MS4A3 regulates hematopoietic myeloid differentiation through ROS/TGF-β/p38MAPK pathway

Related Experiment Video

Updated: Jun 7, 2025

Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells
10:21

Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells

Published on: February 21, 2018

9.9K

Yinping Dong1, Tongpeng Yue1, Xinyue Wang1

  • 1Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192, China.

International Immunopharmacology
|November 12, 2024
PubMed

Insights

MS4A3 overexpression promotes myeloid differentiation skewing by activating the ROS/p38MAPK/TGFβ pathway, impacting hematopoietic homeostasis. This finding clarifies MS4A3

Area of Science:

  • Hematology
  • Molecular Biology
  • Cell Biology

Background:

  • Hematopoietic homeostasis depends on precise regulation of hematopoietic stem cells.
  • Myeloid differentiation disorders are linked to leukemia, highlighting the need to understand myeloid differentiation regulators.
  • MS4A3 is increasingly expressed in myeloid cells, suggesting a potential role in myeloid differentiation.

Purpose of the Study:

  • To elucidate the mechanism and role of MS4A3 in hematopoietic myeloid differentiation.
  • To investigate the effect of MS4A3 overexpression and knockdown on myeloid differentiation.

Main Methods:

  • Utilized K562 cell lines with MS4A3 overexpression (oeMS4A3) and MS4A3 knockdown (shMS4A3).
  • Investigated the impact of inhibiting reactive oxygen species (ROS), TGF-β, and p38MAPK pathways.
  • Conducted in vivo experiments using MS4A3 knockout mice.

Main Results:

  • MS4A3 overexpression in K562 cells led to increased myeloid differentiation and G0/G1 cell cycle arrest.
  • Inhibition of ROS, TGF-β, and p38MAPK pathways attenuated the myeloid differentiation skewing in oeMS4A3 cells.
  • MS4A3 knockout mice showed a slight tendency towards suppressed myeloid differentiation.

Conclusions:

  • MS4A3 overexpression promotes myeloid differentiation skewing via activation of the ROS/p38MAPK/TGFβ pathway.
  • This study highlights the critical role of MS4A3 in regulating hematopoietic myeloid differentiation.
  • Findings provide insights into potential therapeutic targets for myeloid differentiation disorders.
Keywords:
MS4A3Myeloid skewingROSTGF-βp38MAPK

More Related Videos

Retroviral Infection of Murine Embryonic Stem Cell Derived Embryoid Body Cells for Analysis of Hematopoietic Differentiation11:40

Retroviral Infection of Murine Embryonic Stem Cell Derived Embryoid Body Cells for Analysis of Hematopoietic Differentiation

Published on: October 20, 2014

8.5K
Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling07:49

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling

Published on: August 3, 2018

11.3K

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

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...
7.2K
Regulation of Hematopoietic Stem Cells01:01

Regulation of Hematopoietic Stem Cells

All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
3.1K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.2K
Master Transcription Regulators02:23

Master Transcription Regulators

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
Role of Hematopoietic Growth Factors01:28

Role of Hematopoietic Growth Factors

Hematopoietic growth factors are molecules that regulate the differentiation rate of hematopoietic stem cells (HSCs). Erythropoietin (EPO), primarily produced by the kidneys, plays a crucial role in erythrocyte production. When oxygen levels in the blood are low, EPO is released into the bloodstream, reaching the bone marrow, where it stimulates HSCs to differentiate and mature into erythrocytes, which are vital for oxygen transport.
Thrombopoietin (TPO), mainly released by the liver,...
1.3K