Detail of Figure5C_iPaD_mCherryNLS
Project
Title
Fluorescence time-lapse image of iPaD-mCherryNLS expression
Description
Dentate gyrus of 11-month-old luciferase2 - Ascl1 reporter transgenic mice was injected by inducing Plagl2 and anti Dyrk1a (iPaD) - mCherryNLS lentivrus. iPaD - mCherryNLS expressed mainly at adult neural stem cells (NSCs) of dentate gyrus enhancing the proliferation of NSCs where Ascl1 supposed to express in an oscillatory manner. 4 week after iPaD lentivirus injection, brain slices containg dentate gyrus were exracted and placed in a gel supplemented by culture medium. Time-lapse imaging of the mCherry fluorescent signal derived from lentivirus infected cells were detected
Release, Updated
2024-11-25
License
CC BY
Kind
Image data
File Formats
.tif
Data size
121.0 MB
Datatype
-
Molecular Function (MF)
Biological Process (BP)
neurogenesis
(
GO:0022008
)
stem cell differentiation
(
GO:0048863
)
Cellular Component (CC)
Biological Imaging Method
X scale
-
Y scale
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Z scale
-
T scale
10 minutes per time interval
Image Acquisition
Experiment type
-
Microscope type
-
Acquisition mode
-
Contrast method
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Microscope model
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Detector model
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Objective model
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Filter set
-
Summary of Methods
See details in Kaise T, et. al. Genes Dev. 2022 Jan 1;36(1-2):23-37
Related paper(s)
Takashi Kaise, Masahiro Fukui, Risa Sueda, Wenhui Piao, Mayumi Yamada, Taeko Kobayashi, Itaru Imayoshi, Ryoichiro Kageyama (2022) Functional rejuvenation of aged neural stem cells by Plagl2 and anti-Dyrk1a activity., Genes & development, Volume 36, Number 1-2, pp. 23-37
Published in 2022 Jan 1 (Electronic publication in Dec. 16, 2021, midnight )
- doi: 10.1101/gad.349000.121
-
pmid: 34916302
(Abstract) The regenerative potential of neural stem cells (NSCs) declines during aging, leading to cognitive dysfunctions. This decline involves up-regulation of senescence-associated genes, but inactivation of such genes failed to reverse aging of hippocampal NSCs. Because many genes are up-regulated or down-regulated during aging, manipulation of single genes would be insufficient to reverse aging. Here we searched for a gene combination that can rejuvenate NSCs in the aged mouse brain from nuclear factors differentially expressed between embryonic and adult NSCs and their modulators. We found that a combination of inducing the zinc finger transcription factor gene Plagl2 and inhibiting Dyrk1a, a gene associated with Down syndrome (a genetic disorder known to accelerate aging), rejuvenated aged hippocampal NSCs, which already lost proliferative and neurogenic potential. Such rejuvenated NSCs proliferated and produced new neurons continuously at the level observed in juvenile hippocampi, leading to improved cognition. Epigenome, transcriptome, and live-imaging analyses indicated that this gene combination induces up-regulation of embryo-associated genes and down-regulation of age-associated genes by changing their chromatin accessibility, thereby rejuvenating aged dormant NSCs to function like juvenile active NSCs. Thus, aging of NSCs can be reversed to induce functional neurogenesis continuously, offering a way to treat age-related neurological disorders.(MeSH Terms)
Contact
Ryoichiro Kageyama
, RIKEN
, RIKEN Center for Brain Science
Contributors
Risa Sueda
OMERO Project
Source