The master regulator protein BAZ2B can reprogram human hematopoietic lineage-committed progenitors into a multipotent state

Arumugam, Karthik; Shin, William; Schiavone, Valentina; Vlahos, Lukas; Tu, Xiaochuan; Carnevali, Davide; Kesner, Jordan; Paull, Evan O.; Romo Saladrigas, Neus, 1982-; Subramanian, Prem; Worley, Jeremy; Tan, Xiangtian; Califano, Andrea; Cosma, Maria Pia, 1970-

doi:http://dx.doi.org/10.1016/j.celrep.2020.108474

The master regulator protein BAZ2B can reprogram human hematopoietic lineage-committed progenitors into a multipotent state

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Arumugam K, Shin W, Schiavone V, Vlahos L, Tu X, Carnevali D et al. The master regulator protein BAZ2B can reprogram human hematopoietic lineage-committed progenitors into a multipotent state. Cell Rep. 2020 Dec 8; 33(10): 108474. DOI: 10.1016/j.celrep.2020.108474

Abstract

Bi-species, fusion-mediated, somatic cell reprogramming allows precise, organism-specific tracking of unknown lineage drivers. The fusion of Tcf7l1-/- murine embryonic stem cells with EBV-transformed human B cell lymphocytes, leads to the generation of bi-species heterokaryons. Human mRNA transcript profiling at multiple time points permits the tracking of the reprogramming of B cell nuclei to a multipotent state. Interrogation of a human B cell regulatory network with gene expression signatures identifies 8 candidate master regulator proteins. Of these 8 candidates, ectopic expression of BAZ2B, from the bromodomain family, efficiently reprograms hematopoietic committed progenitors into a multipotent state and significantly enhances their long-term clonogenicity, stemness, and engraftment in immunocompromised mice. Unbiased systems biology approaches let us identify the early driving events of human B cell reprogramming.