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The breast is a dynamic organ whose response to physiological and pathophysiological conditions alters its disease susceptibility, yet the specific effects of these clinical variables on cell state remain poorly annotated. We present a unified, high-resolution breast atlas by integrating single-cell RNA-seq, mass cytometry, and cyclic immunofluorescence, encompassing a myriad of states. We define cell subtypes within the alveolar, hormone-sensing, and basal epithelial lineages, delineating associations of several subtypes with cancer risk factors, including age, parity, and BRCA2 germline mutation. Of particular interest is a subset of alveolar cells, termed basal-luminal (BL) cells, which exhibits poor transcriptional lineage fidelity, accumulates with age, and carries a gene signature associated with basal-like breast cancer. We further utilize a medium-depletion approach to identify molecular factors regulating cell subtype proportion in organoids. Together, these data are a rich resource to elucidate diverse mammary cell states.

One hundred fifty-seven patients, 126 women and 24 men, 10 to 75 years of age, completed a self-administered questionnaire. The questionnaire contained questions asking about the patients' chief complaint, treatment received before coming to the clinic, the patients' view of their problem, and who informed them of the possible end result of an untreated “TMJ problem.” The results revealed that pain was the most commonly reported complaint (54%), discomfort and headache came second and third (52.2% and 46.5%, respectively). A significant correlation was found between inability to chew and pain, discomfort, tightness in the masticatory muscles, and locking and clicking of the joint. Most patients had received three or more types of treatment before coming to the University of Michigan, TMJ and Oral Facial Pain Clinic. A significant correlation was found between an increased number of reported symptoms and an increase in the number of treatments. The most frequently used treatment methods were pain medication, mouth guard (appliances), and occlusal adjustment. Most patients (84.1%) were referred to the TMJ and Oral Facial Pain Clinic by dentists because of clicking, locking, and limitation of movement, with or without pain.