Related Experiment Video
Updated: May 9, 2026
10:21
Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells
Published on: February 21, 2018
Positive feedback between PU.1 and the cell cycle controls myeloid differentiation
Hao Yuan Kueh1, Ameya Champhekar, Ameya Champhekhar
1Division of Biology, California Institute of Technology, Pasadena, CA, USA. kueh@caltech.edu
Science (New York, N.Y.)
|July 23, 2013
Summary
Cell cycle duration stabilizes stem cell differentiation through positive feedback. Transcription factor PU.1 accumulation in macrophages, driven by longer cell cycles, controls cell fate.
Area of Science:
- Cellular and Molecular Biology
- Developmental Biology
- Immunology
Background:
- Positive-feedback loops are crucial for stem cell differentiation.
- Multiple mechanisms can generate positive feedback in gene regulatory circuits.
- The transcription factor PU.1 plays a key role in lymphoid and myeloid lineage commitment.
Purpose of the Study:
- To investigate the specific feedback mechanisms by which the transcription factor PU.1 regulates B cell and macrophage differentiation.
- To elucidate the role of cell cycle dynamics in PU.1-mediated cell fate decisions.
- To understand how positive autoregulation contributes to stable cell differentiation.
Main Methods:
- Quantitative live-cell imaging to monitor PU.1 levels and cell cycle progression in differentiating cells.
- Experimental manipulation of exogenous PU.1 expression in progenitor cells.
- Mathematical modeling to analyze the feedback architecture and its impact on cell cycle duration and differentiation stability.
Main Results:
- Developing B cells downregulate PU.1 by reducing transcription.
- Developing macrophages accumulate PU.1 by extending cell cycle duration, creating a stable, slow-dividing state.
- Exogenous PU.1 expression induces cell cycle lengthening, demonstrating positive feedback between PU.1 and cell cycle duration.
- Mathematical models confirmed that cell cycle-coupled feedback stabilizes differentiated cell states.
Conclusions:
- Cell cycle duration is an integral component of the positive autoregulatory circuit controlling PU.1 levels.
- This cell cycle-coupled feedback mechanism effectively stabilizes differentiated cell fates, specifically in macrophages.
- The interplay between transcription factor levels and cell cycle kinetics provides a robust strategy for cell fate determination in stem cell differentiation.
More Related Videos
Related Concept Videos
01:15Differentiation of Common Myeloid Progenitor Cells
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...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:21Lineage Commitment
Commitment is the process whereby stem cells:
02:38Mitogens and the Cell Cycle
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
02:36Cells Coordinate Growth and Proliferation
Cell size is a significant factor impacting cellular design, function, and fitness. There exists some internal coordination by which cells double their masses before division, thus, achieving homeostasis. Coordination between cell growth and proliferation depends on the checkpoints in between cell cycle phases. Loss of coordination or failure in the checkpoint mechanism can drive the cell to uncontrolled growth and loss of cellular function. Like dividing cells that coordinate cellular growth,...
01:23Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.