Chediak-Higashi 综合征患者的 iPS 细胞可重现髓细胞中的巨大颗粒。
iPS cells from Chediak-Higashi syndrome patients recapitulate the giant granules in myeloid cells.
机构信息
Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
Department of Fundamental Cell Technologies, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
出版信息
Pediatr Int. 2022 Jan;64(1):e15390. doi: 10.1111/ped.15390.
BACKGROUND
Chediak-Higashi syndrome (CHS) is a congenital disease characterized by immunodeficiency, hemophagocytic lymphohistiocytosis, oculocutaneous albinism, and neurological symptoms. The presence of giant granules in peripheral blood leukocytes is an important hallmark of CHS. Here we prepared induced pluripotent stem cells (iPSCs) from CHS patients (CHS-iPSCs) and differentiated them into hematopoietic cells to model the disease phenotypes.
METHODS
Fibroblasts were obtained from two CHS patients and then reprogrammed into iPSCs. The iPSCs were differentiated into myeloid cells; the size of the cytosolic granules was quantified by May-Grunwald Giemsa staining and myeloperoxidase staining.
RESULTS
Two clones of iPSCs were established from each patient. The differentiation efficiency to CD33 CD45 myeloid cells was not significantly different in CHS-iPSCs compared with control iPSCs, but significantly larger granules were observed.
CONCLUSIONS
We succeeded in reproducing a characteristic cellular phenotype, giant granules in myeloid cells, using CHS-iPSCs, demonstrating that iPSCs can be used to model the pathogenesis of CHS patients.
背景
Chediak-Higashi 综合征（CHS）是一种先天性疾病，其特征为免疫缺陷、噬血细胞性淋巴组织细胞增生症、眼皮肤白化病和神经症状。外周血白细胞中存在巨大颗粒是 CHS 的重要标志。在这里，我们从 CHS 患者中制备诱导多能干细胞（iPSCs），并将其分化为造血细胞，以模拟疾病表型。
方法
从两名 CHS 患者中获得成纤维细胞，然后将其重编程为 iPSCs。将 iPSCs 分化为髓样细胞；通过 May-Grunwald Giemsa 染色和髓过氧化物酶染色来定量细胞质颗粒的大小。
结果
从每位患者均建立了两个 iPSC 克隆。与对照 iPSCs 相比，CHS-iPSCs 向 CD33 CD45 髓样细胞的分化效率没有显著差异，但观察到明显更大的颗粒。
结论
我们成功地使用 CHS-iPSCs 再现了髓样细胞中的特征性细胞表型，即巨大颗粒，表明 iPSCs 可用于模拟 CHS 患者的发病机制。
Zotero 插件