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Related Experiment Video

Updated: May 20, 2026

In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells

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Published on: January 20, 2019

C/EBPα bypasses cell cycle-dependency during immune cell transdifferentiation.

Alessandro Di Tullio¹, Thomas Graf

¹Gene Regulation, Stem Cells and Cancer Program, Center for Genomic Regulation and Pompeu Fabra University, Barcelona, Spain.

Cell Cycle (Georgetown, Tex.)

|July 10, 2012

Summary

Cell division is not essential for converting pre-B cells into macrophages using transcription factors C/EBPα or C/EBPβ. High C/EBPα levels accelerate differentiation and cell cycle arrest, differing from induced pluripotent stem cell reprogramming.

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Area of Science:

Cell Biology
Developmental Biology
Transcriptional Regulation

Background:

Earlier studies demonstrated efficient conversion of pre-B cells to macrophage-like cells via transcription factor C/EBPα or C/EBPβ overexpression.
Investigating the role of cell division in this transdifferentiation process is crucial for understanding cellular reprogramming mechanisms.

Purpose of the Study:

To determine the necessity of cell division during C/EBP-induced transdifferentiation of pre-B cells into macrophages.
To compare the reprogramming kinetics and requirements with those of induced pluripotent stem cell (iPSC) generation.

Main Methods:

Utilized inducible pre-B cell lines for controlled C/EBPα and C/EBPβ expression.
Employed BrdU incorporation assays to track DNA synthesis and cell cycle progression.
Performed p53 knockdown experiments and time-lapse microscopy to analyze cell division and differentiation.

Main Results:

The majority of C/EBPα-induced cells and all C/EBPβ-induced cells underwent DNA synthesis (BrdU incorporation).
Inhibition of DNA synthesis partially impaired C/EBPα-induced transdifferentiation, but sorted cell cycle phases showed similar reprogramming kinetics.
A subset of non-dividing cells exhibited faster differentiation, particularly with high C/EBPα levels, suggesting accelerated growth arrest.

Conclusions:

Cell cycle traversal is not strictly required for pre-B cell to macrophage transdifferentiation.
High levels of C/EBPα can accelerate both the differentiation process and cell cycle arrest.
The mechanisms underlying transcription factor-induced transdifferentiation and iPSC reprogramming appear to differ significantly.