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糖原合酶激酶 3（GSK3）抑制剂 SB-216763 促进小鼠胚胎干细胞的多能性。

Glycogen synthase kinase 3 (GSK3) inhibitor, SB-216763, promotes pluripotency in mouse embryonic stem cells.

机构信息

Department of Biological Science, California State University-Fullerton, Fullerton, California, United States of America.

出版信息

PLoS One. 2012;7(6):e39329. doi: 10.1371/journal.pone.0039329. Epub 2012 Jun 26.

DOI:10.1371/journal.pone.0039329
PMID:22745733
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3383737/
Abstract

Canonical Wnt/β-catenin signaling has been suggested to promote self-renewal of pluripotent mouse and human embryonic stem cells. Here, we show that SB-216763, a glycogen synthase kinase-3 (GSK3) inhibitor, can maintain mouse embryonic stem cells (mESCs) in a pluripotent state in the absence of exogenous leukemia inhibitory factor (LIF) when cultured on mouse embryonic fibroblasts (MEFs). MESCs maintained with SB-216763 for one month were morphologically indistinguishable from LIF-treated mESCs and expressed pluripotent-specific genes Oct4, Sox2, and Nanog. Furthermore, Nanog immunostaining was more homogenous in SB-216763-treated colonies compared to LIF. Embryoid bodies (EBs) prepared from these mESCs expressed early-stage markers for all three germ layers, and could efficiently differentiate into cardiac-like cells and MAP2-immunoreactive neurons. To our knowledge, SB-216763 is the first GSK3 inhibitor that can promote self-renewal of mESC co-cultured with MEFs for more than two months.

摘要

经典 Wnt/β-catenin 信号通路被认为能促进多能性的鼠类和人类胚胎干细胞的自我更新。在这里，我们发现当在鼠胚胎成纤维细胞（MEFs）上培养时，糖原合酶激酶-3（GSK3）抑制剂 SB-216763 能在没有外源性白血病抑制因子（LIF）的情况下维持鼠胚胎干细胞（mESCs）的多能性状态。用 SB-216763 培养一个月的 mESCs 在形态上与用 LIF 处理的 mESCs 没有区别，并且表达多能性特异性基因 Oct4、Sox2 和 Nanog。此外，与 LIF 相比，SB-216763 处理的集落中的 Nanog 免疫染色更为均匀。这些 mESCs 制备的类胚体（EBs）表达了三个胚层的早期标志物，并且能够有效地分化为心肌样细胞和 MAP2-免疫反应性神经元。据我们所知，SB-216763 是第一个能够促进与 MEFs 共培养的 mESC 自我更新超过两个月的 GSK3 抑制剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fb8/3383737/3ef298c08cba/pone.0039329.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fb8/3383737/02fb3e8c7bde/pone.0039329.g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fb8/3383737/1a93966eae62/pone.0039329.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fb8/3383737/db4f07aceb9b/pone.0039329.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fb8/3383737/33c9dab66149/pone.0039329.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fb8/3383737/3ef298c08cba/pone.0039329.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fb8/3383737/02fb3e8c7bde/pone.0039329.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fb8/3383737/dbbb2fc942cb/pone.0039329.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fb8/3383737/377f6fa3827c/pone.0039329.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fb8/3383737/c8c721118041/pone.0039329.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fb8/3383737/1a93966eae62/pone.0039329.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fb8/3383737/db4f07aceb9b/pone.0039329.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fb8/3383737/33c9dab66149/pone.0039329.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fb8/3383737/3ef298c08cba/pone.0039329.g008.jpg

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