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 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.

Feasibility of repairing skin defects by VEGF165 gene‐modified iPS‐HFSCs seeded on a 3D printed scaffold containing astragalus polysaccharide

“…In terms of induced differentiation of extra‐embryonic cells into iPSCs, the sources can be divided into adult stem cells (bone marrow mesenchymal stem cells, 45 , 46 adipose mesenchymal stem cells 47 , 48 and hair follicle mesenchymal stem cells, 49 etc.) and adult cells (peripheral blood cells, 50 lymphocytes 51 , 52 and skin fibroblasts, 53 , 54 etc.). However, the reprogramming efficiency, induction factors, induction time of the induction medium and multi‐directional differentiation potential of adult cells can differ greatly depending on their tissue origin.…”

Stem Cells and Its Multimodality - A Review

“…Some modifications in the genetic organisation of these cells arise during the development phase from pluripotent hESCs to differentiated somatic cells. (Azami et al, 2021).…”