Differential chromatin accessibility accompanies and mediates transcriptional control of diverse cell fates and their differentiation during embryogenesis. While the critical role of NKX2-1 and its transcriptional targets in lung morphogenesis and pulmonary epithelial cell differentiation is increasingly known, mechanisms by which chromatin accessibility alters the epigenetic landscape and how NKX2-1 interacts with other co-activators required for alveolar epithelial cell differentiation and function are not well understood. Here, we demonstrate that the paired domain zinc finger transcriptional regulators PRDM3 and PRDM16 regulate chromatin accessibility to mediate cell differentiation decisions during lung morphogenesis. Combined deletion of
Abstract Lung epithelial progenitors use a complex network of known and predicted transcriptional regulators to influence early lung development. Here, we evaluate the function of one predicted regulator, Cux1, that we identified from transcriptional regulatory analysis of the SOX9 + distal lung progenitor network. We generated a new Cux1-floxed mouse model and created an epithelial-specific knockout of Cux1 using Shh-Cre (Cux1 ShhCre-LOF ). Postnatal Cux1 ShhCre-LOF animals recapitulate key skin phenotypic features found in prior constitutive Cux1 knockout animals, confirming functionality of the new floxed model. Postnatal Cux1 ShhCre-LOF mice displayed subtle alveolar simplification and a transient delay in alveologenesis without persistent lung phenotypes or alterations in lung epithelial cell allocation. Cux1 ShhCre-LOF mice developed failure to thrive in their second and third weeks of life due to delayed ileal maturation, which similarly resolves by postnatal day 35. Finally, we challenged Cux1 ShhCre-LOF with influenza-mediated lung injury to demonstrate that Cux1 ShhCre-LOF mice undergo productive alveolar regeneration that is indistinguishable from WT animals. Together, these findings indicate that epithelial-specific loss of Cux1 leads to transient developmental delays in the skin, lung, and intestine without defects in definitive organogenesis. One-Sentence Summary Deletion of key DNA binding domains leads to loss of Cux1 function in the lung, intestine, and skin characterized by transient failure to thrive without significant adult disease.
Introduction: Iododerma is a rare, delayed type IV hypersensitivity reaction due to iodine deposition within the skin. With only a few published case reports, iododerma as a syndrome has been associated with exposure to iodine-containing materials such as contrast media, amiodarone, or povidone-iodine solution, with most cases involving lesions along the face and upper extremities (1). Diagnosis of iododerma is difficult, as lesions can raise concern for infection or vasculitis. We highlight a case of iododerma leading to airway compromise which was successfully treated with hemodialysis. Description: A 51 yo F with a PMH of diabetes mellitus, CKD stage IV, and diastolic heart failure presented with symptomatic anemia and underwent workup that included a CT abdomen and pelvis with oral contrast. She returned nine days later with evolving necrotic skin lesions within the perioral and periorbital areas. She developed facial and supraglottic mucosal edema with extensively sloughing bullous lesions and required intubation. A skin biopsy demonstrated neutrophilic infiltrates with a cryptococcoid appearance consistent with neutrophilic dermatosis. Urine and serum iodine were significantly elevated (15143.4 and 10822.5 respectively), consistent with a diagnosis of iododerma. She was started on high dose corticosteroids and initiated on intermittent hemodialysis to assist with clearance of iodine. Following three sessions of hemodialysis, patient had a significant clinical improvement and reduction in iodine levels with successful extubation on hospital day 11. Discussion: Iododerma is largely a diagnosis of exclusion but should be considered in patients with suggestive skin lesions and recent exposure to iodine-containing materials, particularly patients with underlying renal dysfunction. Diagnosis is typically made with a skin biopsy demonstrating neutrophilic infiltrates with structures that mimic Cryptococcus, in conjunction with elevated serum and urine iodine levels (2). While treatment with steroids is typical, we highlight a case where hemodialysis led to rapid clinical improvement in a very severe case of iododerma, suggesting utility in the ICU setting. 1. Tasker et al., 2019. Clin Exp Dermatol, 44: 844-860. 2. Runge et al, 2020. JAAD Case Reports, 6 (4): 319-322.
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