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高分辨率长读端粒测序揭示衰老和癌症中的动态机制。

High resolution long-read telomere sequencing reveals dynamic mechanisms in aging and cancer.

机构信息

Salk Institute for Biological Studies, La Jolla, CA, 92037, USA.

Oxford Nanopore Technologies, Inc., New York, NY, USA.

出版信息

Nat Commun. 2024 Jun 18;15(1):5149. doi: 10.1038/s41467-024-48917-7.

Abstract

Telomeres are the protective nucleoprotein structures at the end of linear eukaryotic chromosomes. Telomeres' repetitive nature and length have traditionally challenged the precise assessment of the composition and length of individual human telomeres. Here, we present Telo-seq to resolve bulk, chromosome arm-specific and allele-specific human telomere lengths using Oxford Nanopore Technologies' native long-read sequencing. Telo-seq resolves telomere shortening in five population doubling increments and reveals intrasample, chromosome arm-specific, allele-specific telomere length heterogeneity. Telo-seq can reliably discriminate between telomerase- and ALT-positive cancer cell lines. Thus, Telo-seq is a tool to study telomere biology during development, aging, and cancer at unprecedented resolution.

摘要

端粒是线性真核染色体末端的保护性核蛋白结构。端粒的重复性质和长度一直以来都对个体人类端粒的组成和长度的精确评估构成挑战。在这里,我们提出了 Telo-seq 方法,该方法使用 Oxford Nanopore Technologies 的天然长读测序来解析批量、染色体臂特异性和等位基因特异性的人类端粒长度。Telo-seq 可以在五个倍增倍数内解析端粒缩短,并揭示样本内、染色体臂特异性、等位基因特异性的端粒长度异质性。Telo-seq 可以可靠地区分端粒酶和 ALT 阳性癌细胞系。因此,Telo-seq 是一种在前所未有的分辨率下研究发育、衰老和癌症中端粒生物学的工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61e3/11189484/80683b57d4c5/41467_2024_48917_Fig1_HTML.jpg

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