Chromosomal translocation t(11;14) and p53 deletion induced by the CRISPR/Cas9 system in normal B cell-derived iPS cells.

Autor: Azami Y; Department of Medical Oncology, Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan., Tsuyama N; Department of Radiation Life Sciences, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan., Abe Y; Department of Radiation Life Sciences, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan., Sugai-Takahashi M; Department of Radiation Life Sciences, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan., Kudo KI; Department of Radiation Life Sciences, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan., Ota A; Department of Hematology, Aichi Medical University School of Medicine, Nagakute, 480-1195, Japan., Sivasundaram K; Department of Hematology, Aichi Medical University School of Medicine, Nagakute, 480-1195, Japan., Muramatsu M; Department of Diagnostic Pathology, Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan., Shigemura T; Department of Pediatrics, Shinshu University, Matsumoto, 390-8621, Japan., Sasatani M; Department of Experimental Oncology, RIRBM, Hiroshima University, Hiroshima, 734-8553, Japan., Hashimoto Y; Department of Diagnostic Pathology, Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan., Saji S; Department of Medical Oncology, Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan., Kamiya K; Department of Experimental Oncology, RIRBM, Hiroshima University, Hiroshima, 734-8553, Japan., Hanamura I; Department of Hematology, Aichi Medical University School of Medicine, Nagakute, 480-1195, Japan., Ikezoe T; Department of Hematology, Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan., Onodera M; Department of Genetics, National Research Institute for Child Health, Development, Tokyo, 157-8535, Japan., Sakai A; Department of Radiation Life Sciences, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan. sakira@fmu.ac.jp.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Mar 04; Vol. 11 (1), pp. 5216. Date of Electronic Publication: 2021 Mar 04.
DOI: 10.1038/s41598-021-84628-5
Abstrakt: Multiple myeloma (MM) cells are derived from mature B cells based on immunoglobulin heavy chain (IgH) gene analysis. The onset of MM is often caused by a reciprocal chromosomal translocation (cTr) between chr 14 with IgH and chr 11 with CCND1. We propose that mature B cells gain potential to transform by reprograming, and then chromosomal aberrations cause the development of abnormal B cells as a myeloma-initiating cell during B cell redifferentiation. To study myeloma-initiating cells, we have already established normal B cell-derived induced pluripotent stem cells (BiPSCs). Here we established two BiPSCs with reciprocal cTr t(11;14) using the CRISPR/Cas9 system; the cleavage site were located in the IgH Eμ region of either the VDJ rearranged allele or non-rearranged allele of IgH and the 5'-upsteam region of the CCND1 (two types of BiPSC13 with t(11;14) and MIB2-6 with t(11;14)). Furthermore, p53 was deleted using the CRISPR/Cas9 system in BiPSC13 with t(11;14). These BiPSCs differentiated into hematopoietic progenitor cells (HPCs). However, unlike cord blood, those HPCs did not differentiated into B lymphocytes by co-culture with BM stromal cell. Therefore, further ingenuity is required to differentiate those BiPSCs-derived HPCs into B lymphocytes.
Databáze: MEDLINE
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