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

IF 5.9 2区医学 Q1 CELL & TISSUE ENGINEERING

Stem Cell Reports Pub Date : 2024-12-31 DOI:10.1016/j.stemcr.2024.12.002

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

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引用次数: 0

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.

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MAPK/ERK和BMP信号的双重抑制诱导小鼠esc来源的苍白祖细胞的内嗅样身份。

决定不同胚胎白质身份的机制仍然难以捉摸。Wnt信号传导在引导背端远端祖细胞到达同皮层或海马中的核心作用已被阐明。本研究表明，在神经化小鼠胚胎干细胞（ESCs）中，MAPK/ERK和BMP信号的及时抑制指定了异位皮质的细胞身份特征。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整体基因表达谱的比较揭示了MiBi细胞的pallial特性，不同于等皮质细胞和海马细胞。MiBi细胞表现出独特的基因表达和连接模式，并与内嗅皮层共享分子和电生理特征。我们的研究结果表明，细胞信号的早期变化可以指定不同的pallial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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY

CiteScore

10.50

自引率

1.70%

发文量

200

审稿时长

28 weeks

期刊介绍： Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.