RRC ID 58131
Author Shimada M, Tsukada K, Kagawa N, Matsumoto Y.
Title Reprogramming and differentiation-dependent transcriptional alteration of DNA damage response and apoptosis genes in human induced pluripotent stem cells.
Journal J Radiat Res
Abstract Pluripotent stem cells (PSCs), such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have a dual capability to self-renew and differentiate into all cell types necessary to develop an entire organism. Differentiation is associated with dynamic epigenetic alteration and transcriptional change, while self-renewal depends on maintaining the genome DNA accurately. Genome stability of PSCs is strictly regulated to maintain pluripotency. However, the DNA damage response (DDR) mechanism in PSCs is still unclear. There is accumulating evidence that genome stability and pluripotency are regulated by a transcriptional change in undifferentiated and differentiated states. iPSCs are ideal for analyzing transcriptional regulation during reprogramming and differentiation. This study aimed to elucidate the transcriptional alteration surrounding genome stability maintenance, including DNA repair, cell cycle checkpoints and apoptosis in fibroblasts, iPSCs and neural progenitor cells (NPCs) derived from iPSCs as differentiated cells. After ionizing radiation exposure, foci for the DNA double-stranded break marker γ-H2AX increased, peaking at 0.5 h in all cells (>90%), decreasing after 4 h in fibroblasts (32.3%) and NPCs (22.3%), but still remaining at 52.5% (NB1RGB C2 clone) and 54.7% (201B7 cells) in iPSCs. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells were detected, indicating that iPSCs' apoptosis increases. In addition, RNA sequencing (RNA-Seq) analysis showed high expression of apoptosis genes (TP53, CASP3 and BID) in iPSCs. Results suggested that increased apoptosis activity maintains accurate, undifferentiated genome DNA in the cell population.
Volume 60(6)
Pages 719-728
Published 2019-11-22
DOI 10.1093/jrr/rrz057
PII 5607840
PMID 31665364
PMC PMC7357234
MeSH Apoptosis / genetics* Apoptosis / radiation effects Cell Differentiation / genetics* Cell Differentiation / radiation effects Cell Line Cellular Reprogramming / genetics* Cellular Reprogramming / radiation effects DNA Damage / genetics* DNA Repair / genetics DNA Repair / radiation effects Fibroblasts / cytology Fibroblasts / radiation effects Gene Expression Regulation* / radiation effects Humans Induced Pluripotent Stem Cells / cytology* Induced Pluripotent Stem Cells / metabolism* Induced Pluripotent Stem Cells / radiation effects Neural Stem Cells / cytology Neural Stem Cells / metabolism Neural Stem Cells / radiation effects Radiation, Ionizing Skin / cytology Transcription, Genetic*
IF 2.014
Times Cited 2
Human and Animal Cells NB1RGB(RCB0222)