Publications

Cellular identity in complex multicellular organisms is determined in part by the physical organization of cells. However, large-scale investigation of the cellular interactome remains technically challenging. Here we develop cell interaction by multiplet sequencing (CIM-seq), an unsupervised and high-throughput method to analyze direct physical cell-cell interactions between cell types present in a tissue. CIM-seq is based on RNA sequencing of incompletely dissociated cells, followed by computational deconvolution into constituent cell types.

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) enzymes are secreted metalloproteinases with major roles in development, morphogenesis, and tissue repair via the assembly and degradation of extracellular matrix (ECM). In this study, we investigated the role of ADAMTS18 in the development of the reproductive tract in female mice by phenotyping Adamts18 knockout (Adamts18-/-) mice. The results showed that Adamst18 mRNAs were abundantly expressed in vaginal epithelial cells and muscularis cells of the developing vagina.

To investigate programmed cell death ligand 1 (PD-L1) expression patterns and define the associations among PD-L1, molecular subtypes, pathological features, and survival in a cohort of 833 patients with endometrial cancer, of whom approximately half had high-risk disease.Using direct sequencing of the polymerase epsilon (POLE) exonuclease domain as well as immunohistochemistry for mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6) and p53, we stratified endometrial cancers into four molecular subtypes: POLE ultramutated, MMR-deficient, p53-mutant, and non-specific molecular profil

Mechanical stimuli including loading after birth promote bone growth. However, little is known about how mechanical force triggers biochemical signals to regulate bone growth. Here, we identified a periosteal-osteoblast-derived secretory peptide, Osteocrin (OSTN), as a mechanotransducer involved in load-induced long bone growth. OSTN produced by periosteal osteoblasts regulates growth plate growth by enhancing C-type natriuretic peptide (CNP)-dependent proliferation and maturation of chondrocytes, leading to elongation of long bones.

Proper lung function relies on the precise balance of specialized epithelial cells that coordinate to maintain homeostasis. Herein, we describe essential roles for the transcriptional regulators YAP/TAZ in maintaining lung epithelial homeostasis, reporting that conditional deletion of Yap and Wwtr1/Taz in the lung epithelium of adult mice results in severe defects, including alveolar disorganization and the development of airway mucin hypersecretion.

The mediobasal hypothalamus (MBH; arcuate nucleus of the hypothalamus [ARH] and median eminence [ME]) is a key nutrient sensing site for the production of the complex homeostatic feedback responses required for the maintenance of energy balance. Here, we show that refeeding after an overnight fast rapidly triggers proliferation and differentiation of oligodendrocyte progenitors, leading to the production of new oligodendrocytes in the ME specifically.

The utricle is a vestibular sensory organ that requires mechanosensitive hair cells to detect linear acceleration. In neonatal mice, new hair cells are derived from non-sensory supporting cells, yet cell type diversity and mechanisms of cell addition remain poorly characterized. Here, we perform computational analyses on single-cell transcriptomes to categorize cell types and resolve 14 individual sensory and non-sensory subtypes. Along the periphery of the sensory epithelium, we uncover distinct groups of transitional epithelial cells, marked by Islr, Cnmd, and Enpep expression.

The endocannabinoids have been shown to target the afferents of hypothalamic neurons via cannabinoid 1 receptor (CB1) and thereby to influence their excitability at various physiological and/or pathological processes. Kisspeptin (KP) neurons form afferents of multiple neuroendocrine cells and influence their activity via signaling through a variation of co-expressed classical neurotransmitters and neuropeptides.

Effective control of ipomoviruses that cause cassava brown streak disease (CBSD) in Africa has remained problematic despite eight remarkable decades (1930-2021) of research efforts. Molecular mechanisms underlying resistance breakdown in genetically improved cassava are still unknown. The vast genetic diversity of cassava brown streak viruses, which is crucial for the improvement of routine reverse transcription polymerase chain reaction (RT-qPCR) assays in CBSD-endemic regions of Africa, is controversial and underrepresented.

Intestinal mucosal healing is the primary therapeutic goal of medical treatments for inflammatory bowel disease (IBD). Epithelial stem cells are key players in the healing process. Lgr5+ stem cells maintain cellular turnover during homeostasis in the colonic crypt. However, they are lost and dispensable for repair in a wide variety of injury models, including dextran sulfate sodium (DSS) colitis, radiation, helminth infection, and T-cell activation. The direct loss of Lgr5+ cells activates a plasticity response in the epithelium in which other cell types can serve as stem cells.