Single-Cell RNA-Sequencing Reveals a Continuous Spectrum of Differentiation in Hematopoietic Cells.
Single-Cell RNA-Sequencing Reveals a Continuous Spectrum of Differentiation in Hematopoietic Cells.
复制标题
DOI：
10.1016/j.celrep.2015.12.082
复制
发表时间：
2016-02-02
期刊：
影响因子：
8.8
通讯作者：
Cvejic A
中科院分区：
文献类型：
--
作者：
Macaulay IC;Svensson V;Labalette C;Ferreira L;Hamey F;Voet T;Teichmann SA;Cvejic A
控制造血的转录程序主要通过造血干细胞和祖细胞的群体水平分析进行研究，但不能揭示分化过程的连续性质。在这里，我们将单细胞 RNA 测序应用于斑马鱼的造血细胞群，因为它们正在进行血小板谱系定型。通过计算重建它们的发育年表，我们能够将每个细胞沿着从干细胞到成熟细胞的连续体放置，从而完善传统的谱系树。细胞沿着这个连续体的进展以高度协调的转录程序为特征，随着谱系特异性基因表达的增加，参与细胞增殖和核糖体生物合成的基因同时受到抑制。在该程序中，关键谱系调节因子的表达存在很大的异质性。总体而言，随着细胞进行谱系定型，表达的基因总数以及细胞的总 mRNA 含量都会减少。单细胞 RNA 测序揭示了血小板发育的连续性 协调的转录程序控制着分化的进程 分化过程中表达的基因数量和每个细胞的 mRNA 含量减少 斑马鱼血小板在循环中保持转录活性 根据 scRNA-seq 数据对血小板发育年表进行计算重建，揭示了分化过程的连续性。麦考利等人。表明高度协调的转录程序表征了细胞沿着这个连续体的进展。在该程序中，关键谱系调节因子的表达存在很大的异质性。
The transcriptional programs that govern hematopoiesis have been investigated primarily by population-level analysis of hematopoietic stem and progenitor cells, which cannot reveal the continuous nature of the differentiation process. Here we applied single-cell RNA-sequencing to a population of hematopoietic cells in zebrafish as they undergo thrombocyte lineage commitment. By reconstructing their developmental chronology computationally, we were able to place each cell along a continuum from stem cell to mature cell, refining the traditional lineage tree. The progression of cells along this continuum is characterized by a highly coordinated transcriptional program, displaying simultaneous suppression of genes involved in cell proliferation and ribosomal biogenesis as the expression of lineage specific genes increases. Within this program, there is substantial heterogeneity in the expression of the key lineage regulators. Overall, the total number of genes expressed, as well as the total mRNA content of the cell, decreases as the cells undergo lineage commitment. Single-cell RNA-sequencing reveals the continuous nature of thrombocyte development Coordinated transcriptional programs govern progression of differentiation Number of genes expressed and mRNA content per cell decrease during differentiation Zebrafish thrombocytes remain transcriptionally active in circulation Computational reconstruction of the thrombocyte’s developmental chronology from scRNA-seq data reveals the continuous nature of the differentiation process. Macaulay et al. show that a highly coordinated transcriptional program characterizes the progression of cells along this continuum. Within this program, there is substantial heterogeneity in the expression of key lineage regulators.