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Unusual lineage plasticity revealed by YY1 knockout in pro-B cells

Banerjee, S.; Sanyal, S.; Hodawadekar, S.; Naiyer, S.; Bano, N.; Banerjee, A.; Rhoades, J.; Dong, D.; Allman, D.; Atchison, M. L.

2024-03-27 developmental biology
10.1101/2024.03.22.586298 bioRxiv
Show 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 find 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, as well as in vivo after injection into sub-lethally 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, various cell clusters adopt transcript profiles representing a multiplicity of hematopoietic lineages indicating unusual lineage plasticity. Given the ubiquitous nature of YY1 and its dual activation and repression functions, YY1 likely regulates commitment in multiple cell lineages.

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