Single-cell analysis of transcription factor regulatory networks reveals molecular basis for subtype-specific dysregulation in acute myeloid leukemia
Single-cell analysis of transcription factor regulatory networks reveals molecular basis for subtype-specific dysregulation in acute myeloid leukemia作者机构：State Key Laboratory of Experimental HematologyNational Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjinChina Center for Stem Cell Medicine and Department of Stem Cell&Regenerative MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjinChina
出 版 物：《Blood Science》 (血液科学（英文）)
年 卷 期：2022年第4卷第2期
页 面：65-75页
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：This work was supported by grants from the National Key Research and Development Program of China(2018YFA0107804) the National Natural Science Foundation of China(81900117,82131430173) the CAMS Initiative for Innovative Medicine(2021-I2M-1–040).
主 题：Acute myeloid leukaemia Co-expression analysis Single-cell RNA-sequencing Transcription factor Transcriptional regulatory network
摘 要：Highly heterogeneous acute myeloid leukemia(AML)exhibits dysregulated transcriptional programs.Transcription factor(TF)regulatory networks underlying AML subtypes have not been elucidated at single-cell resolution.Here,we comprehensively mapped malignancy-related TFs activated in different AML subtypes by analyzing single-cell RNA sequencing data from AMLs and healthy donors.We first identified six modules of regulatory networks which were prevalently dysregulated in all AML patients.AML subtypes featured with different malignant cellular composition possessed subtype-specific regulatory TFs associated with differentiation suppression or immune modulation.At last,we validated that ERF was crucial for the development of hematopoietic stem/progenitor cells by performing loss-and gain-of-function experiments in zebrafish embryos.Collectively,our work thoroughly documents an abnormal spectrum of transcriptional regulatory networks in AML and reveals subtype-specific dysregulation basis,which provides a prospective view to AML pathogenesis and potential targets for both diagnosis and therapy.
维普期刊数据库