The RNA-binding protein Musashi is required intrinsically to maintain stem cell identity

Abstract

A key goal of regenerative medicine is an understanding of the genetic factors that define the properties of stem cells. However, stem cell research in mammalian tissue has been hampered by a paucity of stem cell-specific markers. Although increasing evidence suggests that members of the Musashi (Msi) family of RNA-binding proteins play important functions in progenitor cells, it remains unclear whether there is a stem cell-autonomous requirement for Msi because of an inability to distinguish stem cells from earlylineage cells in mammalian tissues. Here, using the Drosophila testis as a model system for the study of stem cell regulation, we show specific evidence for a cell-autonomous requirement for Msi family proteins in regulating stem cell differentiation, leading to the identification of an RNA-binding protein required for spermatogonial stem cell maintenance. We found that loss of Msi function disrupts the balance between germ-line stem cell renewal and differentiation, resulting in the premature differentiation of germ-line stem cells. Moreover, we found that, although Msi is expressed in both somatic and germ cells, Msi function is required intrinsically in stem cells for maintenance of stem cell identity. We also discovered a requirement for Msi function in male meiosis, revealing that Msi has distinct roles at different stages of germ cell differentiation. We describe the complementary expression patterns of the murine Msi paralogues Msi1 and Msi2 during spermatogenesis, which support the idea of distinct, evolutionarily conserved roles of Msi.spermatogenesis ͉ Drosophila ͉ testis ͉ spermatocyte ͉ translation

EVI1 overexpression in t(3;17) positive myeloid malignancies results from juxtaposition of EVI1 to the MSI2 locus at 17q22

“…MSI2 plays a role in post-transcriptional gene regulation and in maintaining stem cell status, 18 and involvement of MSI2 in myeloid leukemias has previously been reported in 2 CML patients, one of which carried a MSI2/HOXA9 fusion gene. 19 In our patient series however, no MSI2/EVI1 fusion gene could be detected in RT-PCR analysis.…”

Progenitor stem cell marker expression by pulmonary carcinomas

“…Some of the markers included are: CD133, a primitive hematopoietic and stem cell marker that shows restricted membranous expression in some epithelial cells and may be a marker of tumor-initiating cells; 8,9 Musashi-1, an RNA-binding protein that seems to be present in cells undergoing asymmetric division and required for the maintenance of stem cell identity; [10][11][12] Musashi-2, also an RNA-binding protein that belongs to the same family of proteins as Musashi-1; 12 and p21, a cyclindependent kinase inhibitor of the cell cycle. This protein has been implicated in the maintenance of the quiescence state of hematopoietic stem cells.…”

Musashi-2 promotes migration and invasion in bladder cancer via activation of the JAK2/STAT3 pathway

“…6 As a RNA-binding protein, Msi2 is linked to stem cells and contribute to asymmetric cell division control, germ and somatic stem cell function, and cell fate determination in a number of tissues. 7 Msi2 has been shown to contribute to specific neuronal lineages generation and maintenance. 8 In addition, Msi2 has been demonstrated as an important modulator of hematopoietic stem cells (HSCs) and their progenitors.…”