Publication

Over the past two decades, multiple new methods have been developed for probing the structure and function of human tissues and organ systems. These innovative methods have paved the road toward a new era in medicine, where diseases are subclassified, not only based on histology but also at the molecular level, and often based on an integrated assessment of clinical signs and symptoms, detailed in vivo imaging, and histologic and molecular evaluation of biopsied tissues.

Satiety and hunger are controlled by a complex and distributed neural network. The ‘standard model’ of energy homeostasis as the net product of orexigenic agouti-related protein and anorexigenic pro-opiomelanocortin neurons within the hypothalamus is the cornerstone of our understanding. It is, however, patently incomplete, and fundamental gaps exist in our understanding of the identity and organisation of cell types forming the appetitive neurocircuitry, their functions and the relevance of those identified and characterised in mice to the equivalent human neurocircuitry.

Targeted therapies are being increasingly used in clinical practice and trials. However, tumor heterogeneity among sites of metastatic disease can occur creating a conundrum when utilizing biomarker directed therapies. Here we demonstrate a patient with recurrent uterine carcinosarcoma whose local recurrence and metastatic recurrence had a varied response to paclitaxel in combination with DKN-01, a monoclonal antibody against DKK1, a modulator of Wnt/β-catenin and PI3K/AKT signaling pathways. This may be explained by differences in mutational profile found between the two sites.

The anterior cingulate cortex (ACC) is a critical region of the brain for the emotional and affective components of pain in rodents and humans. Hyperactivity in this region has been observed in neuropathic pain states in both patients and animal models and ablation of this region from cingulotomy, or inhibition with genetics or pharmacology can diminish pain and anxiety.

Senescent cells contribute to pathology and dysfunction in animal models1 [/articles/s43587-021-00142-3#ref-CR1]. Their sparse distribution and heterogenous phenotype have presented challenges to their detection in human tissues. We developed a senescence eigengene approach to identify these rare cells within large, diverse populations of postmortem human brain cells. Eigengenes are useful when no single gene reliably captures a phenotype, like senescence.

PURPOSE: Endometrial cancer (EC) is the most frequently diagnosed gynaecological cancer. The majority of women with EC are treated surgically and have a good outcome, however 25-30% of patients presenting with metastases or recurrent disease do not have effective therapies and have

The emergence of castration resistant prostate cancer is associated with a high mortality and remains an area of unmet clinical need. We recently identified a rare subpopulation of normal prostate progenitor cells, characterized by an intrinsic resistance to androgen-deprivation and marked by the expression of LY6D. We here describe the underlying mechanisms driving castration-resistance of LY6D+ luminal progenitors and their contribution to advanced prostate cancer.

Inner ear development requires the complex interaction of numerous cell types arising from multiple embryologic origins. Current knowledge of inner ear organogenesis is limited primarily to animal models. Although most mechanisms of cellular development show conservation between vertebrate species, there are uniquely human aspects of inner ear development which remain unknown. Our group recently described a model of _in vitro_ human inner ear organogenesis using pluripotent stem cells in a 3D organoid culture system.

Although suppressive myeloid cells have been proposed as a mechanism of resistance to immunotherapy, their role in response to checkpoint inhibitor treatment (CPI) in anti-PD-1 refractory cancers, such as biliary tract cancer (BTC), is largely unknown. We used multiplexed single-cell transcriptomic and epitope sequencing to profile >200,000 peripheral blood mononuclear cells from advanced BTC. In BTC patients, CD14+ monocytes expressing high levels of immunosuppressive cytokines and trafficking molecules involved in chemotaxis (CD14CTX) are associated with resistance to CPI.

Cell types in the human retina are highly heterogeneous with their abundance varying by several orders of magnitude. Here, we generated a multi-omics single-cell atlas of the adult human retina, including over 250K and 150K nuclei for single-nuclei RNA- and ATAC-seq, respectively. This atlas is highly comprehensive, with over 60 distinct cell types identified, achieving a sensitivity of 0.01%.