Supporting data for "Single-cell Transcriptomic Landscape of Nucleated Cells in Umbilical Cord Blood"

Umbilical cord blood (UCB) transplant is a therapeutic option for both pediatric and adult patients with a variety of hematologic diseases such as several types of blood cancers, myeloproliferative disorders, genetic diseases, and metabolic disorders. However, the level of cellular heterogeneity and diversity of nucleated cells in the UCB has not yet been assessed in an unbiased and systemic fashion. In the current study, nucleated cells from UCB were subjected to single-cell RNA sequencing, a technology enabled simultaneous profiling of the gene expression signatures of thousands of cells, generating rich resources for further functional studies. Here, we report the transcriptome of 17,637 UCB cells, covering twelve major cell types. Many of these cell types are comprised of distinct subpopulations. Pseudotemporal ordering of nucleated red blood cells (NRBC) identifies wave-like activation and suppression of transcription regulators, leading to a polarized cellular state, which may reflect NRBC maturation. Progenitor cells in UCB also consist two subpopulations with divergent transcription programs activated, leading to specific cell-fate commitment. Detailed profiling of cytotoxic cell populations unveiled granzymes B and K signatures in NK and NKT cell types in UCB. Collectively, we provide this comprehensive single-cell transcriptomic landscape and show that it can uncover previously unrecognized cell types, pathways and gene expression regulations that may contribute to the efficacy and outcome of UCB transplant, broadening the scope of research and clinical innovations.

脐带血（Umbilical cord blood, UCB）移植是针对患有多种血液系统疾病的儿童与成人患者的治疗选择，这些疾病包括多种血液恶性肿瘤、骨髓增殖性疾病、遗传性疾病及代谢性疾病。然而，目前尚未以无偏倚且系统化的方式评估脐带血中有核细胞的细胞异质性水平与多样性。本研究中，研究人员对脐带血来源的有核细胞开展了单细胞RNA测序（single-cell RNA sequencing）——该技术可同时完成数千个细胞的基因表达特征谱分析，为后续功能研究提供了丰富的资源储备。本研究报道了17637个脐带血细胞的转录组数据，涵盖12种主要细胞类群，其中多数细胞类群还包含独特的亚群结构。对有核红细胞（nucleated red blood cells, NRBC）开展拟时序分析，可观测到转录调控因子呈现波浪式的激活与抑制模式，最终形成极化细胞状态，这一过程或反映有核红细胞的成熟进程。脐带血中的祖细胞同样包含两个亚群，二者激活了迥异的转录程序，进而促成特定的细胞命运定向。对细胞毒性细胞群的精细谱分析揭示，脐带血中的自然杀伤细胞（Natural Killer, NK）与自然杀伤T细胞（Natural Killer T, NKT）呈现颗粒酶B与颗粒酶K的特征性表达谱。综上，本研究构建了全面的单细胞转录组图谱，并证实该图谱可发掘此前未被认知的细胞类群、信号通路及基因表达调控机制，这些发现或有助于提升脐带血移植的疗效与预后，拓宽相关研究与临床创新的边界。