Detail of Fig2_MDS_DAC0.25_3
Project
SSBD:Repository
Title
Time-lapse images of MDS-L-2007 cells treated with 0.25 micromolar DAC
Description
Time-lapse images of MDS-L-2007 cells treated with 0.25 micromolar Decitabine. DNA was labeled with siR-DNA. Channel1; bright field, Channel2; siR-DNA
Release, Updated
2025-04-10
License
CC BY
Kind
Image data
File Formats
.tif
Data size
949.3 MB
Organism
Homo sapiens
(
NCBI:txid9606
)
Strain(s)
-
Cell Line
MDS-L-2007 (a human secondery myeloid leukemia cell line derived from an MDS (myelodysplastic syndrome) cell line, MDS-92)
Datatype
-
Molecular Function (MF)
Biological Process (BP)
cell division
,
cell cycle
Cellular Component (CC)
Biological Imaging Method
confocal microscopy
(
Fbbi:00000251
)
X scale
0.325 micrometer/pixel
Y scale
0.325 micrometer/pixel
Z scale
-
T scale
5 minutes
Image Acquisition
Experiment type
-
Microscope type
-
Acquisition mode
-
Contrast method
-
Microscope model
-
Detector model
-
Objective model
-
Filter set
-
Summary of Methods
Yabushita T, Chinen T, Nishiyama A, Asada S, Shimura R, Isobe T, Yamamoto K, Sato N, Enomoto Y, Tanaka Y, Fukuyama T, Satoh H, Kato K, Saitoh K, Ishikawa T, Soga T, Nannya Y, Fukagawa T, Nakanishi M, Kitagawa D, Kitamura T, Goyama S. Mitotic perturbation is a key mechanism of action of decitabine in myeloid tumor treatment. Cell Rep. 2023 Sep 26;42(9):113098.
Related paper(s)
Tomohiro Yabushita, Takumi Chinen, Atsuya Nishiyama, Shuhei Asada, Ruka Shimura, Tomoya Isobe, Keita Yamamoto, Naru Sato, Yutaka Enomoto, Yosuke Tanaka, Tomofusa Fukuyama, Hitoshi Satoh, Keiko Kato, Kaori Saitoh, Takamasa Ishikawa, Tomoyoshi Soga, Yasuhito Nannya, Tatsuo Fukagawa, Makoto Nakanishi, Daiju Kitagawa, Toshio Kitamura, Susumu Goyama (2023) Mitotic perturbation is a key mechanism of action of decitabine in myeloid tumor treatment., Cell reports, pp. 113098
Published in 2023 Sep 12 (Electronic publication in Sept. 12, 2023, midnight )
- doi: 10.1016/j.celrep.2023.113098
-
pmid: 37714156
(Abstract) Decitabine (DAC) is clinically used to treat myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Our genome-wide CRISPR-dCas9 activation screen using MDS-derived AML cells indicates that mitotic regulation is critical for DAC resistance. DAC strongly induces abnormal mitosis (abscission failure or tripolar mitosis) in human myeloid tumors at clinical concentrations, especially in those with TP53 mutations or antecedent hematological disorders. This DAC-induced mitotic disruption and apoptosis are significantly attenuated in DNMT1-depleted cells. In contrast, overexpression of Dnmt1, but not the catalytically inactive mutant, enhances DAC-induced mitotic defects in myeloid tumors. We also demonstrate that DAC-induced mitotic disruption is enhanced by pharmacological inhibition of the ATR-CLSPN-CHK1 pathway. These data challenge the current assumption that DAC inhibits leukemogenesis through DNMT1 inhibition and subsequent DNA hypomethylation and highlight the potent activity of DAC to disrupt mitosis through aberrant DNMT1-DNA covalent bonds.
Contact
Susumu Goyama
, The University of Tokyo
, Division of Molecular Oncology, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences
, Division of Molecular Oncology, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences
Contributors
Tomohiro Yabushita, Takumi Chinen
OMERO Project
Source