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 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 that enables 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 12 major cell types. Many of these cell types can be further divided into 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 of 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 uncovers 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.