| Literature DB >> 28538178 |
Elena Campos-Sanchez1, Nerea Deleyto-Seldas1, Veronica Dominguez2, Enrique Carrillo-de-Santa-Pau3, Kiyoe Ura4, Pedro P Rocha5, JungHyun Kim5, Arafat Aljoufi5, Anna Esteve-Codina6, Marc Dabad6, Marta Gut6, Holger Heyn6, Yasufumi Kaneda7, Keisuke Nimura7, Jane A Skok5, Maria Luisa Martinez-Frias8, Cesar Cobaleda9.
Abstract
Immunodeficiency is one of the most important causes of mortality associated with Wolf-Hirschhorn syndrome (WHS), a severe rare disease originated by a deletion in chromosome 4p. The WHS candidate 1 (WHSC1) gene has been proposed as one of the main genes responsible for many of the alterations in WHS, but its mechanism of action is still unknown. Here, we present in vivo genetic evidence showing that Whsc1 plays an important role at several points of hematopoietic development. Particularly, our results demonstrate that both differentiation and function of Whsc1-deficient B cells are impaired at several key developmental stages due to profound molecular defects affecting B cell lineage specification, commitment, fitness, and proliferation, demonstrating a causal role for WHSC1 in the immunodeficiency of WHS patients.Entities:
Keywords: B cell development; H3K36 methylation; Wolf-Hirschhorn syndrome; cell cycle; class-switch recombination; hematopoiesis; hematopoietic stem cells; immunodeficiency; replicative stress
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Year: 2017 PMID： 28538178 PMCID： PMC5510986 DOI： 10.1016/j.celrep.2017.04.069
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423