期刊
CELL REPORTS
卷 33, 期 10, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2020.108474
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资金
- Human Frontier Science Program Grant 2010
- European Union [686637]
- Ministerio de Ciencia e Innovacion (AEI/FEDER, UE) [BFU2017-86760-P]
- AGAUR grant from Secretaria d'Universitats i Recerca del Departament d'Empresa I Coneixement de la Generalitat de Catalunya [2017 SGR 689]
- Guangzhou Key Projects of Brain Science and Brain-Like Intelligence Technology [20200730009]
- Juan de la Cierva Fellowship
- BIST Master Fellowship
- NCI [R35CA197745]
- Spanish Ministry of Science and Innovation
- Centro de Excelencia Severo Ochoa
- CERCA Programme
- [S10OD012351]
- [S10OD021764]
Bi-species, fusion-mediated, somatic cell reprogramming allows precise, organism-specific tracking of unknown lineage drivers. The fusion of Tcf7I1(-/-) 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.
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