调控网络重构揭示急性髓系白血病细胞群体的调控特征
Network Regulatory Rewiring Characterizes AML Cell Populations
DOI: 10.12677/hjbm.2026.163060, PDF,    国家自然科学基金支持
作者: 叶一帆*, 卢 婷*, 赵 哲, 莫少康, 高瀛岱#, 颜光玗#：中国医学科学院血液病医院(中国医学科学院血液学研究所)，血液与健康全国重点实验室，国家血液系统疾病临床医学研究中心，细胞生态海河实验室，天津医学健康研究院，天津
关键词: 急性髓系白血病；染色质可及性；基因调控网络；转录因子活性；Acute Myeloid Leukemia； Chromatin Accessibility； Gene Regulatory Networks； Transcription Factor Activity
摘要: 急性髓系白血病(acute myeloid leukemia, AML)由具有干细胞样和原始细胞样特征的不同细胞群体构成，但这些细胞群体之间差异的调控基础仍未得到充分阐明。在本研究中，我们整合了公开发表的群体水平(bulk)染色质可及性数据和基因表达数据，涵盖前白血病造血干细胞(preleukemic hematopoietic stem cells, pHSC)、白血病干细胞(leukemia stem cells, LSC)以及AML原始细胞(AML blast)群体，从而系统比较了染色质可及性、预测的转录因子(transcription factor, TF)活性以及转录因子–靶基因(TF-target gene, TF-TG)的调控连接模式。研究结果表明，不同细胞群体在全局染色质可及性及转录因子组成层面总体上高度共享，而差异性可及性主要富集于远端调控元件。与此同时，转录因子活性呈现出具有结构性的、细胞群体偏倚的变化模式，而非整体一致的变化。更为重要的是，调控网络分析揭示，在转录因子身份相对保守的情况下，转录因子–靶基因调控连接模式发生了广泛改变，并在调控相互作用层面表现出显著分化和重构。综合上述多层次分析结果，本研究支持如下模型：基于这些细胞群体所推断的AML相关细胞状态之间的调控差异，主要来源于转录因子–靶基因调控连接的重构，而非转录因子组成的更替。总体而言，本研究为理解AML细胞群体间的调控组织方式及其变异提供了一个系统性的分析框架。
Abstract: Acute myeloid leukemia (AML) comprises coexisting stem-like and blast-like cell populations, yet the regulatory basis underlying their differences remains incompletely understood. In this study, we integrated publicly available bulk chromatin accessibility and gene expression datasets across preleukemic hematopoietic stem cells, leukemia stem cells, and AML blast populations to systematically compare chromatin accessibility, inferred transcription factor activity, and transcription factor-target gene regulatory connectivity. We found that global chromatin accessibility and transcription factor repertoires were broadly shared across populations, while differential accessibility was mainly localized to distal regulatory elements. In parallel, transcription factor activity exhibited structured, population-biased patterns rather than uniform shifts. Importantly, regulatory network analysis revealed extensive changes in transcription factor-target gene connectivity, with substantial divergence at the level of regulatory interactions despite relative conservation of transcription factor identity. Together, these multi-layer analyses support a model in which regulatory variation across AML-related cell states inferred from these populations is more strongly associated with reorganization of TF-target regulatory connectivity than with replacement of transcription factor composition. Overall, this study provides a systematic framework for understanding regulatory organization and its variation across AML cell populations.
文章引用：叶一帆, 卢婷, 赵哲, 莫少康, 高瀛岱, 颜光玗. 调控网络重构揭示急性髓系白血病细胞群体的调控特征[J]. 生物医学, 2026, 16(3): 576-597. https://doi.org/10.12677/hjbm.2026.163060

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