Single-cell gene and isoform expression analysis reveals signatures of ageing in haematopoietic stem and progenitor cells.
Single-cell gene and isoform expression analysis reveals signatures of ageing in haematopoietic stem and progenitor cells.
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单细胞基因和异构体表达分析揭示了造血干细胞和祖细胞衰老的特征。
DOI：
10.1038/s42003-023-04936-6
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发表时间：
2023-05-24
影响因子：
5.9
通讯作者：
Macaulay, Iain C.
中科院分区：
文献类型：
--
作者：
Mincarelli, Laura;Uzun, Vladimir;Wright, David;Scoones, Anita;Rushworth, Stuart A.;Haerty, Wilfried;Macaulay, Iain C.
单细胞方法揭示了造血层次是一个连续的分化，从干细胞到定向祖细胞，以基因表达的变化为标志。然而，这些方法中的许多忽略了异构体水平的信息，因此不能捕获系统内的可变剪接的程度。在这里，我们提出了一个集成的短和长读单细胞RNA-seq分析造血干细胞和祖细胞。我们证明，在标准的短读单细胞分析中检测到的基因中，有一半以上表达为多种，通常功能不同的同种型，包括许多转录因子和关键细胞因子受体。我们观察到全球和HSC特异性的基因表达与衰老的变化，但有限的影响，对异构体的使用老化。因此，在造血中整合单细胞和细胞类型特异性同种型景观为异质组织的全面分子分析提供了新的参考，以及对转录复杂性，细胞类型特异性剪接事件和衰老后果的新见解。使用长读序的单细胞转录组学在造血干细胞和祖细胞中实现了基因和同种型表达，为理解细胞分化中的选择性剪接提供了新的见解。
Single-cell approaches have revealed that the haematopoietic hierarchy is a continuum of differentiation, from stem cell to committed progenitor, marked by changes in gene expression. However, many of these approaches neglect isoform-level information and thus do not capture the extent of alternative splicing within the system. Here, we present an integrated short- and long-read single-cell RNA-seq analysis of haematopoietic stem and progenitor cells. We demonstrate that over half of genes detected in standard short-read single-cell analyses are expressed as multiple, often functionally distinct, isoforms, including many transcription factors and key cytokine receptors. We observe global and HSC-specific changes in gene expression with ageing but limited impact of ageing on isoform usage. Integrating single-cell and cell-type-specific isoform landscape in haematopoiesis thus provides a new reference for comprehensive molecular profiling of heterogeneous tissues, as well as novel insights into transcriptional complexity, cell-type-specific splicing events and consequences of ageing. Single-cell transcriptomics using long-read sequencing achieves both gene and isoform expression in haematopoietic stem and progenitor cells, providing novel insights into the understanding of alternative splicing in cellular differentiation.
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影响因子：
14.9
作者：
Frankish A;Diekhans M;Ferreira AM;Johnson R;Jungreis I;Loveland J;Mudge JM;Sisu C;Wright J;Armstrong J;Barnes I;Berry A;Bignell A;Carbonell Sala S;Chrast J;Cunningham F;Di Domenico T;Donaldson S;Fiddes IT;García Girón C;Gonzalez JM;Grego T;Hardy M;Hourlier T;Hunt T;Izuogu OG;Lagarde J;Martin FJ;Martínez L;Mohanan S;Muir P;Navarro FCP;Parker A;Pei B;Pozo F;Ruffier M;Schmitt BM;Stapleton E;Suner MM;Sycheva I;Uszczynska-Ratajczak B;Xu J;Yates A;Zerbino D;Zhang Y;Aken B;Choudhary JS;Gerstein M;Guigó R;Hubbard TJP;Kellis M;Paten B;Reymond A;Tress ML;Flicek P
通讯作者：
Flicek P
DOI：
10.1126/science.1251033
发表时间：
2014-09-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chen L;Kostadima M;Martens JHA;Canu G;Garcia SP;Turro E;Downes K;Macaulay IC;Bielczyk-Maczynska E;Coe S;Farrow S;Poudel P;Burden F;Jansen SBG;Astle WJ;Attwood A;Bariana T;de Bono B;Breschi A;Chambers JC;Consortium B;Choudry FA;Clarke L;Coupland P;van der Ent M;Erber WN;Jansen JH;Favier R;Fenech ME;Foad N;Freson K;van Geet C;Gomez K;Guigo R;Hampshire D;Kelly AM;Kerstens HHD;Kooner JS;Laffan M;Lentaigne C;Labalette C;Martin T;Meacham S;Mumford A;Nürnberg S;Palumbo E;van der Reijden BA;Richardson D;Sammut SJ;Slodkowicz G;Tamuri AU;Vasquez L;Voss K;Watt S;Westbury S;Flicek P;Loos R;Goldman N;Bertone P;Read RJ;Richardson S;Cvejic A;Soranzo N;Ouwehand WH;Stunnenberg HG;Frontini M;Rendon A
通讯作者：
Rendon A
影响因子：
7.8
作者：
Adusumalli, Swarnaseetha;Ngian, Zhen-Kai;Ong, Chin-Tong
通讯作者：
Ong, Chin-Tong
影响因子：
23.9
作者：
Dykstra, Brad;Kent, David;Eaves, Connie
通讯作者：
Eaves, Connie
影响因子：
10.1
作者：
Carlos Montero, Juan;Lopez-Perez, Ricardo;Pandiella, Atanasio
通讯作者：
Pandiella, Atanasio