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.

中文翻译：

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pro-B 细胞中的 YY1 敲除会损害谱系定型，从而实现不寻常的造血谱系可塑性


在 B 细胞发育过程中，细胞会经历多个发育阶段，其中 pro B 细胞阶段定义了对 B 细胞谱系的承诺。YY1 是一种普遍存在的转录因子，能够同时具有激活和抑制功能。我们在这里发现，在 pro-B 细胞阶段敲除 YY1 消除了 B 谱系定型。YY1 敲除的 pro-B 细胞可以使用 OP9-DL4 饲养系统在体外产生 T 谱系细胞，并且在注射到亚致命照射的 Rag1 ^−/− 小鼠体内后产生 T 谱系细胞。这些 T 系样细胞失去其 B 系转录谱并获得 T 细胞谱系谱。单细胞 RNA-seq 实验表明，当 YY1 敲除的 pro-B 细胞在体外转变为 T 系细胞时，各种细胞簇采用代表造血谱系多样性的转录谱，表明不寻常的谱系可塑性。此外，YY1 在体内敲除 pro-B 细胞可在体内产生其他造血谱系。对 RNA-seq、scRNA-seq、ChIP-seq 和 scATAC-seq 数据的评估表明，YY1 控制着许多染色质修饰蛋白，导致 YY1 敲除 pro-B 细胞中替代谱系基因的可及性增加。鉴于 YY1 的普遍性及其双重激活和抑制功能，YY1 可能调节多个细胞谱系中的定型。