化

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The pregnancy hormones human chorionic gonadotropin and progesterone induce human embryonic stem cell proliferation and differentiation into neuroectodermal rosettes。
. ?% T) ^1 B( Y2 q: k' [, fMiguel J Gallego1†, Prashob Porayette1†, Maria M Kaltcheva1, Richard L Bowen2, Sivan Vadakkadath Meethal1,5,
/ }. E: w7 M& ?9 b; HCraig S Atwood1,3,4*7 `3 \( N  g& X- e

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Introduction: The physiological signals that direct the division and differentiation of the zygote to form a
4 i. C% T. w' R3 b7 R: zblastocyst, and subsequent embryonic stem cell division and differentiation during early embryogenesis, are& ~/ t7 F  v6 @: {+ A  r3 A
unknown. Although a number of growth factors, including the pregnancy-associated hormone human chorionic) O0 `* Q1 ^% [6 {* Y' [: v  p
gonadotropin (hCG) are secreted by trophoblasts that lie adjacent to the embryoblast in the blastocyst, it is not
$ ^$ \2 h# v( d6 Tknown whether these growth factors directly signal human embryonic stem cells (hESCs).; `- h! p# V; q; l
Methods: Here we used hESCs as a model of inner cell mass differentiation to examine the hormonal requirements+ }. u3 s. Q. s+ Y
for the formation of embryoid bodies (EB’s; akin to blastulation) and neuroectodermal rosettes (akin to neurulation).5 n4 h7 j* H5 g' f
Results: We found that hCG promotes the division of hESCs and their differentiation into EB’s and
& Z9 r* ~1 i! Z' U- N$ U. Pneuroectodermal rosettes. Inhibition of luteinizing hormone/chorionic gonadotropin receptor (LHCGR) signaling, U2 q4 M" ?( y6 V( B
suppresses hESC proliferation, an effect that is reversed by treatment with hCG. hCG treatment rapidly upregulates- i3 I0 B* b# a* u: a
steroidogenic acute regulatory protein (StAR)-mediated cholesterol transport and the synthesis of progesterone
4 O) j' F; f5 p( Y9 {/ Y(P4). hESCs express P4 receptor A, and treatment of hESC colonies with P4 induces neurulation, as demonstrated by( [% M! V" a& r- {
the expression of nestin and the formation of columnar neuroectodermal cells that organize into neural tubelike  e! F0 l# Q) H: J
rosettes. Suppression of P4 signaling by withdrawing P4 or treating with the P4-receptor antagonist RU-486 inhibits# H4 N; J& Z' Y( Y
the differentiation of hESC colonies into EB’s and rosettes.
( H1 A/ P3 x( d1 t0 M( HConclusions: Our findings indicate that hCG signaling via LHCGR on hESC promotes proliferation and
; ~8 v% z7 A$ V! ddifferentiation during blastulation and neurulation. These findings suggest that trophoblastic hCG secretion and8 w8 J8 k$ }: }* D$ b) d, o  S# f
signaling to the adjacent embryoblast could be the commencement of trophic support by placental tissues in the
; Q- r/ l. `0 i0 \& U8 a3 jgrowth and development of the human embryo.