Expression of RNA-Binding Protein Musashi in Hair Follicle Development and Hair Cycle Progression

Abstract

Epithelial stem cells reside in the hair follicle (HF) bulge region and possess the ability to differentiate into a variety of cutaneous epithelial cells. The evolutionarily conserved Musashi family of RNA-binding proteins is associated with maintenance and/or asymmetric cell division of neural progenitor cells, and a mammalian Musashi protein is expressed in various epithelial stem/progenitor cells, including gut, stomach, and mammary gland. Thus, we hypothesized that Musashi might be expressed in stem cells and early progenitor cells of HF epithelium. Reverse transcriptase-polymerase chain reaction and immunoblotting identified Musashi-1 (Msi-1) and Musashi-2 (Msi-2) mRNA and protein in cultured mouse keratinocytes, but only Msi-1 was identified in human keratinocytes. In mice, immunohistochemical studies showed that Msi-1 and Msi-2 were expressed in the epidermis and HFs from E14.5 until adulthood. In the early anagen phase, Msi-1 and Msi-2 were expressed in the bulge and secondary germ cells and subsequently in inner root sheath (IRS) cells, especially the middle IRS cells, during the late anagen phase. In human skin, Msi-1 was detected in fetal HF cells but not in adult HFs. These observations suggest that Musashi functions not only in the asymmetric division of early progenitor cells but also in the differentiation of IRS cells during HF development and hair cycle progression.

Helicobacter Pylori Infection Induces Candidate Stem Cell Marker Musashi-1 in the Human Gastric Epithelium

“…It is highly expressed in neural stem cells and has been suggested to play an important role in the selfrenewing activity and survival of such immature cells [3][4][5][6][7]. The expression of Msi-1, a mammalian neural RNAbinding protein, is regulated concurrently with cell differentiation and growth [4][5][6][7][8][9]. Msi-1 is believed to have a critical function in posttranscriptional gene regulation, such as stabilization, splicing, and translational control of mRNA [6,7,9].…”

The oncogenic RNA-binding protein Musashi1 is regulated by tumor suppressor miRNAs

“…12 Msi1 defines a population of multipotent stem cells in the brain, intestinal crypt cells, breast and hair follicles. [13][14][15][16][17][18][19][20] Msi1 has been determined to be highly expressed in several malignancies, such as glioblastoma Musashi1 (Msi1) is an evolutionarily conserved RNA-binding protein that has been implicated in processes like stem cell fate, nervous system development and tumorigenesis via its activities as a specific regulator of translation. While Msi1 is barely detected in normal adult tissue, it has been observed to be highly expressed in numerous tumor types (e.g., breast, colon, medulloblastoma, glioblastoma, et cetera).…”

Notch Signaling in Hair Follicle Development

“…Molecular biological studies revealed that in mouse Msi1 in these cells controls the Notch signaling pathway through translational reduction of the m-Numb protein, an inhibitor of the Notch pathway, and thereby maintains the stem/progenitor cell status (19). Interestingly, expression of Msi1 was also observed in many types of somatic stem cells in adult tissues, e.g., eye (20), intestine (21), stomach (22), mammary gland (23), and hair follicle (24). Furthermore, significant expression of the protein was observed in proliferative cell populations of tumor tissues (25)(26)(27).…”