Activation of quiescent stem cells
View Patent ↗Compositions and methods are provided for altering the activation of quiescent stem cells by modulating activity of the microRNA miR-489.
1. A method of altering muscle satellite cell quiescence, the method comprising:
contacting a mammalian muscle satellite cell with a miR 489 inhibitory nucleic acid in a dose effective to down-regulate quiescence of the satellite cell, wherein the satellite cell is activated and proliferates.
2. The method of claim 1 , wherein the nucleic acid is an siRNA or shRNA.
3. The method of claim 1 , wherein the nucleic acid is an antisense oligonucleotide.
4. A method of altering muscle satellite cell quiescence, the method comprising:
contacting by local administration a mammalian muscle-satellite cell with a miR 489 antisense oligonucleotide in a dose effective to down-regulate quiescence of the satellite cell, wherein the satellite cell is activated and proliferates, wherein the antisense oligonucleotide is a modified oligonucleotide that is complementary to miR-489, wherein the oligonucleotide is at least 12 but not more than 25 nucleotides in length and has no more than 2 mismatches over its length compared to an equal length portion of miR-489.
5. The method of claim 4 wherein said modified oligonucleotide comprises a cholesterol conjugate.
6. The method of claim wherein said modified oligonucleotide comprises one or more phosphorothioate linkages.
7. The method of claim 4 wherein said modified oligonucleotide comprises one or more sugar modifications.
8. The method of claim 4 , wherein said muscle satellite cell is contacted in vitro.
9. The method of claim 4 , wherein said muscle stem satellite cell is in vivo.
10. A method of altering muscle satellite cell quiescence, the method comprising:
contacting by local administration a mammalian muscle satellite cell with a miR 489 antisense oligonucleotide in a dose effective to down-regulate quiescence of the satellite cell, wherein the satellite cell is activated and proliferates, wherein the antisense oligonucleotide is a modified oligonucleotide that is complementary to miR-489, wherein the oligonucleotide is at least 12 but not more than 25 nucleotides in length and has no more than 2 mismatches over its length compared to an equal length portion of miR-489; and
monitoring proliferation or differentiation of the muscle satellite cells.