Massive reorganization of the genome during primary monocyte differentiation into macrophage  

作　　者：Zhipeng Zhang Qi Wang Yulong Liu Qiu Sun Hua Li Daniel M.Czajkowsky Zhifeng Shao 

机构地区：[1]State Key Laboratory for Oncogenes and Related Genes and Bio-ID Center,School of Biom edical Engineering,Shanghai Jiao Tong University,Shanghai 200240,China [2]Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine,Shanghai East Hospital,School of Life Science and Technology,Shanghai Key Laboratory of Signaling and Disease Research,Tongji University,Shanghai 200092,China [3]Shanghai Center for Systems Biom edicine,Shanghai Jiao Tong University,Shanghai 200240,China

出　　处：《Acta Biochimica et Biophysica Sinica》2020年第5期546-553,共8页生物化学与生物物理学报（英文版）

基　　金：We thank Yani Kang from School of Biomedical Engineering.Shang-hai Jiao Tong University(Shanghai,China)for useful discussions.Thia work wal upportd by the granta from thc National Kcy R&D Program of Chima(No.2018YFC1003500),the National Natural Science Foundation of China(Nos.11374207,31501054,31670722,31900430,31971151,81627801,and 81972909),and the China Postdoctoral Science Foundation(No.2018M640419).

摘　　要：Monocyte-to-macrophage trans-differentiation has long been studied to better understand this immunological response and aspects of developmentall processes more generally.A key question is the nature of the corresponding changes in chromatin conformation and its relationship to the transcriptome during this process.This question is especially intriguing since this trans-differentiation is not associated with progression through mitosis,often considered a necessary step for gross changes in chromosomal structure.Here,we characterized the transcriptional and genomic structural changes during macrophage development of primary human monocytes using RNA-seq and in situ Hi-C.We found that,during this transition,the genome architecture undergoes a massive remodeling to a degree not observed before between structured genomes,with changes in-90%of the topologically associating domains(TADs).These changes in the TADS are associated with changed expression of immunological genes.These structural changes,however,differ extensively from those described recently in a study of the leukemia cell line,THP1.Furthermore,up-regulation of the AP.1 family of genes that ffected functionally important changes in the genomic structure during the differentiation of the THP-1 cells was not corroborated with the primary cells.Taken together,our results provide a comprehensive characterization of the changes in genomic structure during the monocyte-to-macrophage transition,establish a framework for the elucidation of processes underlying differentiation without proliferation,and demonstrate the importance of verifying with primary cells the mechanisms discovered with cultured cells.

关 键 词：cellular development contact domains genome architecture TRANS-DIFFERENTIATION 

分 类 号：Q784[生物学—分子生物学]