Long noncoding RNAs of single hematopoietic stem and progenitor cells in healthy and dysplastic human bone marrow
Long noncoding RNAs of single hematopoietic stem and progenitor cells in healthy and dysplastic human bone marrow
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DOI：
10.3324/haematol.2018.208926
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发表时间：
2019-04-30
期刊：
影响因子：
10.1
通讯作者：
Young, Neal S.
中科院分区：
文献类型：
--
作者：
Wu, Zhijie;Gao, Shouguo;Young, Neal S.
长链非编码RNA（lncRNA）是细胞分化和发育的调节因子。人类造血干细胞和祖细胞中的lncRNA转录组尚未全面定义。我们通过单细胞RNA测序和从头转录组重建研究了979个人骨髓来源的CD34（+）细胞中的lncRNA。我们总共鉴定了3，173个lncRNA，其中2，365个是以前未知的，我们表征了lncRNA的茎，分化和成熟特征。lncRNA表达表现出高细胞间变异，这仅在单细胞分析中明显。lncRNA表达遵循谱系特异性和高度动态模式在早期造血。造血细胞中的lncRNA与已知功能的蛋白质编码基因在造血和细胞命运决定中密切相关，并且lncRNA在造血中的潜在调节作用是通过蛋白质编码基因的投射来估算的。我们的特点lncRNA优先表达在造血干细胞和各种下游分化谱系祖细胞。我们还分析了骨髓增生异常综合征患者的单细胞，特别是非整倍体细胞中的lncRNA表达。我们的研究提供了人类造血干细胞和祖细胞中lncRNA的全局视图。我们观察到一个高度有序的模式lncRNA的表达和参与调节早期造血，并协调异常信使RNA和lncRNA转录组发育不良的造血。
Long noncoding RNAs (lncRNAs) are regulators of cell differentiation and development. The lncRNA transcriptome in human hematopoietic stem and progenitor cells is not comprehensively defined. We investigated lncRNAs in 979 human bone marrow-derived CD34(+) cells by single cell RNA sequencing followed by de novo transcriptome reconstruction. We identified 3,173 lncRNAs in total, among which 2,365 were previously unknown, and we characterized lncRNA stem, differentiation, and maturation signatures. lncRNA expression exhibited high cell-to-cell variation, which was only apparent in single cell analysis. lncRNA expression followed a lineage-specific and highly dynamic pattern during early hematopoiesis. lncRNAs in hematopoietic cells closely correlated with protein-coding genes of known functions in the regulation of hematopoiesis and cell fate decisions, and the potential regulatory roles of lncRNAs in hematopoiesis were imputed by projection from protein-coding genes with a "guilt-by-association" approach. We characterized lncRNAs preferentially expressed in hematopoietic stem cells and in various downstream differentiated lineage progenitors. We also profiled lncRNA expression in single cells from patients with myelodysplastic syndromes and in aneuploid cells in particular. Our study provides a global view of lncRNAs in human hematopoietic stem and progenitor cells. We observed a highly ordered pattern of lncRNA expression and participation in regulation of early hematopoiesis, and coordinate aberrant messenger RNA and lncRNA transcriptomes in dysplastic hematopoiesis.