| 1. |
- Dahlin, JS, et al.
(författare)
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A single-cell hematopoietic landscape resolves 8 lineage trajectories and defects in Kit mutant mice
- 2018
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 131:21, s. E1-E11
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Tidskriftsartikel (refereegranskat)abstract
- Single-cell transcriptional landscape of 44 802 hematopoietic stem/progenitor cells defines entry points to 8 different blood lineages. Comparison with 13 815 c-Kit mutant cells identifies pleiotropic changes in cell type abundance and underlying molecular profiles.
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| 2. |
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| 3. |
- Loughran, SJ, et al.
(författare)
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Mbd3/NuRD controls lymphoid cell fate and inhibits tumorigenesis by repressing a B cell transcriptional program
- 2017
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 214:10, s. 3085-3104
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Tidskriftsartikel (refereegranskat)abstract
- Differentiation of lineage-committed cells from multipotent progenitors requires the establishment of accessible chromatin at lineage-specific transcriptional enhancers and promoters, which is mediated by pioneer transcription factors that recruit activating chromatin remodeling complexes. Here we show that the Mbd3/nucleosome remodeling and deacetylation (NuRD) chromatin remodeling complex opposes this transcriptional pioneering during B cell programming of multipotent lymphoid progenitors by restricting chromatin accessibility at B cell enhancers and promoters. Mbd3/NuRD-deficient lymphoid progenitors therefore prematurely activate a B cell transcriptional program and are biased toward overproduction of pro–B cells at the expense of T cell progenitors. The striking reduction in early thymic T cell progenitors results in compensatory hyperproliferation of immature thymocytes and development of T cell lymphoma. Our results reveal that Mbd3/NuRD can regulate multilineage differentiation by constraining the activation of dormant lineage-specific enhancers and promoters. In this way, Mbd3/NuRD protects the multipotency of lymphoid progenitors, preventing B cell–programming transcription factors from prematurely enacting lineage commitment. Mbd3/NuRD therefore controls the fate of lymphoid progenitors, ensuring appropriate production of lineage-committed progeny and suppressing tumor formation.
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