德國(guó)歐洲分子生物學(xué)實(shí)驗(yàn)室Jan O. Korbel等研究人員合作揭示造血干細(xì)胞和祖細(xì)胞中馬賽克結(jié)構(gòu)變異的細(xì)胞類型特異性后果。相關(guān)論文發(fā)表在2024年5月28日出版的《自然—遺傳學(xué)》雜志上。
利用Strand-seq技術(shù)，研究人員對(duì)19名年齡不斷增長(zhǎng)的人類捐獻(xiàn)者的1133個(gè)單細(xì)胞基因組進(jìn)行了測(cè)序，發(fā)現(xiàn)了造血干細(xì)胞和祖細(xì)胞中異質(zhì)性的馬賽克結(jié)構(gòu)變體（mSV）景觀。雖然mSV在人的一生中會(huì)不斷獲得，但在研究人員的隊(duì)列中，擴(kuò)增的亞克隆僅限于年齡大于60歲的個(gè)體。已經(jīng)攜帶mSV的細(xì)胞更有可能獲得額外的體細(xì)胞結(jié)構(gòu)變異，包括兆堿基規(guī)模的節(jié)段非整倍體。
利用全面的單細(xì)胞微球蛋白核酸酶消化和測(cè)序參考數(shù)據(jù)，研究人員對(duì)八個(gè)造血干細(xì)胞和祖細(xì)胞進(jìn)行了高分辨率細(xì)胞分型?？寺U(kuò)增的mSV通過(guò)失調(diào)多種細(xì)胞通路和富集髓系祖細(xì)胞，破壞了正常的細(xì)胞功能。這些發(fā)現(xiàn)強(qiáng)調(diào)了mSV對(duì)與造血系統(tǒng)衰老相關(guān)的細(xì)胞和分子表型的貢獻(xiàn)，并為破譯正常組織中mSV、衰老和疾病易感性之間的分子聯(lián)系奠定了基礎(chǔ)。
據(jù)介紹，人們對(duì)正常組織中mSV的功能影響和細(xì)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.
來(lái)源：科學(xué)網(wǎng)
原標(biāo)題：研究揭示造血干細(xì)胞和祖細(xì)胞中馬賽克結(jié)構(gòu)變異的細(xì)胞類型特異性后果
作者：小柯機(jī)器人