Generation of a Hutchinson–Gilford progeria syndrome monkey model by base editing

Wang, Fang; Zhang, Weiqi; Yang, Qiong; Kang, Yu; Fan, Yanling; Wei, Jingkuan; Liu, Zunpeng; Dai, Shao‐Xing; Li, Hao; Li, Zifan; Xu, Lizhu; Chu, Chu; Qu, Jing; Si, Chenyang; Ji, Weizhi; Liu, Guanghui; Long, Chengzu; Niu, Yuyu

doi:10.1007/s13238-020-00740-8

Cited by 59 publications

(39 citation statements)

References 63 publications

(77 reference statements)

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“…Currently, the CRISPR/Cas9 technology including Base Editor (BE) appears to be the prevalent method for genome editing in general. Indeed, Wang et al succeeded in generating a Hutchinson–Gilford progeria syndrome cynomolgus monkey model using BE 59 . In the present study, we used a different technique – TALEN – because it is highly efficient, and produces less mosaicism 34 .…”

Section: Discussionmentioning

confidence: 99%

A non-human primate model of familial Alzheimer’s disease

Sato¹,

Sasaguri

Kumita

et al. 2020

Preprint

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Alzheimer's disease (AD) is a major cause of dementia, with the number of patients with this condition anticipated to exceed 50 million worldwide in the near future. Despite extensive research efforts, no effective measures are available to facilitate the prevention or treatment of AD, which is due in part to a lack of animal models able to closely replicate a human-like disease state. Here, we describe the generation of three mutant marmoset individuals in which exon 9 of PSEN1 gene product has been deleted (PSEN1-DeltaE9). Such DeltaE9 mutations have been reported to cause early on-set familial AD (references 1-5). We used Transcription Activator-Like Effector Nuclease (TALEN) to destroy the 3' splice site of exon 9 in the marmoset PSEN1 gene. To this end, TALEN exhibits high genome-editing efficacy, generates few off-target effects, and produces minimal mosaicism. Indeed, whole genome sequencing and other analyses illustrated an absence of off-target effects and an apparent absence of mosaicism. Fibroblasts obtained from newborn marmosets exhibited uncleaved full-length presenilin 1 protein (PS1) caused by the perturbation of PS1 endoproteolysis as well as an increased ratio of Abeta42/Abeta40 production, a signature of familial AD pathogenesis. To our knowledge, this is the first non-human primate model of familial AD. We intend to make our marmoset model available to the research community to facilitate the global fight against AD.

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Section: Discussionmentioning

confidence: 99%

A non-human primate model of familial Alzheimer’s disease

Sato¹,

Sasaguri

Kumita

et al. 2020

Preprint

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“…Another observation that is difficult to accommodate in a damage-based conception of ageing is the fact that Hutchinson-Gilford progeria syndrome (HGPS) is caused by a single point mutation in the Lamin A gene (Wang et al, 2020;Eriksson et al, 2003).This observation is difficult to explain in a damage-based conception of ageing, where damage accumulation occurs during lifespan due to changes into balance between damage generation and damage repair, and the consequent accumulation of damage that this implies all along the lifespan of the organism. Could all these complex mechanisms be caused by a point mutation?…”

Section: Experimental Observations In Accordance With the Proposed Modelmentioning

confidence: 99%

The Principle of Continuous Biological Information Flow as the Fundamental Foundation for the Biological Sciences. Implications for Ageing Research

Marsellach¹

2020

Preprint

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The current state of biological knowledge contains an unresolved paradox: life as a continuity in the face of the phenomena of ageing. In this manuscript I propose a theoretical framework that offers a solution for this apparent contradiction. The framework proposed is based on a rethinking of what ageing is at a molecular level, as well as on a rethinking of the mechanisms in charge of the flow of information from one generation to the following ones. I propose an information-based conception of ageing instead of the widely accepted damage-based conception of ageing and propose a full recovery of the chromosome theory of inheritance to describe the intergenerational flow of information. Altogether the proposed framework allows a precise and unique definition of what life is: a continuous flow of biological information. The proposed framework also implies that ageing is merely a consequence of the way in which epigenetically-coded phenotypic characteristics are passed from one generation to the next ones.

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“…This module also collects changes in gene expression profiles during physiological and pathological aging in specific tissues and organs. This includes data such as genome-wide gene expression changes across multiple tissues in the monkey model of the Hutchinson–Gilford progeria syndrome (HGPS) ( 21 ). The RNA-seq module currently contains >18 000 differentially expressed genes (DEGs) that may be related to aging.…”

Section: Database Contentmentioning

confidence: 99%

Aging Atlas: a multi-omics database for aging biology

Liu¹,

Bào²,

Qu³

et al. 2020

Nucleic Acids Research

Self Cite

187

109

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Organismal aging is driven by interconnected molecular changes encompassing internal and extracellular factors. Combinational analysis of high-throughput ‘multi-omics’ datasets (gathering information from genomics, epigenomics, transcriptomics, proteomics, metabolomics and pharmacogenomics), at either populational or single-cell levels, can provide a multi-dimensional, integrated profile of the heterogeneous aging process with unprecedented throughput and detail. These new strategies allow for the exploration of the molecular profile and regulatory status of gene expression during aging, and in turn, facilitate the development of new aging interventions. With a continually growing volume of valuable aging-related data, it is necessary to establish an open and integrated database to support a wide spectrum of aging research. The Aging Atlas database aims to provide a wide range of life science researchers with valuable resources that allow access to a large-scale of gene expression and regulation datasets created by various high-throughput omics technologies. The current implementation includes five modules: transcriptomics (RNA-seq), single-cell transcriptomics (scRNA-seq), epigenomics (ChIP-seq), proteomics (protein–protein interaction), and pharmacogenomics (geroprotective compounds). Aging Atlas provides user-friendly functionalities to explore age-related changes in gene expression, as well as raw data download services. Aging Atlas is freely available at https://bigd.big.ac.cn/aging/index.

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Generation of a Hutchinson–Gilford progeria syndrome monkey model by base editing

Cited by 59 publications

References 63 publications

A non-human primate model of familial Alzheimer’s disease

A non-human primate model of familial Alzheimer’s disease

The Principle of Continuous Biological Information Flow as the Fundamental Foundation for the Biological Sciences. Implications for Ageing Research

Aging Atlas: a multi-omics database for aging biology

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