TAF4b and TAF4 differentially regulate mouse embryonic stem cells maintenance and proliferation

Area of Science:

• Molecular Biology
• Developmental Biology
• Stem Cell Biology

Background:

• TAF4b is a subunit of the general transcription factor TFIID, highly expressed in embryonic stem cells (ESCs).
• Its paralog, TAF4, is ubiquitously expressed and plays different roles in development.

Purpose of the Study:

• To investigate the function of TAF4b in ESCs and compare it with TAF4.
• To identify TAF4b-regulated genes involved in ESC self-renewal and cell cycle control.

Main Methods:

• Knockdown (KD) of TAF4b and TAF4 in ESCs.
• Assessment of cell morphology, self-renewal markers (alkaline phosphatase), and differentiation.
• Analysis of gene expression, cell proliferation, and cell cycle progression.
• Co-immunoprecipitation to study protein interactions.

Main Results:

• TAF4b depletion in ESCs caused morphological changes and reduced self-renewal markers.
• TAF4 KD stabilized ESC stemness and delayed differentiation.
• TAF4b promoted ESC proliferation and cell cycle progression, while TAF4 inhibited it.
• TAF4b regulates ESC-specific genes like Sohlh2 and Yes1, which are also Oct4 targets.
• TAF4b, but not TAF4, interacts with Oct4.

Conclusions:

• TAF4b cooperates with Oct4 to maintain ESC self-renewal and regulate specific target genes.
• TAF4 plays a role in later embryonic development, contrasting with TAF4b's function in ESCs.