Musashi-2 controls cell fate, lineage bias, and TGF-β signaling in HSCs

Abstract

Musashi-2 is an important regulator of the hematopoietic stem cell translatome and balances HSC homeostasis and lineage bias.

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

“…Zhang et al 24 proposed that Msi2 modulated leukemic cell proliferation and leukemogenesis involving the MAPK signaling pathway. Park et al 25 identified a novel link between Msi2 and TGF-β signaling pathway in regulating HSC translatome and balancing HSC homeostasis. Wang et al 26 uncovered that Msi2 promotes HCC cell invasion and progression via the Wnt/β-catenin signaling pathway.…”

Musashi2 sustains the mixed-lineage leukemia–driven stem cell regulatory program

“…We previously mapped the direct MSI2 RNA binding targets by high-throughput sequencing and cross-linking immunoprecipitation (HITS-CLIP) using a FLAG-tagged version of MSI2 or a control vector in K562 (CML-BC) cells (16). As we reported, MSI2 binds to cellular targets that are associated with a variety of cellular pathways, including metabolism, mRNA regulation, and MYC.…”

“…These findings suggest that increased expression of MSI2 may predict aggressiveness in a variety of cancers. In summary, MSI2 expression was found to be an independent adverse prognostic marker in AML and is a critical regulator of HSC maintenance, which contributes to the pathogenesis of leukemia when dysregulated (14)(15)(16)(17)(18)(19).…”

“…To establish a model to study Msi2 and its contribution to myeloid leukemia, we have used the Msi2 conditional knockout mice that we previously crossed (Msi2 fl/fl ) into an Mx1-Cre background to generate the Msi2 Δ/Δ allele after treatment with polyinositol-polycytosine (pIpC) allowing for conditional deletion within the hematopoietic compartment (16). In order to test whether Msi2 is critical for MLL-AF9-mediated initiation, we transduced control Msi2 fl/fl and Msi2 Δ/Δ Lin-Sca-1 + c-Kit + cells (LSKs) with MLL-AF9-expressing retroviruses coexpressing GFP (Figure 2A).…”

“…additional set of relevant gene sets (92 gene sets from our experimentally derived or published hematopoietic self-renewal and differentiation signatures) (16,38). We found 50 gene sets that were enriched for downregulated genes in Msi2 Δ/Δ LSCs and 233 gene sets that were enriched in genes upregulated in Msi2 Δ/Δ LSCs (Supplemental Tables 4 and 5).…”