| First Author | Zhao Y | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 9 | Pages | 107540 |
| PubMed ID | 37649699 | Mgi Jnum | J:357682 |
| Mgi Id | MGI:7528333 | Doi | 10.1016/j.isci.2023.107540 |
| Citation | Zhao Y, et al. (2023) mTORC2 orchestrates monocytic and granulocytic lineage commitment by an ATF5-mediated pathway. iScience 26(9):107540 |
| abstractText | Myeloid hematopoiesis is a finely controlled consecutive developmental process, which is essential to maintain peripheral innate immune homeostasis. Herein, we found that Rictor deletion caused the remarkable reduction of granulocyte-monocyte progenitors (GMPs), monocytes, and macrophages, while the levels of neutrophils were unaffected. Adoptive transfer of Rictor-deleted GMPs or common myeloid progenitors (CMPs) in syngeneic mice showed poor re-constitution of monocytes compared to wild-type GMPs or CMPs. In addition to decreasing the proliferation of CMPs/GMPs, Rictor deletion preferentially inhibited Ly6C(+) monocyte differentiation, while enhancing neutrophil differentiation, as determined by colony formation assays. mTORC2 promotes monocyte development by downregulation of the AKT-Foxo4-activating transcription factor 5 (ATF5)-mitochondrial unfolded protein response (mtUPR) pathway. Genetic overexpression of ATF5 or exposure to ethidium bromide significantly rescued monocyte/macrophage differentiation defects of Rictor-deficient myeloid progenitors. Therefore, Rictor is required for CMP/GMP proliferation and acts as an important switch to balance monocytic and granulocytic lineage commitment in bone marrow. |
