Wolf-Hirschhorn Syndrome Candidate 1 Is Necessary for Correct Hematopoietic and B Cell Development.
Wolf-Hirschhorn Syndrome Candidate 1 Is Necessary for Correct Hematopoietic and B Cell Development.
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DOI：
10.1016/j.celrep.2017.04.069
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发表时间：
2017-05-23
期刊：
影响因子：
8.8
通讯作者：
Cobaleda C
中科院分区：
文献类型：
--
作者：
Campos-Sanchez E;Deleyto-Seldas N;Dominguez V;Carrillo-de-Santa-Pau E;Ura K;Rocha PP;Kim J;Aljoufi A;Esteve-Codina A;Dabad M;Gut M;Heyn H;Kaneda Y;Nimura K;Skok JA;Martinez-Frias ML;Cobaleda C
免疫缺陷是与沃尔夫-赫希霍恩综合征（WHS）相关的死亡率的最重要原因之一，WHS是一种由染色体4p缺失引起的严重罕见疾病。WHS候选基因1（WHSC 1）被认为是WHS中许多改变的主要原因之一，但其作用机制仍不清楚。在这里，我们提出了体内遗传证据表明，Whsc 1在造血发育的几个点起着重要作用。特别是，我们的研究结果表明，WHSC 1缺陷的B细胞的分化和功能在几个关键的发育阶段受损，由于深刻的分子缺陷影响B细胞谱系的规范，承诺，健身和增殖，因此证明了WHSC 1在WHS患者的免疫缺陷的因果关系的作用。Campos-Sanchez等人表明，Whsc 1在体内造血中起重要作用，证明了Whsc 1在Wolf-Hirschhorn综合征中的免疫缺陷中的作用。whsc 1缺陷型血细胞在几个发育阶段由于HSC适应性和B细胞谱系特化和定型的缺陷而受损，以及其他问题。
Immunodeficiency is one of the most important causes of mortality associated to 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 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, therefore demonstrating a causal role for WHSC1 in the immunodeficiency of WHS patients. 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 HSC fitness and B cell lineage specification and commitment, among other problems.
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通讯作者：
Ceccaldi R