Taibo Li

Morphogenesis of the anterior segment (AS) is crucial for healthy ocular physiology and vision, but is only partially understood. The Schlemm’s canal (SC) and trabecular meshwork (TM) are essential drainage tissues within the AS, and their proper development and function are critical for maintaining normal intraocular pressure; abnormalities in either tissue can result in elevated pressure and glaucoma. Here, we use single-cell transcriptomic profiling to provide high-resolution molecular detail of mouse AS development with a particular focus on SC and TM. We report transcriptomes for ~130,000 single cells at key developmental stages from postnatal day 2 (P2) to P60. We provide the first annotation of cell types across these developmental stages and crucial information about dynamic changes in pathways/gene expression. Further, we trace developmental trajectories for TM cell and SC endothelial cell (SEC) subtypes and determine genes and signaling networks driving their specific cell fates. We demonstrate dynamic changes in signaling interactions between SC and the TM cells during their synchronized development. Collectively, our data lay a deep molecular foundation for AS development that will direct understanding of normal ocular physiology, glaucoma, and other AS conditions.

Objectives: Active proliferative LN is associated with elevated urinary neutrophil granule proteins such as PR3, implicating active cellular degranulation in LN. Yet, mature neutrophils are rarely observed in LN biopsies, raising the possibility of an unrecognized cellular source. We aimed to identify and characterize PR3-expressing myeloid cells in LN kidneys using a spatially resolved multi-omics approach. Methods: Serial immunohistochemistry (10-plex) and spatial transcriptomics were employed to assess the distribution of PR3+ cells across renal tissue and characterize their cellular phenotype. Results: PR3+ cells were abundant in LN kidney biopsies, but with marked inter-patient heterogeneity. These cells were predominantly localized to the tubulointerstitium and showed similar distribution in both proliferative and membranous LN. In contrast, intraglomerular PR3+ cells were enriched in proliferative LN and correlated with the NIH activity index. Phenotype analysis identified four subsets of PR3+ cells, consistent with a monocyte/neutrophil lineage. Most PR3+ cells lacked multilobate nuclei, distinguishing them from mature neutrophils, suggesting that these cells may be overlooked by conventional light microscopy. Conclusions: PR3+ myeloid cells are a prominent and heterogeneous population in LN. While intraglomerular PR3+ cells were specific to proliferative LN and correlated with histologic activity, the widespread presence of PR3+ cells in the tubulointerstitium suggests broader involvement in renal inflammation than previously recognized. These findings reveal a potentially overlooked immune cell population that may contribute to renal injury in LN.

Morphogenesis of the anterior segment (AS) is crucial for healthy ocular physiology and vision but is only partially understood. The Schlemm’s canal (SC) and trabecular meshwork (TM) are essential drainage tissues within the AS, and their proper development and function are critical for maintaining normal intraocular pressure; abnormalities in either tissue can result in elevated pressure and glaucoma. Here, we use single-cell transcriptomic profiling to provide high-resolution molecular detail of AS development with a particular focus on SC and TM. We report transcriptomes for ∼130,000 single cells at key developmental stages from postnatal day 2 (P2) to P60. We provide the first annotation of cell types across these developmental stages and crucial information about dynamic changes in pathways/gene expression. Further, we trace developmental trajectories for TM cell and SC endothelial cell (SEC) subtypes and determine genes and signaling networks driving their specific cell fates. We demonstrate dynamic changes in signaling interactions between SC and the TM cells during their synchronized development. Collectively, our data lay a deep molecular foundation for AS development that will direct understanding of normal ocular physiology, glaucoma, and other AS conditions.

Immunohistochemical staining of CRPC-SCL models

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AR-low prostate cancer models exhibit loss of AP-1/YAP TAZ binding and a decrease in AR gene expression upon KMT2D knockdown

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Top enriched pathways upon DHT treatment, PI3K inhibition and the combination with KMT2D knockdown in LNCaP AR-high cells

Top enriched pathways upon DHT treatment and PI3K inhibition in LNCaP AR-high cells

AR-low prostate cancer models display loss of AP-1/YAP TAZ binding profiles and downregulation of AR gene expression profiles with KMT2D knockdown