Sarmistha Banerjee, Sulagna Sanyal, Suchita Hodawadekar, Sarah Naiyer, Nasreen Bano, Anupam Banerjee, Joshua Rhoades, Dawei Dong, David Allman, Michael L Atchison
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引用次数: 0
Abstract
During B-cell development, cells progress through multiple developmental stages, with the pro-B-cell stage defining commitment to the B-cell lineage. YY1 is a ubiquitous transcription factor that is capable of both activation and repression functions. We found here that knockout of YY1 at the pro-B-cell stage eliminates B lineage commitment. YY1 knockout pro-B cells can generate T lineage cells in vitro using the OP9-DL4 feeder system and in vivo after injection into sublethally irradiated Rag1-/- mice. These T lineage-like cells lose their B lineage transcript profile and gain a T-cell lineage profile. Single-cell RNA-seq experiments showed that as YY1 knockout pro-B cells transition into T lineage cells in vitro, various cell clusters adopt transcript profiles representing a multiplicity of hematopoietic lineages, indicating unusual lineage plasticity. In addition, YY1 KO pro-B cells in vivo can give rise to other hematopoietic lineages in vivo. Evaluation of RNA-seq, scRNA-seq, ChIP-seq, and scATAC-seq data indicates that YY1 controls numerous chromatin-modifying proteins leading to increased accessibility of alternative lineage genes in YY1 knockout pro-B cells. Given the ubiquitous nature of YY1 and its dual activation and repression functions, YY1 may regulate commitment in multiple cell lineages.
在 B 细胞发育过程中,细胞会经历多个发育阶段,前 B 细胞阶段决定了 B 细胞系的形成。YY1是一种无处不在的转录因子,具有激活和抑制两种功能。我们在此发现,在前B细胞阶段敲除YY1可消除B细胞系的承诺。YY1基因敲除的原B细胞可在体外利用OP9-DL4馈源系统产生T系细胞,在体内注射到经亚伯辐照的Rag1-/-小鼠体内后也可产生T系细胞。这些类 T 系细胞失去了 B 系转录本特征,获得了 T 细胞系特征。单细胞RNA-seq实验显示,当YY1基因敲除的原B细胞在体外过渡到T系细胞时,不同的细胞集群采用了代表多种造血系的转录本特征,显示出不同寻常的系可塑性。此外,体内 YY1 KO 亲 B 细胞还能在体内产生其他造血系。对 RNA-seq、scRNA-seq、ChIP-seq 和 scATAC-seq 数据的评估表明,YY1 控制着大量染色质修饰蛋白,导致 YY1 基因敲除的原 B 细胞中替代系基因的可及性增加。鉴于 YY1 的无处不在性及其双重激活和抑制功能,YY1 可能调控多种细胞系的承诺。
期刊介绍:
Genes & Development is a research journal published in association with The Genetics Society. It publishes high-quality research papers in the areas of molecular biology, molecular genetics, and related fields. The journal features various research formats including Research papers, short Research Communications, and Resource/Methodology papers.
Genes & Development has gained recognition and is considered as one of the Top Five Research Journals in the field of Molecular Biology and Genetics. It has an impressive Impact Factor of 12.89. The journal is ranked #2 among Developmental Biology research journals, #5 in Genetics and Heredity, and is among the Top 20 in Cell Biology (according to ISI Journal Citation Reports®, 2021).