A genetic disorder reveals a hematopoietic stem cell regulatory network co-opted in leukemia.

The molecular regulation of human hematopoietic stem cell (HSC) maintenance is therapeutically important, but limitations in experimental systems and interspecies variation have constrained our knowledge of this process. Here, we have studied a rare genetic disorder due to MECOM haploinsufficiency, characterized by an early-onset absence of HSCs in vivo. By generating a faithful model of this disorder in primary human HSCs and coupling functional studies with integrative single-cell genomic analyses, we uncover a key transcriptional network involving hundreds of genes that is required for HSC maintenance. Through our analyses, we nominate cooperating transcriptional regulators and identify how MECOM prevents the CTCF-dependent genome reorganization that occurs as HSCs differentiate. We show that this transcriptional network is co-opted in high-risk leukemias, thereby enabling these cancers to acquire stem cell properties. Collectively, we illuminate a regulatory network necessary for HSC self-renewal through the study of a rare experiment of nature.

Ultrasonography of Plantar Fibromatosis: Updated Case Series, Review of the Literature, and a Novel Descriptive Appearance Termed the "Comb Sign".

The purpose of this series is to review the appearance of plantar fibromatosis with high-resolution ultrasonography (US) and highlight a new imaging sign termed the "comb sign." A retrospective study was performed for patients with a clinical diagnosis of plantar fibromatosis. Charts of 43 patients (age range, 26-77 years; mean age, 54 years) were reviewed to gather patient demographics and symptoms. Several US characteristics were evaluated with emphasis on any new imaging features. A total of 57 plantar fibromas in 43 patients were examined. Plantar fibromatosis was seen as a lobular marginated oval nodule along the superficial plantar fascia involving the central or medial cord, often at the middle third (84%) of the plantar fascia, showing posterior acoustic enhancement (65%), mixed echogenicity (82%), and intralesional vascularity (53%). Slightly more than half (51%) of the lesions showed a previously unrecognized appearance, designated the comb sign. This sign was more commonly seen in the setting of larger fibromas (P < .05). Plantar fibromatosis is usually a clinical diagnosis that can be aided by a typical US appearance. Although the imaging characteristics are largely similar to prior literature, this series suggests that most show mixed echogenicity and posterior acoustic enhancement, and approximately half show internal vascularity. A new US sign, termed the comb sign, shows alternating bands of hypoechogenicity and isoechogenicity, particularly in larger plantar fibromas, and can help in further characterization.