激素诱导干细胞的增殖和分化

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& q: d. k8 K. }- gThe pregnancy hormones human chorionic gonadotropin and progesterone induce human embryonic stem cell proliferation and differentiation into neuroectodermal rosettes。" F0 G. F- J% f- o
Miguel J Gallego1†, Prashob Porayette1†, Maria M Kaltcheva1, Richard L Bowen2, Sivan Vadakkadath Meethal1,5,
, o& k( k( q' p- i1 x9 UCraig S Atwood1,3,4*
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Introduction: The physiological signals that direct the division and differentiation of the zygote to form a
: P1 t" v0 ~" r* n8 B- `blastocyst, and subsequent embryonic stem cell division and differentiation during early embryogenesis, are
. X( e6 }8 A- F) ^# A! K/ T  Lunknown. Although a number of growth factors, including the pregnancy-associated hormone human chorionic5 I0 w; [7 W  Y2 t% F
gonadotropin (hCG) are secreted by trophoblasts that lie adjacent to the embryoblast in the blastocyst, it is not5 u3 ^' P2 z6 A- }  H$ M
known whether these growth factors directly signal human embryonic stem cells (hESCs).
9 @" f' K( Q, K7 `) ?Methods: Here we used hESCs as a model of inner cell mass differentiation to examine the hormonal requirements
* W. U0 N9 }; c9 {6 A- o4 Yfor the formation of embryoid bodies (EB’s; akin to blastulation) and neuroectodermal rosettes (akin to neurulation).
+ |4 y% G  b! ^3 @7 A( B+ l0 J6 TResults: We found that hCG promotes the division of hESCs and their differentiation into EB’s and/ ~" ?! }% @) Y5 H" n4 G9 _
neuroectodermal rosettes. Inhibition of luteinizing hormone/chorionic gonadotropin receptor (LHCGR) signaling6 o. C: R7 A' X
suppresses hESC proliferation, an effect that is reversed by treatment with hCG. hCG treatment rapidly upregulates
% m  S! g; V, S$ M& @" W8 usteroidogenic acute regulatory protein (StAR)-mediated cholesterol transport and the synthesis of progesterone+ @' \0 t+ y" x9 G' \" S
(P4). hESCs express P4 receptor A, and treatment of hESC colonies with P4 induces neurulation, as demonstrated by
8 v% o0 t$ Q. Z. Q" rthe expression of nestin and the formation of columnar neuroectodermal cells that organize into neural tubelike" n4 D8 r, ~4 t4 |
rosettes. Suppression of P4 signaling by withdrawing P4 or treating with the P4-receptor antagonist RU-486 inhibits4 ~8 W' E2 h) i8 F# M. E
the differentiation of hESC colonies into EB’s and rosettes.
1 A4 S; d- k/ _3 C0 Y! r/ L/ b3 j4 gConclusions: Our findings indicate that hCG signaling via LHCGR on hESC promotes proliferation and
: C9 K, V/ w6 F2 B  L2 L7 Ddifferentiation during blastulation and neurulation. These findings suggest that trophoblastic hCG secretion and1 F% @* T+ U' X: v
signaling to the adjacent embryoblast could be the commencement of trophic support by placental tissues in the- y  d( ]/ I7 r3 Y4 _, q
growth and development of the human embryo.