Cells from umbilical cord blood (UCB), once considered medical waste, are increasingly recognized as valuable therapeutic sources. An advantage of UCB grafts is their ease of accessibility and their high tolerance for HLA mismatches, and a comparatively low risk for graft-vs-host disease (GVHD) (Locatelli et al., 2013). Since the first umbilical cord blood transplant in 1988, UCB has become increasingly important as a graft source for hematopoietic stem cell transplantation (HSCT). Recently, UCB has been increasingly replacing fetal and adult-derived cells in adoptive cell therapy (Berglund et al., 2017).

The number and type of stem cells extracted from UCB are affected by a number of environmental and demographic factors, and it has been shown that these differences are related to disparities in transplant outcomes. Numerous studies have shown that hUCB contains naive and pluripotent stem cells (Jaing et al., 2014), including about 40% of these cells are monocytes (macrophage precursors), 40% are lymphocytes, 10% are neutrophils and other leukocytes, and 10% are stem cells (Stiner et al., 2019). It has been demonstrated that stem cell-based therapies can be used to treat a wide variety of disorders, including liver and severe acute graft-versus-host, autoimmune, neurodegenerative, and other immunerelated diseases (Stiner et al., 2019). In addition, the innate and adaptive immune cells, such as dendritic cells, T lymphocytes, natural killer cells (NKs), and B lymphocytes are modulated by some stem cells in a variety of ways, which lead to inhibit proinflammatory cytokine release reduction and induce peripheral tolerance (Kang et al., 2017).

Gene expression and chromatin accessibility in umbilical cord blood cells is not well understood. The role of genes in determining cell fate plays a crucial role in understanding disease and embryonic development. Gene regulatory networks describe the complex interactions between transcription factors and their target genes. There is mounting evidence linking these gene regulatory networks to disease and development across evolutionary lines. In contrast to previous techniques such as qRT-PCR, which focused on a single gene or set of genes, a complete cellular transcriptome can be analyzed using high-throughput sequencing technology (Weir et al., 2021). However, Due to the large number of cells processed by conventional RNA-seq methods, cellular heterogeneity cannot be addressed, because signals of variable gene expression would be averaged across cells (Hou et al., 2022). To understand biological systems, it is necessary to understand their components. scRNA-seq can be used to address transcriptional heterogeneity, which can elucidate cellular heterogeneity in complex systems and tissues as well as enables the discovery of novel cell types, states, and biomarkers for clinical use (Hou et al., 2021). However, the drivers of gene regulation cannot be directly observed by single cell RNA-seq. As a result, we have limited understanding of how gene regulatory programs are set up and, ultimately, how cell types and states are defined. Several novel multiomic tools have been developed that simultaneously measure gene expression and chromatin accessibility as a means of bridging this gap, enabling direct epigenetic and transcriptomic measurements from the same cell. Chromium Single Cell Multiome ATAC + Gene Expression has been developed by 10x Genomics, which can capture both transcriptomic and epigenomic data in the same single cells, across thousands of cells (Yu et al., 2021). Furthermore, an integrated view of a cell's chromatin landscape and gene expression profile can uncover how cell types and states develop, discover interpret epigenetic profiles and new gene regulatory interactions with key expression markers.

In this study, by integrating scRNA-seq with scATAC-seq technology, we performed unbiased analysis of human UCB cells from 31 to 37 gestational weeks (GW), to gain a better understanding of the regulatory networks and chromatin landscape in UCB cells. As we gain a deeper understanding of stem cell signaling, we may be able to select more specific UCB cell subpopulations or change the expression of UCB cells to provide increased transplantation success.