Musashi2 is required for the self-renewal and pluripotency of embryonic stem cells

Erin L. Wuebben, Sunil K. Mallanna, Jesse L. Cox, A Angie Rizzino

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Recent studies have shown that the RNA binding protein Musashi 2 (Msi2) plays important roles during development. Msi2 has also been shown to be elevated in several leukemias and its elevated expression has been linked with poorer prognosis in these cancers. Additionally, in embryonic stem cells (ESC) undergoing the early stages of differentiation, Msi2 has been shown to associate with the transcription factor Sox2, which is required for the self-renewal of ESC. These findings led us to examine the effects of Msi2 on the behavior of ESC. We determined that ESC express two isoforms of Msi2, the larger canonical isoform (isoform 1) and a shorter, splice-variant isoform (isoform 2). Using multiple shRNA lentiviral vectors, we determined that knockdown of Msi2 disrupts the self-renewal of ESC and promotes their differentiation into cells that express markers associated with mesoderm, ectoderm, and trophectoderm. Moreover, our studies indicate that the extent of differentiation and the loss of self-renewal capacity correlate with the levels to which Msi2 levels were decreased. We extended these findings by engineering ESC to inducibly express either Msi2 isoform1 or isoform 2. We determined that ectopic expression of Msi2 isoform 1, but not isoform 2, enhances the cloning efficiency of ESC. In addition, we examined how Msi2 isoform 1 and isoform 2 affect the differentiation of ESC. Interestingly, ectopic expression of either Msi2 isoform 1 or isoform 2 does not affect the pattern of differentiation induced by retinoic acid. Finally, we show that ectopic expression of either isoform 1 or isoform 2 is not sufficient to block the differentiation that results from the knockdown of both isoforms of Msi2. Thus, it appears that both isoforms of Msi2 are required for the self-renewal of ESC.

Original languageEnglish (US)
Article numbere34827
JournalPloS one
Volume7
Issue number4
DOIs
StatePublished - Apr 4 2012

Fingerprint

embryonic stem cells
Embryonic Stem Cells
Stem cells
Protein Isoforms
RNA-binding proteins
retinoic acid
leukemia
cell differentiation
prognosis
molecular cloning
engineering
transcription factors
Ectoderm
RNA-Binding Proteins
Cloning
neoplasms
Mesoderm
Tretinoin
Small Interfering RNA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Musashi2 is required for the self-renewal and pluripotency of embryonic stem cells. / Wuebben, Erin L.; Mallanna, Sunil K.; Cox, Jesse L.; Rizzino, A Angie.

In: PloS one, Vol. 7, No. 4, e34827, 04.04.2012.

Research output: Contribution to journalArticle

Wuebben, Erin L. ; Mallanna, Sunil K. ; Cox, Jesse L. ; Rizzino, A Angie. / Musashi2 is required for the self-renewal and pluripotency of embryonic stem cells. In: PloS one. 2012 ; Vol. 7, No. 4.
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