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

Abstract 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 t...

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Autores principales:	Yusuke Azami, Naohiro Tsuyama, Yu Abe, Misaki Sugai-Takahashi, Ken-ichi Kudo, Akinobu Ota, Karnan Sivasundaram, Moe Muramatsu, Tomonari Shigemura, Megumi Sasatani, Yuko Hashimoto, Shigehira Saji, Kenji Kamiya, Ichiro Hanamura, Takayuki Ikezoe, Masafumi Onodera, Akira Sakai
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/81747abd10d746a997909ec4057a1be8
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spelling	oai:doaj.org-article:81747abd10d746a997909ec4057a1be82021-12-02T13:20:22ZChromosomal translocation t(11;14) and p53 deletion induced by the CRISPR/Cas9 system in normal B cell-derived iPS cells10.1038/s41598-021-84628-52045-2322https://doaj.org/article/81747abd10d746a997909ec4057a1be82021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84628-5https://doaj.org/toc/2045-2322Abstract 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.Yusuke AzamiNaohiro TsuyamaYu AbeMisaki Sugai-TakahashiKen-ichi KudoAkinobu OtaKarnan SivasundaramMoe MuramatsuTomonari ShigemuraMegumi SasataniYuko HashimotoShigehira SajiKenji KamiyaIchiro HanamuraTakayuki IkezoeMasafumi OnoderaAkira SakaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yusuke Azami Naohiro Tsuyama Yu Abe Misaki Sugai-Takahashi Ken-ichi Kudo Akinobu Ota Karnan Sivasundaram Moe Muramatsu Tomonari Shigemura Megumi Sasatani Yuko Hashimoto Shigehira Saji Kenji Kamiya Ichiro Hanamura Takayuki Ikezoe Masafumi Onodera Akira Sakai Chromosomal translocation t(11;14) and p53 deletion induced by the CRISPR/Cas9 system in normal B cell-derived iPS cells
description	Abstract 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.
format	article
author	Yusuke Azami Naohiro Tsuyama Yu Abe Misaki Sugai-Takahashi Ken-ichi Kudo Akinobu Ota Karnan Sivasundaram Moe Muramatsu Tomonari Shigemura Megumi Sasatani Yuko Hashimoto Shigehira Saji Kenji Kamiya Ichiro Hanamura Takayuki Ikezoe Masafumi Onodera Akira Sakai
author_facet	Yusuke Azami Naohiro Tsuyama Yu Abe Misaki Sugai-Takahashi Ken-ichi Kudo Akinobu Ota Karnan Sivasundaram Moe Muramatsu Tomonari Shigemura Megumi Sasatani Yuko Hashimoto Shigehira Saji Kenji Kamiya Ichiro Hanamura Takayuki Ikezoe Masafumi Onodera Akira Sakai
author_sort	Yusuke Azami
title	Chromosomal translocation t(11;14) and p53 deletion induced by the CRISPR/Cas9 system in normal B cell-derived iPS cells
title_short	Chromosomal translocation t(11;14) and p53 deletion induced by the CRISPR/Cas9 system in normal B cell-derived iPS cells
title_full	Chromosomal translocation t(11;14) and p53 deletion induced by the CRISPR/Cas9 system in normal B cell-derived iPS cells
title_fullStr	Chromosomal translocation t(11;14) and p53 deletion induced by the CRISPR/Cas9 system in normal B cell-derived iPS cells
title_full_unstemmed	Chromosomal translocation t(11;14) and p53 deletion induced by the CRISPR/Cas9 system in normal B cell-derived iPS cells
title_sort	chromosomal translocation t(11;14) and p53 deletion induced by the crispr/cas9 system in normal b cell-derived ips cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/81747abd10d746a997909ec4057a1be8
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Chromosomal translocation t(11;14) and p53 deletion induced by the CRISPR/Cas9 system in normal B cell-derived iPS cells

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