| First Author | Petkau G | Year | 2018 |
| Journal | Eur J Immunol | Volume | 48 |
| Issue | 6 | Pages | 975-989 |
| PubMed ID | 29505092 | Mgi Jnum | J:263508 |
| Mgi Id | MGI:6164751 | Doi | 10.1002/eji.201747354 |
| Citation | Petkau G, et al. (2018) MiR221 promotes precursor B-cell retention in the bone marrow by amplifying the PI3K-signaling pathway in mice. Eur J Immunol 48(6):975-989 |
| abstractText | Hematopoietic stem cells and lineage-uncommitted progenitors are able to home to the bone marrow upon transplantation and reconstitute the host with hematopoietic progeny. Expression of miR221 in B-lineage committed preBI-cells induces their capacity to home to the bone marrow. However, the molecular mechanisms underlying miR221-controlled bone marrow homing and retention remain poorly understood. Here, we demonstrate, that miR221 regulates bone marrow retention of such B-cell precursors by targeting PTEN, thus enhancing PI3K signaling in response to the chemokine CXCL12. MiR221-enhanced PI3K signaling leads to increased expression of the anti-apoptotic protein Bcl2 and VLA4 integrin-mediated adhesion to VCAM1 in response to CXCL12 in vitro. Ablation of elevated PI3K activity abolishes the retention of miR221 expressing preBI-cells in the bone marrow. These results suggest that amplification of PI3K signaling by miR221 could be a general mechanism for bone marrow residence, shared by miR221-expressing hematopoietic cells. |
