Keratin 71 Mutations: From Water Dogs to Woolly Hair

The study of rare genetic disorders of the hair follicle has resulted in the identification of many causative genes, leading to the potential for the development of novel therapeutic approaches for both inherited and acquired hair disorders. In this issue, Fujimoto et al. identify a missense mutation within the keratin 71 (KRT71) gene as the cause for autosomal dominant woolly hair/hypotrichosis in a Japanese family. This represents the first human mutation in KRT71 to be linked to a hair disorder, establishing this gene as an important determinant of mammalian hair texture. Moreover, this finding provides new insight into the relationship between similar phenotypes resulting from mutations in distinct regulatory pathways and underscores the role of the inner root sheath in human hair growth

Pharmacologic inhibition of JAK-STAT signaling promotes hair growth

Several forms of hair loss in humans are characterized by the inability of hair follicles to enter the growth phase (anagen) of the hair cycle after being arrested in the resting phase (telogen). Current pharmacologic therapies have been largely unsuccessful in targeting pathways that can be selectively modulated to induce entry into anagen. We show that topical treatment of mouse and human skin with small-molecule inhibitors of the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway results in rapid onset of anagen and subsequent hair growth. We show that JAK inhibition regulates the activation of key hair follicle populations such as the hair germ and improves the inductivity of cultured human dermal papilla cells by controlling a molecular signature enriched in intact, fully inductive dermal papillae. Our findings open new avenues for exploration of JAK-STAT inhibition for promotion of hair growth and highlight the role of this pathway in regulating the activation of hair follicle stem cells

Social search and discovery using a unified approach

This research explores new ways to augment the search and discovery of relations between Web 2.0 entities using multi-ple types and sources of social information. Our goal is to allow the search for all object types such as documents, per-sons and tags, while retrieving related objects of all types. We implemented a social-search engine using a unified ap-proach, where the search space is expanded to represent het-erogeneous information objects that are interrelated by sev-eral relation types. Our solution is based on multifaceted search, which provides an efficient update mechanism for relations between objects, as well as efficient search over the heterogeneous data. We describe a social search engine po-sitioned within a large enterprise, applied over social data gathered from several Web 2.0 applications. We conducted a large user study with over 600 people to evaluate the con-tribution of social data for search. Our results demonstrate the high precision of social search results and confirm the strong relationship of users and tags to the topics retrieved

Zfx controls the self-renewal of embryonic and hematopoietic stem cells

Stem cells (SC) exhibit a unique capacity for self-renewal in an undifferentiated state. It is unclear whether the self-renewal of pluripotent embryonic SC (ESC) and of tissue-specific adult SC such as hematopoietic SC (HSC) is controlled by common mechanisms. The deletion of transcription factor Zfx impaired the self-renewal but not the differentiation capacity of murine ESC; conversely, Zfx overexpression facilitated ESC self-renewal by opposing differentiation. Furthermore, Zfx deletion abolished the maintenance of adult HSC but did not affect erythromyeloid progenitors or fetal HSC. Zfx-deficient ESC and HSC showed increased apoptosis and SC-specific upregulation of stress-inducible genes. Zfx directly activated common target genes in ESC and HSC, as well as ESC-specific target genes including ESC self-renewal regulators Tbx3 and Tcl1. These studies identify Zfx as a shared transcriptional regulator of ESC and HSC, suggesting a common genetic basis of self-renewal in embryonic and adult SC