Single-cell landscape of alternative polyadenylation in human lymphoid hematopoiesis.

IF 5.3 2区 生物学 Q2 CELL BIOLOGY
Jiaqi Qiang, Shan Yu, Jun Li, Yu Rong, Xiaoshuang Wang, Yong Zhu, Fang Wang
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Abstract

Alternative polyadenylation (APA) is an essential post-transcriptional process that produces mature mRNA isoforms by regulating the usage of polyadenylation sites (PASs). APA is involved in lymphocyte activation; however, its role throughout the entire differentiation trajectory remains elusive. Here, we analyzed single-cell 3'-end transcriptome data from healthy subjects to construct a dynamic-APA landscape from hematopoietic stem and progenitor cells (HSPCs) to terminally differentiated lymphocytes. This analysis covered 19973 cells of 12 clusters from five lineages (B cells, CD4+ T cells, CD8+ T cells, natural killer cells, and plasmacytoid dendritic cells). A total of 2364 genes exhibited differential 3'UTR PAS usage, and 3021 genes displayed differential intronic cleavage during lymphoid differentiation. We observed a global trend of 3'UTR shortening during lymphoid differentiation. Nevertheless, specific events of both 3'UTR shortening and lengthening were also identified within each cluster. The APA patterns delineated three differentiation stages: HSPCs, precursor cells, and mature cells. Moreover, we demonstrated that the conversion of naïve T cells to memory T cells was accompanied by dynamic APA in transcription factor-encoding genes (TCF7 and NFATC2IP), immune function-related genes (BCL2, CD5, CD28, GOLT1B, and TMEM59), and protein ubiquitination-related genes (UBE2G1, YPEL5, and SUMO3). These findings expand our understanding of the underlying molecular mechanisms of APA and facilitate studies on the regulatory role of APA in lymphoid hematopoiesis.

人类淋巴造血过程中替代多腺苷酸化的单细胞图谱。
替代多腺苷酸化(APA)是一个重要的转录后过程,它通过调节多腺苷酸化位点(PAS)的使用来产生成熟的 mRNA 异构体。APA 参与了淋巴细胞的活化;然而,它在整个分化过程中的作用仍然难以捉摸。在这里,我们分析了健康人的单细胞3'端转录组数据,构建了从造血干细胞和祖细胞(HSPC)到终末分化淋巴细胞的动态APA图谱。这项分析涵盖了五个系(B 细胞、CD4+ T 细胞、CD8+ T 细胞、自然杀伤细胞和浆细胞树突状细胞)12 个群组的 19973 个细胞。在淋巴细胞分化过程中,共有 2364 个基因显示出不同的 3'UTR PAS 使用情况,3021 个基因显示出不同的内含子裂解情况。我们观察到淋巴细胞分化过程中 3'UTR 缩短的整体趋势。然而,在每个群组中也发现了3'UTR缩短和延长的特定事件。APA 模式划分了三个分化阶段:HSPCs、前体细胞和成熟细胞。此外,我们还证明了幼稚 T 细胞向记忆 T 细胞的转化伴随着转录因子编码基因(TCF7 和 NFATC2IP)、免疫功能相关基因(BCL2、CD5、CD28、GOLT1B 和 TMEM59)和蛋白质泛素化相关基因(UBE2G1、YPEL5 和 SUMO3)的动态 APA。这些发现拓展了我们对 APA 潜在分子机制的理解,有助于研究 APA 在淋巴造血中的调控作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
9.60
自引率
1.80%
发文量
1383
期刊介绍: The Journal of Molecular Cell Biology ( JMCB ) is a full open access, peer-reviewed online journal interested in inter-disciplinary studies at the cross-sections between molecular and cell biology as well as other disciplines of life sciences. The broad scope of JMCB reflects the merging of these life science disciplines such as stem cell research, signaling, genetics, epigenetics, genomics, development, immunology, cancer biology, molecular pathogenesis, neuroscience, and systems biology. The journal will publish primary research papers with findings of unusual significance and broad scientific interest. Review articles, letters and commentary on timely issues are also welcome. JMCB features an outstanding Editorial Board, which will serve as scientific advisors to the journal and provide strategic guidance for the development of the journal. By selecting only the best papers for publication, JMCB will provide a first rate publishing forum for scientists all over the world.
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