iPS cells from Chediak-Higashi syndrome patients recapitulate the giant granules in myeloid cells. 2022

Shigeharu Oh, and Akira Niwa, and Ayako Nagahashi, and Isao Asaka, and Tatsutoshi Nakahata, and Megumu K Saito
Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.

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.

UI MeSH Term Description Entries
D002609 Chediak-Higashi Syndrome A form of phagocyte bactericidal dysfunction characterized by unusual oculocutaneous albinism, high incidence of lymphoreticular neoplasms, and recurrent pyogenic infections. In many cell types, abnormal lysosomes are present leading to defective pigment distribution and abnormal neutrophil functions. The disease is transmitted by autosomal recessive inheritance and a similar disorder occurs in the beige mouse, the Aleutian mink, and albino Hereford cattle. Chediak-Steinbrinck-Higashi Syndrome,Oculocutaneous Albinism with Leukocyte Defect,Chediak Higashi Syndrome,Chediak Steinbrinck Higashi Syndrome,Chediak-Steinbrinck-Higashi Syndromes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D051359 Lymphohistiocytosis, Hemophagocytic A group of related disorders characterized by LYMPHOCYTOSIS; HISTIOCYTOSIS; and hemophagocytosis. The two major forms are familial and reactive. Familial Hemophagocytic Lymphocytosis,Hemophagocytic Lymphohistiocytosis, Familial,Hemophagocytic Syndrome, Infection-Associated,Hemophagocytic Syndrome, Reactive,Hemophagocytic Syndromes,Reactive Hemophagocytic Syndrome,Erythrophagocytic Lymphohistiocytosis, Familial,Familial Erythrophagocytic Lymphohistiocytosis,Familial Hemophagocytic Histiocytosis,Familial Hemophagocytic Lymphohistiocytosis,Familial Hemophagocytic Reticulosis,Familial Histiocytic Reticulosis,Hemophagocytic Lymphohistiocytosis Familial -1,Hemophagocytic Lymphohistiocytosis, Familial, 1,Hemophagocytic Reticulosis, Familial,Hemophagocytic Syndrome,Primary Hemophagocytic Hymphohistiocytosis,Primary Hemophagocytic Lymphohistiocytosis,Reticulosis, Familial Histiocytic,Erythrophagocytic Lymphohistiocytoses, Familial,Familial Erythrophagocytic Lymphohistiocytoses,Familial Hemophagocytic Histiocytoses,Familial Hemophagocytic Lymphocytoses,Familial Hemophagocytic Lymphohistiocytoses,Familial Hemophagocytic Reticuloses,Familial Histiocytic Reticuloses,Hemophagocytic Histiocytoses, Familial,Hemophagocytic Histiocytosis, Familial,Hemophagocytic Hymphohistiocytoses, Primary,Hemophagocytic Hymphohistiocytosis, Primary,Hemophagocytic Lymphocytoses, Familial,Hemophagocytic Lymphocytosis, Familial,Hemophagocytic Lymphohistiocytoses,Hemophagocytic Lymphohistiocytoses, Familial,Hemophagocytic Lymphohistiocytoses, Primary,Hemophagocytic Lymphohistiocytosis,Hemophagocytic Lymphohistiocytosis Familial 1,Hemophagocytic Lymphohistiocytosis, Primary,Hemophagocytic Reticuloses, Familial,Hemophagocytic Syndrome, Infection Associated,Histiocytic Reticuloses, Familial,Histiocytic Reticulosis, Familial,Histiocytoses, Familial Hemophagocytic,Histiocytosis, Familial Hemophagocytic,Hymphohistiocytoses, Primary Hemophagocytic,Hymphohistiocytosis, Primary Hemophagocytic,Infection-Associated Hemophagocytic Syndrome,Lymphocytoses, Familial Hemophagocytic,Lymphocytosis, Familial Hemophagocytic,Lymphohistiocytoses, Familial Erythrophagocytic,Lymphohistiocytoses, Familial Hemophagocytic,Lymphohistiocytoses, Hemophagocytic,Lymphohistiocytoses, Primary Hemophagocytic,Lymphohistiocytosis, Familial Erythrophagocytic,Lymphohistiocytosis, Familial Hemophagocytic,Lymphohistiocytosis, Primary Hemophagocytic,Primary Hemophagocytic Hymphohistiocytoses,Primary Hemophagocytic Lymphohistiocytoses,Reticuloses, Familial Hemophagocytic,Reticuloses, Familial Histiocytic,Reticulosis, Familial Hemophagocytic
D057026 Induced Pluripotent Stem Cells Cells from adult organisms that have been reprogrammed into a pluripotential state similar to that of EMBRYONIC STEM CELLS. Human Induced Pluripotent Stem Cell,IPS Cell,IPS Cells,Induced Pluripotent Stem Cell,Fibroblast-Derived IPS Cells,Fibroblast-Derived Induced Pluripotent Stem Cells,Human Induced Pluripotent Stem Cells,hiPSC,Cell, Fibroblast-Derived IPS,Cell, IPS,Cells, Fibroblast-Derived IPS,Cells, IPS,Fibroblast Derived IPS Cells,Fibroblast Derived Induced Pluripotent Stem Cells,Fibroblast-Derived IPS Cell,IPS Cell, Fibroblast-Derived,IPS Cells, Fibroblast-Derived

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