Single-cell RNA-sequencing reveals the transcriptional landscape of lacrimal gland in GVHD mouse model

Ocular graft-versus-host disease (oGVHD) is one of the most common complications after allogeneic hematopoietic stem cell transplantation(HSCT). Over 50 % of recipients experienced ocular surface-involved GVHD, mainly as dry-eye disease [1,2]. The veil on the mechanism of oGVHD is still limiting our understanding and subsequent drug development of this disease. oGVDH is recognized as chronic GVHD due to both late-onset and pathological characteristics of chronic inflammation and fibrosis. A proposed conceptual model divided chronic GVHD into three phases: early inflammation caused by tissue injury (phase 1), chronic inflammation, thymic injury, and downregulated B-cell and T-cell immunity (phase 2), and tissue repair with fibrosis (phase 3) [3]. Characters of the ocular surface tissue in the fibrosis stage of oGVHD have been widely investigated. However, little data about the biological events before fibrosis in oGVHD has been revealed.

GVHD is a diverse pathological process involving cellular elements. Not only immune cells such as T cells [4], macrophages [[5], [6], [7]], B cells [8,9], and dendritic cells [10,11], but also a variety of many other cells, including epithelial cells [12,13], fibroblasts [14,15], endothelial cells [16] take part in this process. Therefore, a global investigation of the landscape in oGVHD-involved tissue at the stage before fibrosis formation is necessary to understand better how this process develops. The study focusing on the global landscape of this disease has yet to be reported due to technical limitations. Recently, the development of single-cell RNA-sequencing (scRNA-seq) has made it possible to map the cellular markers and functional states comprehensively, uncover previously unrecognized disease-associated cell populations, and even describe the cell-cell communication networks.

Here, to the best of our knowledge, we first used scRNA-seq to identify lacrimal gland (LG) cell populations involved in oGVHD, characterized their gene expression signatures, and constructed cell-cell communication networks.

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