Wolf-Hirschhorn Syndrome Candidate 1 Is Necessary for Correct Hematopoietic and B Cell Development

Publication date: 23 May 2017
Source:Cell Reports, Volume 19, Issue 8
Author(s): Elena Campos-Sanchez, Nerea Deleyto-Seldas, Veronica Dominguez, Enrique Carrillo-de-Santa-Pau, Kiyoe Ura, Pedro P. Rocha, JungHyun Kim, Arafat Aljoufi, Anna Esteve-Codina, Marc Dabad, Marta Gut, Holger Heyn, Yasufumi Kaneda, Keisuke Nimura, Jane A. Skok, Maria Luisa Martinez-Frias, Cesar Cobaleda
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.

Graphical abstract

Teaser

Campos-Sanchez et al. show that Whsc1 plays an important function in hematopoiesis in vivo, demonstrating a role for Whsc1 in the immunodeficiency in Wolf-Hirschhorn syndrome. Whsc1-deficient blood cells are impaired at several developmental stages due to defects in hematopoietic stem cell fitness and B cell lineage specification and commitment, among other problems.


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