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

Area of Science:

• Immunology
• Developmental Biology
• Molecular Biology

Background:

• B cell development is a multi-stage process where commitment to the B cell lineage is established at the pro-B cell stage.
• YY1 (Yin and Yang 1) is a pleiotropic transcription factor known for its roles in both activating and repressing gene expression.

Approach:

• Investigated the role of YY1 by creating a knockout of YY1 specifically at the pro-B cell stage.
• Assessed B cell lineage commitment using in vitro (OP9-DL4 co-culture) and in vivo (Rag1-/- mouse transplantation) models.
• Utilized single-cell RNA sequencing (scRNA-seq) to analyze transcriptomic profiles during lineage transitions.

Key Points:

• YY1 knockout in pro-B cells completely abrogates B cell lineage commitment.
• YY1-deficient pro-B cells differentiate into T lineage cells both in vitro and in vivo.
• scRNA-seq reveals significant hematopoietic lineage plasticity in YY1 knockout cells, with clusters adopting diverse lineage profiles.

Conclusions:

• YY1 is a critical regulator of B cell lineage commitment.
• The absence of YY1 confers remarkable plasticity, enabling pro-B cells to adopt alternative hematopoietic lineages, particularly T cells.
• YY1's dual function suggests a broader role in regulating cell fate decisions across multiple hematopoietic lineages.