School of Biomedical Sciences cordially invites you to join the following Post-doctoral Fellow (PDF) Seminar:

Date: 3 December 2024 (Tuesday)
Time: 4:00 pm – 4:30 pm
Venue: Lecture Theatre 3, G/F, William M.W. Mong Block, 21 Sassoon Road
Host: Dr. Haifeng Fu

Light refreshments will be served. Please register via the below link by 2 December 2024 (Monday):
Registration: https://hku.au1.qualtrics.com/jfe/form/SV_1H5HJkrD0Zq4TlA

Re-engineering the methylation reader function of KLF4 enables pluripotency induction without the SOX2/OCT4 duo
Dr. Ya Gao (Post-doctoral Fellow)

[Supervisor: Professor Ralf Jauch]

Pluripotency reprogramming is a well-established method, but the epigenetic status and developmental potential of induced pluripotent stem cells (iPSCs) vary with cell sources, techniques, and factor cocktails. KLF4, a pioneer transcription factor, directs reprogramming towards iPSCs by binding to silenced chromatin, such as methylated CpG and nucleosome core particles. To enhance KLF4’s function in reprogramming activity, we designed saturation mutagenesis libraries targeting key positions for its binding to methylated-DNA. Through pooled screens in mouse pluripotency reprogramming, we identified evolved KLF4 (eKLF4) variants that alter the reprogramming activity of wild-type KLF4. Notably, two double mutants in KLF4 enable iPSC generation without the essential SOX2/OCT4 duo. iPSCs derived from eKLF4 and c-MYC (eKM) exhibit all molecular, cellular and functional characteristics of embryonic stem cells. Mechanistically, eKLF4 activates mesenchymal-to-epithelial transition and early pluripotency markers, and drives demethylation and opens chromatin regions more effectively than wild-type KLF4. In vitro, eKLF4 shows a higher affinity for the methylated DNA element. Functional enhancements of KLFs optimizes strategies for generating functional cell types for personalized regenerative medicine.

All are welcome.