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对丝裂原活化蛋白激酶/细胞外信号调节激酶（MAPK/ERK）和骨形态发生蛋白（BMP）信号通路的双重抑制在小鼠胚胎干细胞衍生的皮质祖细胞中诱导出内嗅样特征。

Dual inhibition of MAPK/ERK and BMP signaling induces entorhinal-like identity in mouse ESC-derived pallial progenitors.

作者信息

Tonelli Fabrizio, Iannello Ludovico, Gustincich Stefano, Di Garbo Angelo, Pandolfini Luca, Cremisi Federico

机构信息

Laboratorio di Biologia, Scuola Normale Superiore, 56126 Pisa, Italy.

Istituto di Biofisica, Consiglio Nazionale delle Ricerche, 56124 Pisa, Italy.

出版信息

Stem Cell Reports. 2025 Feb 11;20(2):102387. doi: 10.1016/j.stemcr.2024.12.002. Epub 2025 Jan 9.

DOI:10.1016/j.stemcr.2024.12.002
PMID:39793576
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11864161/
Abstract

The mechanisms that determine distinct embryonic pallial identities remain elusive. The central role of Wnt signaling in directing dorsal telencephalic progenitors to the isocortex or hippocampus has been elucidated. Here, we show that timely inhibition of MAPK/ERK and BMP signaling in neuralized mouse embryonic stem cells (ESCs) specifies a cell identity characteristic of the allocortex. Comparison of the global gene expression profiles of neural cells generated by MAPK/ERK and BMP inhibition (MiBi cells) with those of cells from early postnatal encephalic regions reveals a pallial identity of MiBi cells, distinct from isocortical and hippocampal cells. MiBi cells display a unique pattern of gene expression and connectivity, and share molecular and electrophysiological features with the entorhinal cortex. Our results suggest that early changes in cell signaling can specify distinct pallial fates that are maintained by specific neuronal lineages independent of subsequent embryonic morphogenetic interactions and can determine their functional connectivity.

摘要

决定不同胚胎皮质身份的机制仍不清楚。Wnt信号在引导背侧端脑祖细胞分化为同型皮质或海马体中的核心作用已得到阐明。在此，我们表明，在神经化的小鼠胚胎干细胞（ESC）中适时抑制MAPK/ERK和BMP信号，可确定一种allocortex特有的细胞身份。将通过MAPK/ERK和BMP抑制产生的神经细胞（MiBi细胞）与出生后早期脑区细胞的全基因组表达谱进行比较，发现MiBi细胞具有皮质身份，与同型皮质和海马体细胞不同。MiBi细胞表现出独特的基因表达和连接模式，并与内嗅皮质共享分子和电生理特征。我们的结果表明，细胞信号的早期变化可以确定不同的皮质命运，这些命运由特定的神经元谱系维持，独立于随后的胚胎形态发生相互作用，并可以决定它们的功能连接。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/601f/11864161/875bbcf1cba7/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/601f/11864161/7269a74af588/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/601f/11864161/6aff28f3a25e/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/601f/11864161/ac6fa03f3a76/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/601f/11864161/489474bf37fc/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/601f/11864161/bafc1f69e8b8/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/601f/11864161/5adc79238635/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/601f/11864161/875bbcf1cba7/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/601f/11864161/7269a74af588/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/601f/11864161/6aff28f3a25e/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/601f/11864161/ac6fa03f3a76/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/601f/11864161/489474bf37fc/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/601f/11864161/bafc1f69e8b8/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/601f/11864161/5adc79238635/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/601f/11864161/875bbcf1cba7/gr6.jpg

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本文引用的文献

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Lateral entorhinal cortex subpopulations represent experiential epochs surrounding reward.
外侧缰状皮质亚群代表围绕奖励的体验时期。
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Laminin 511 and WNT signalling sustain prolonged expansion of hiPSC-derived hippocampal progenitors.层粘连蛋白 511 和 WNT 信号维持 hiPSC 来源的海马祖细胞的长期扩增。
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COUP-TFI specifies the medial entorhinal cortex identity and induces differential cell adhesion to determine the integrity of its boundary with neocortex.COUP-TFI 特异性指定内侧嗅皮层的身份，并诱导细胞间的差异黏附，以确定其与新皮层边界的完整性。
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