德国欧洲分子生物学实验室Jan O. Korbel等研究人员合作揭示造血干细胞和祖细胞中马赛克结构变异的细胞类型特异性后果。相关论文发表在2024年5月28日出版的《自然—遗传学》杂志上。

据介绍，人们对正常组织中mSV的功能影响和细胞背景研究不足。

附：英文原文

Title: Cell-type-specific consequences of mosaic structural variants in hematopoietic stem and progenitor cells

Author: Grimes, Karen, Jeong, Hyobin, Amoah, Amanda, Xu, Nuo, Niemann, Julian, Raeder, Benjamin, Hasenfeld, Patrick, Stober, Catherine, Rausch, Tobias, Benito, Eva, Jann, Johann-Christoph, Nowak, Daniel, Emini, Ramiz, Hoenicka, Markus, Liebold, Andreas, Ho, Anthony, Shuai, Shimin, Geiger, Hartmut, Sanders, Ashley D., Korbel, Jan O.

Issue&Volume: 2024-05-28

Abstract: The functional impact and cellular context of mosaic structural variants (mSVs) in normal tissues is understudied. Utilizing Strand-seq, we sequenced 1,133 single-cell genomes from 19 human donors of increasing age, and discovered the heterogeneous mSV landscapes of hematopoietic stem and progenitor cells. While mSVs are continuously acquired throughout life, expanded subclones in our cohort are confined to individuals >60. Cells already harboring mSVs are more likely to acquire additional somatic structural variants, including megabase-scale segmental aneuploidies. Capitalizing on comprehensive single-cell micrococcal nuclease digestion with sequencing reference data, we conducted high-resolution cell-typing for eight hematopoietic stem and progenitor cells. Clonally expanded mSVs disrupt normal cellular function by dysregulating diverse cellular pathways, and enriching for myeloid progenitors. Our findings underscore the contribution of mSVs to the cellular and molecular phenotypes associated with the aging hematopoietic system, and establish a foundation for deciphering the molecular links between mSVs, aging and disease susceptibility in normal tissues.

DOI: 10.1038/s41588-024-01754-2

Source: https://www.nature.com/articles/s41588-024-01754-2