瑞士/瑞士法郎
生物
染色质重塑
蛋白质亚单位
细胞生物学
染色质结构重塑复合物
染色质
癌症研究
遗传学
基因
作者
Pierre Priam,Veneta Krasteva,Philippe Rousseau,Alexandre Polsinelli,Laurence Côté,Inès Desanlis,Azer Farah,Vincent‐Philippe Lavallée,Marie Kmita,Julie Lessard
标识
DOI:10.1016/j.devcel.2024.08.007
摘要
Lymphocyte development from murine hematopoietic stem cells (HSCs) entails a loss of self-renewal capacity and a progressive restriction of developmental potential. Previous research from our laboratory suggests that specialized assemblies of ATP-dependent SWI/SNF chromatin-remodeling complexes play lineage-specific roles during murine hematopoiesis. Here, we demonstrate that the Smarcd1 subunit is essential for specification of lymphoid cell fate from multipotent progenitors. Acute deletion of Smarcd1 in murine adult hematopoiesis leads to lymphopenia, characterized by a near-complete absence of early lymphoid progenitors and mature B and T cells, while the myeloid and erythroid lineages remain unaffected. Mechanistically, we demonstrate that Smarcd1 is essential for the coordinated activation of a lymphoid gene signature in murine multipotent progenitors. This is achieved by interacting with the E2a transcription factor at proximal promoters and by regulating the activity of distal enhancers. Globally, these findings identify Smarcd1 as an essential chromatin remodeler that governs lymphoid cell fate.
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