The pregnancy hormones human chorionic gonadotropin and progesterone induce human embryonic stem cell proliferation and differentiation into neuroectodermal rosettes.
The pregnancy hormones human chorionic gonadotropin and progesterone induce human embryonic stem cell proliferation and differentiation into neuroectodermal rosettes.
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DOI：
10.1186/scrt28
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发表时间：
2010-09-13
影响因子：
7.5
通讯作者：
Atwood CS
中科院分区：
文献类型：
--
作者：
Gallego MJ;Porayette P;Kaltcheva MM;Bowen RL;Vadakkadath Meethal S;Atwood CS
指导受精卵分裂和分化以形成胚泡的生理信号以及随后的胚胎干细胞在早期胚胎发生期间的分裂和分化是未知的。尽管许多生长因子，包括妊娠相关激素人绒毛膜促性腺激素（hCG），由位于胚泡中的胚胎母细胞附近的滋养层分泌，但尚不知道这些生长因子是否直接向人胚胎干细胞（hESC）发出信号。在这里，我们使用人胚胎干细胞作为内细胞团分化的模型，以检查形成胚状体（EB的，类似于囊胚形成）和神经外胚层roximation（类似于神经形成）的激素要求。我们发现hCG促进hESC的分裂和它们向EB和神经外胚层分化。抑制促黄体生成素/绒毛膜促性腺激素受体（LHCGR）信号传导抑制hESC增殖，这一作用可通过hCG治疗逆转。hCG治疗迅速上调类固醇生成急性调节蛋白（星星）介导的胆固醇转运和孕酮（P4）的合成。hESC表达P4受体A，用P4处理hESC集落诱导神经形成，如巢蛋白的表达和组织成神经管样神经外胚层的柱状神经外胚层细胞的形成所证明的。通过撤回P4或用P4受体拮抗剂RU-486处理来抑制P4信号传导可抑制hESC集落分化为EB和roximal。我们的研究结果表明，hCG信号通过LHCGR对人胚胎干细胞促进增殖和分化过程中的囊胚和神经形成。这些发现表明，滋养层细胞分泌hCG和信号传导到相邻的胚胎细胞可能是胎盘组织在人胚胎生长和发育中营养支持的开始。
The physiological signals that direct the division and differentiation of the zygote to form a blastocyst, and subsequent embryonic stem cell division and differentiation during early embryogenesis, are unknown. Although a number of growth factors, including the pregnancy-associated hormone human chorionic gonadotropin (hCG) are secreted by trophoblasts that lie adjacent to the embryoblast in the blastocyst, it is not known whether these growth factors directly signal human embryonic stem cells (hESCs). Here we used hESCs as a model of inner cell mass differentiation to examine the hormonal requirements for the formation of embryoid bodies (EB's; akin to blastulation) and neuroectodermal rosettes (akin to neurulation). We found that hCG promotes the division of hESCs and their differentiation into EB's and neuroectodermal rosettes. Inhibition of luteinizing hormone/chorionic gonadotropin receptor (LHCGR) signaling suppresses hESC proliferation, an effect that is reversed by treatment with hCG. hCG treatment rapidly upregulates steroidogenic acute regulatory protein (StAR)-mediated cholesterol transport and the synthesis of progesterone (P4). hESCs express P4 receptor A, and treatment of hESC colonies with P4 induces neurulation, as demonstrated by the expression of nestin and the formation of columnar neuroectodermal cells that organize into neural tubelike rosettes. Suppression of P4 signaling by withdrawing P4 or treating with the P4-receptor antagonist RU-486 inhibits the differentiation of hESC colonies into EB's and rosettes. Our findings indicate that hCG signaling via LHCGR on hESC promotes proliferation and differentiation during blastulation and neurulation. These findings suggest that trophoblastic hCG secretion and signaling to the adjacent embryoblast could be the commencement of trophic support by placental tissues in the growth and development of the human embryo.
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影响因子：
4.7
作者：
Cole, Laurence A.;Dai, Donghai;Kohorn, Ernest I.
通讯作者：
Kohorn, Ernest I.
影响因子：
2.9
作者：
Heikinheimo, O;Kekkonen, R;Lähteenmäki, P
通讯作者：
Lähteenmäki, P
影响因子：
3.6
作者：
Cutler, Sarah M.;VanLandingham, Jacob W.;Stein, Donald G.
通讯作者：
Stein, Donald G.
DOI：
10.1016/0002-9378(76)90518-4
发表时间：
1976-01-01
影响因子：
9.8
作者：
BRAUNSTEIN, GD;RASOR, J;WADE, ME
通讯作者：
WADE, ME
影响因子：
4.8
作者：
Gerami-Naini, B;Dovzhenko, OV;Golos, TG
通讯作者：
Golos, TG