School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China.
BGI-Shenzhen, Shenzhen 518083, China.
Gigascience. 2019 May 1;8(5). doi: 10.1093/gigascience/giz047.
For both pediatric and adult patients, umbilical cord blood (UCB) transplant is a therapeutic option for a variety of hematologic diseases, such as blood cancers, myeloproliferative disorders, genetic diseases, and metabolic disorders. However, the level of cellular heterogeneity and diversity of nucleated cells in UCB has not yet been assessed in an unbiased and systemic fashion. In the present study, nucleated cells from UCB were subjected to single-cell RNA sequencing to simultaneously profile the gene expression signatures of thousands of cells, generating a rich resource for further functional studies. Here, we report the transcriptomes of 17,637 UCB cells, covering 12 major cell types, many of which can be further divided into distinct subpopulations.
Pseudotemporal ordering of nucleated red blood cells identifies wave-like activation and suppression of transcription regulators, leading to a polarized cellular state, which may reflect nucleated red blood cell maturation. Progenitor cells in UCB also comprise 2 subpopulations with activation of divergent transcription programs, leading to specific cell fate commitment. Detailed profiling of cytotoxic cell populations unveiled granzymes B and K signatures in natural killer and natural killer T-cell types in UCB.
Taken together, our data form a comprehensive single-cell transcriptomic landscape that reveals previously unrecognized cell types, pathways, and mechanisms of gene expression regulation. These data may contribute to the efficacy and outcome of UCB transplant, broadening the scope of research and clinical innovations.
对于儿科和成人患者,脐带血(UCB)移植是治疗各种血液疾病的一种治疗选择,例如血液癌、骨髓增生性疾病、遗传疾病和代谢疾病。然而,UCB 中核细胞的细胞异质性和多样性水平尚未以无偏倚和系统的方式进行评估。在本研究中,UCB 中的核细胞进行了单细胞 RNA 测序,以同时对数千个细胞的基因表达特征进行分析,为进一步的功能研究提供了丰富的资源。在这里,我们报告了 17637 个 UCB 细胞的转录组,涵盖了 12 种主要细胞类型,其中许多细胞类型可以进一步分为不同的亚群。
有核红细胞的拟时序排序确定了转录因子的波状激活和抑制,导致细胞极化状态,这可能反映了有核红细胞的成熟。UCB 中的祖细胞也包含 2 个亚群,它们激活了不同的转录程序,导致特定的细胞命运决定。细胞毒性细胞群的详细分析揭示了 UCB 中自然杀伤细胞和自然杀伤 T 细胞类型中的 granzyme B 和 K 特征。
总之,我们的数据形成了一个全面的单细胞转录组景观,揭示了以前未被识别的细胞类型、途径和基因表达调控机制。这些数据可能有助于 UCB 移植的疗效和结果,拓宽了研究和临床创新的范围。