Homeostatic control of stem cell activity during intestinal regeneration.

NF-Y functions as a transcriptional repressor that maintains intestinal stem cell quiescence by restricting EGFR signaling components, and its loss enhances ISC proliferation and accelerates tumor progression.

• Why it matters: Rapid ISC proliferation during intestinal regeneration must be balanced to prevent hyperproliferation, but the transcriptional “brake” limiting growth signaling was unclear.
• What they did: The study identified NF-Y as a repressor that occupies promoters of EGFR pathway components (Egfr, Mkp3, Raf, Ras, pnt) in a Nej/p300-dependent manner, then tested effects of NF-Y loss on proliferation and tumor progression.
• The result: NF-Y with Nej restricts Egfr expression and suppresses hyperproliferation, implying a homeostatic and disease-linked mechanism for controlling stem cell activity.

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