Single-nucleus multi-omics identifies shared and distinct pathways in Pick’s and Alzheimer’s disease

The study of neurodegenerative diseases, particularly tauopathies like Pick’s disease (PiD) and Alzheimer’s disease (AD), offers insights into the underlying regulatory mechanisms. By investigating transcriptomic and epigenomic variations in these conditions, we identified critical regulatory changes driving disease progression, revealing potential therapeutic targets. Our comparative analyses uncovered disease-enriched non-coding regions and genome-wide transcription factor (TF) binding differences, linking them to target genes. Notably, we identified a distal human-gained enhancer (HGE) associated with E3 ubiquitin ligase (UBE3A), highlighting disease-specific regulatory alterations. Additionally, fine-mapping of AD risk genes uncovered loci enriched in microglial enhancers and accessible in other cell types. Shared and distinct TF binding patterns were observed in neurons and glial cells across PiD and AD. We validated our findings using CRISPR to excise a predicted enhancer region i..., , , # Single-nucleus multi-omics identifies shared and distinct pathways in Pick’s and Alzheimer’s disease

[https://doi.org/10.5061/dryad.h9w0vt4t9](https://doi.org/10.5061/dryad.h9w0vt4t9)

## Description of the data and file structure

| Tab | Information |
| :------- | :------------------------------------------------------------------------------------------------------ |
| tableS1A | metadata for PiD and AD  |
| tableS1B | snATAC-seq FindAllMarkers on Gene Activity  |
| tableS1C | cell counts for each celltype in snATAC-seq and snRNA-seq |
| tableS1D | snRNA-seq FindAllMarkers on Gene Expression  |
| tableS2A | a complete peakset of snATAC-seq for bo..., All human tissue samples used in this study were obtained from brain banks with appropriate institutional ethical approval and informed consent from donors or their legal representatives. Consent included permission for de-identified data to be shared publicly.

To ensure compliance with data protection policies, all personally identifiable information (PII) has been removed. Metadata fields that could potentially be used to identify individuals—such as Brainbank name, exact Age, Sample ID, and Postmortem Interval (PMI)—have been masked or anonymized in the accompanying metadata and README file.

This dataset contains only de-identified data and is shared in accordance with the ethical standards of the contributing institutions and the data sharing policy of DataDryad.org.

神经退行性疾病的研究，尤其是Pick病（PiD）与阿尔茨海默病（AD）这类tau蛋白病（tauopathies），可为阐明其潜在调控机制提供关键视角。通过探究此类疾病的转录组与表观基因组变异，本研究鉴定出驱动疾病进展的核心调控改变，揭示了潜在治疗靶点。我们的比较分析发现了疾病富集的非编码区域以及全基因组转录因子（transcription factor, TF）结合差异，并将其与靶基因建立关联。值得注意的是，我们鉴定出一个与E3泛素连接酶（E3 ubiquitin ligase, UBE3A）相关的人类特异性远端增强子（human-gained enhancer, HGE），凸显了疾病特异性的调控改变。此外，对AD风险基因的精细定位发现，其位点富集于小胶质细胞增强子区域，并在其他细胞类型中呈现染色质开放状态。在PiD与AD的神经元及神经胶质细胞中，观察到了共有的与独特的转录因子结合模式。我们通过成簇规律间隔短回文重复序列（CRISPR）技术切除预测的增强子区域以验证研究发现[原文截断]。
# 单细胞核多组学鉴定Pick病与阿尔茨海默病中共有的与独特的通路
DOI：https://doi.org/10.5061/dryad.h9w0vt4t9

## 数据与文件结构说明
| 表格编号 | 信息详情 |
| :------- | :----------------------------------------------------------------------- |
| tableS1A | PiD与AD的元数据 |
| tableS1B | 基于基因活性的单细胞核转座酶可及性测序（snATAC-seq）的FindAllMarkers分析结果 |
| tableS1C | 单细胞核转座酶可及性测序（snATAC-seq）与单细胞核RNA测序（snRNA-seq）各细胞类型的细胞计数 |
| tableS1D | 基于基因表达的单细胞核RNA测序（snRNA-seq）的FindAllMarkers分析结果 |
| tableS2A | 针对单细胞核转座酶可及性测序（snATAC-seq）的完整峰集[原文截断] |

本研究所有人体组织样本均取自脑库，已获得相应机构的伦理审查批准，并获得供体或其法定代理人的知情同意。同意书明确允许公开共享去标识化后的研究数据。

为符合数据保护政策要求，所有个人可识别信息（PII）均已完成移除。元数据字段中可能用于识别个体的信息——如脑库名称、供体精确年龄、样本ID及死后间隔时间（PMI）——已在配套元数据文件与README文档中进行掩码或匿名化处理。

本数据集仅包含去标识化后的研究数据，其共享流程符合贡献机构的伦理标准以及DataDryad.org的数据共享政策。