TAF4B knockdown differentially affects erythroid and natural killer cells but not monocytic differentiation from...

Hematopoietic stem and progenitor cells (HSPCs) rely on coordinated transcriptional programs, yet lineage-specific functions of general transcription machinery components remain unclear. We examined the contribution of TATA-binding protein-associated factor 4B (TAF4B) in human cord blood-derived Lin^-CD34⁺ HSPCs using shRNA-mediated knockdown across colony-forming unit (CFU) assays and directed differentiation. TAF4B knockdown reduced CFU-Mix output, whereas BFU-E and CFU-GM were unchanged. In directed erythroid culture, the proportion of CD71⁺CD235a⁺ cells was preserved, but total erythroid cell numbers and HBB transcripts decreased, while HBG and GATA1/KLF1/BCL11A mRNA remained unchanged. In monocytic differentiation, CD14⁺CD11b⁺ fractions and counts were not affected. During NK cell differentiation, CD56⁺ frequency was maintained, but the number and proportion of CD16⁺ cells declined, accompanied by reduced TBX21 with minimal change in EOMES. These findings indicate lineage- and stage-dependent sensitivity to partial TAF4B perturbation, with unresolved causality and mechanisms requiring orthogonal genetic and chromatin-focused studies.