Related Experiment Video
Updated: Jul 17, 2025
10:21
Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells
Published on: February 21, 2018
10.0K
mTORC2 orchestrates monocytic and granulocytic lineage commitment by an ATF5-mediated pathway
Yang Zhao1,2, Chenxu Zhao1,3,4, Han Guo1,3,2
1State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Iscience
|August 31, 2023
Summary
Rictor deletion impairs myeloid progenitor proliferation and monocyte development, disrupting immune homeostasis. This study reveals Rictor
Area of Science:
- Immunology
- Cell Biology
- Developmental Biology
Background:
- Myeloid hematopoiesis is crucial for innate immune homeostasis.
- Granulocyte-macrophage progenitors (GMPs) and common myeloid progenitors (CMPs) are key stem cells.
- The mechanistic target of rapamycin complex 2 (mTORC2) pathway's role in hematopoiesis is under investigation.
Purpose of the Study:
- To investigate the role of Rictor, a component of mTORC2, in myeloid progenitor development and immune cell differentiation.
- To elucidate the molecular mechanisms by which Rictor influences monocyte and neutrophil lineage commitment.
Main Methods:
- Utilized Rictor-deleted mouse models.
- Performed adoptive transfer experiments with Rictor-deleted GMPs and CMPs.
- Conducted colony formation assays to assess progenitor differentiation.
- Analyzed the AKT-Foxo4-ATF5-mtUPR signaling pathway.
Main Results:
- Rictor deletion significantly reduced GMPs, monocytes, and macrophages but did not affect neutrophils.
- Adoptive transfer of Rictor-deleted progenitors showed impaired monocyte reconstitution.
- Rictor deficiency inhibited CMP/GMP proliferation and Ly6C+ monocyte differentiation while enhancing neutrophil differentiation.
- Overexpression of ATF5 or ethidium bromide treatment rescued monocyte differentiation defects.
Conclusions:
- Rictor is essential for CMP/GMP proliferation and proper monocyte development.
- Rictor acts as a critical regulator balancing monocytic and granulocytic lineage commitment.
- The mTORC2-AKT-Foxo4-ATF5-mtUPR pathway is vital for monocyte differentiation.
Related Concept Videos
01:21Lineage Commitment
3.0K
Commitment is the process whereby stem cells:
3.0K
01:15Differentiation of Common Myeloid Progenitor Cells
3.2K
Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
3.2K
01:16TGF - β Signaling Pathway
7.4K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.4K
02:23Master Transcription Regulators
6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
03:03mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
01:22T Cell Activation and Clonal Selection
804
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
804