小柯机器人

美国埃默里大学医学院Steven A. Sloan团队近期取得重要工作进展。他们研究鉴定出了驱动人类星形胶质细胞发育的配体-受体对。相关研究成果2023年7月17日在线发表于《自然—神经科学》杂志上。

据介绍，不同细胞类型之间的外源信号传导对神经系统的发育至关重要。配体结合是发育过程的关键驱动因素。然而，弄清楚哪些外源信号以及如何协同作用来影响受体细胞的变化仍然是一个重大挑战。

在发育中的人脑中，皮层祖细胞以定型的序列从神经发生转变为胶质发生，这在一定程度上受到外源配体的影响。研究人员使用已发表的转录组学数据来识别和功能测试协同驱动人类星形胶质细胞发生的五种配体-受体对。研究人员验证了TGFβ2、NLGN1、TSLP、DKK1和BMP4配体对hCO和原代胎儿组织中星形胶质细胞发育的协同作用。研究人员证实，这五个配体的合作能力大于它们的个体能力。

此外，研究人员发现它们的组合效应部分集中在mTORC1信号通路上，导致星形胶质细胞发育的转录组学和形态学特征。

总之，这一数据驱动框架可以利用单细胞和大量基因组数据来生成和测试围绕调节神经发育过程中细胞间通讯的功能假设。

附：英文原文

Title: Identification of ligand–receptor pairs that drive human astrocyte development

Author: Voss, Anna J., Lanjewar, Samantha N., Sampson, Maureen M., King, Alexia, Hill, Emily J., Sing, Anson, Sojka, Caitlin, Bhatia, Tarun N., Spangle, Jennifer M., Sloan, Steven A.

Issue&Volume: 2023-07-17

Abstract: Extrinsic signaling between diverse cell types is crucial for nervous system development. Ligand binding is a key driver of developmental processes. Nevertheless, it remains a significant challenge to disentangle which and how extrinsic signals act cooperatively to affect changes in recipient cells. In the developing human brain, cortical progenitors transition from neurogenesis to gliogenesis in a stereotyped sequence that is in part influenced by extrinsic ligands. Here we used published transcriptomic data to identify and functionally test five ligand–receptor pairs that synergistically drive human astrogenesis. We validate the synergistic contributions of TGFβ2, NLGN1, TSLP, DKK1 and BMP4 ligands on astrocyte development in both hCOs and primary fetal tissue. We confirm that the cooperative capabilities of these five ligands are greater than their individual capacities. Additionally, we discovered that their combinatorial effects converge in part on the mTORC1 signaling pathway, resulting in transcriptomic and morphological features of astrocyte development. Our data-driven framework can leverage single-cell and bulk genomic data to generate and test functional hypotheses surrounding cell–cell communication regulating neurodevelopmental processes.

DOI: 10.1038/s41593-023-01375-8

Source: https://www.nature.com/articles/s41593-023-01375-8

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex