Regulatory mechanisms orchestrating cellular diversity of Cd36+ olfactory sensory neurons revealed by scRNA-seq and scATAC-seq analysis.

IF 7.5 1区生物学 Q1 CELL BIOLOGY Cell reports Pub Date : 2024-08-30 DOI:10.1016/j.celrep.2024.114671

Jiawen Yang, Peiyu Shi, Yiheng Li, Yachao Zuo, Yage Nie, Tao Xu, Dongjie Peng, Ziyang An, Tingting Huang, Jingyi Zhang, Weixing Zhang, Yicong Xu, Zhongjie Tang, Anan Li, Jin Xu

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Abstract

Recent discoveries have revealed remarkable complexity within olfactory sensory neurons (OSNs), including the existence of two OSN populations based on the expression of Cd36. However, the regulatory mechanisms governing this cellular diversity in the same cell type remain elusive. Here, we show the preferential expression of 79 olfactory receptors in Cd36+ OSNs and the anterior projection characteristics of Cd36+ OSNs, indicating the non-randomness of Cd36 expression. The integrated analysis of single-cell RNA sequencing (scRNA-seq) and scATAC-seq reveals that the differences in Cd36+/- OSNs occur at the immature OSN stage, with Mef2a and Hdac9 being important regulators of developmental divergence. We hypothesize that the absence of Hdac9 may affect the activation of Mef2a, leading to the up-regulation of Mef2a target genes, including teashirt zinc finger family member 1 (Tshz1), in the Cd36+ OSN lineage. We validate that Tshz1 directly promotes Cd36 expression through enhancer bindings. Our study unravels the intricate regulatory landscape and principles governing cellular diversity in the olfactory system.

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通过 scRNA-seq 和 scATAC-seq 分析揭示协调 Cd36+ 嗅觉神经元细胞多样性的调控机制。

最近的发现揭示了嗅觉神经元（OSN）内部的显著复杂性，包括根据 Cd36 的表达存在两个 OSN 群体。然而，在同一种细胞类型中，这种细胞多样性的调控机制仍然难以捉摸。在这里，我们展示了 79 种嗅觉受体在 Cd36+ OSNs 中的优先表达以及 Cd36+ OSNs 的前投射特征，表明了 Cd36 表达的非随机性。单细胞RNA测序（scRNA-seq）和scATAC-seq的综合分析表明，Cd36+/-OSNs的差异发生在未成熟的OSN阶段，其中Mef2a和Hdac9是发育分化的重要调节因子。我们假设，Hdac9的缺失可能会影响Mef2a的激活，从而导致Mef2a靶基因（包括teashirt锌指家族成员1（Tshz1））在Cd36+/-OSN系中上调。我们验证了 Tshz1 通过增强子结合直接促进 Cd36 的表达。我们的研究揭示了嗅觉系统中错综复杂的调控格局和细胞多样性原理。

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

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.