Podocalyxin-Like Protein 1 Regulates Pluripotency through the Cholesterol Biosynthesis Pathway.

Autor: Chen WJ; Genomics Research Center, Academia Sinica, Genome and Systems Biology Degree Program, College of Life Science, National Taiwan University, Taipei, 10617, Taiwan.; Genomics Research Center, Academia Sinica, Taipei, 11529, Taiwan., Huang WK; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA., Pather SR; Cell and Molecular Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA., Chang WF; Institute of Biotechnology, National Taiwan University, Taipei, 10617, Taiwan., Sung LY; Institute of Biotechnology, National Taiwan University, Taipei, 10617, Taiwan.; Agricultural Biotechnology Research Center, Academia Sinica, Taipei, 11529, Taiwan.; Animal Resource Center, National Taiwan University, Taipei, 10617, Taiwan., Wu HC; Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, 11529, Taiwan.; Biomedical Translation Research Center (BioTReC), Academia Sinica, Taipei, 11529, Taiwan., Liao MY; Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, 11529, Taiwan., Lee CC; Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, 11529, Taiwan., Wu HH; Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, 11529, Taiwan., Wu CY; Genomics Research Center, Academia Sinica, Taipei, 11529, Taiwan., Liao KS; Genomics Research Center, Academia Sinica, Taipei, 11529, Taiwan., Lin CY; Genomics Research Center, Academia Sinica, Taipei, 11529, Taiwan., Yang SC; Genomics Research Center, Academia Sinica, Taipei, 11529, Taiwan., Lin H; Genomics Research Center, Academia Sinica, Taipei, 11529, Taiwan., Lai PL; Genomics Research Center, Academia Sinica, Taipei, 11529, Taiwan., Ng CH; Genomics Research Center, Academia Sinica, Taipei, 11529, Taiwan., Hu CM; Genomics Research Center, Academia Sinica, Taipei, 11529, Taiwan., Chen IC; Genomics Research Center, Academia Sinica, Taipei, 11529, Taiwan., Chuang CH; Genomics Research Center, Academia Sinica, Taipei, 11529, Taiwan., Lai CY; Genomics Research Center, Academia Sinica, Taipei, 11529, Taiwan., Lin PY; Genomics Research Center, Academia Sinica, Taipei, 11529, Taiwan., Lee YC; Department of Ophthalmology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, 97004, Taiwan., Schuyler SC; Department of Biomedical Sciences, College of Medicine, Chang Gung University, Division of Head and Neck Surgery, Department of Otolaryngology, Chang Gung Memorial Hospital, Taoyuan, 33302, Taiwan., Schambach A; Institute of Experimental Hematology, Hannover Medical School, 30625, Hannover, Germany., Lu FL; Department of Pediatrics, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, 10051, Taiwan., Lu J; Genomics Research Center, Academia Sinica, Genome and Systems Biology Degree Program, College of Life Science, National Taiwan University, Taipei, 10617, Taiwan.; Genomics Research Center, Academia Sinica, Taipei, 11529, Taiwan.; National RNAi Platform/ National Core Facility Program for Biotechnology, Taipei, 11529, Taiwan.; Department of Life Science, Tzu Chi University, Hualien, 97004, Taiwan.; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, 11490, Taiwan.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2022 Nov 14, pp. e2205451. Date of Electronic Publication: 2022 Nov 14.
DOI: 10.1002/advs.202205451
Abstrakt: Deciphering signaling mechanisms critical for the extended pluripotent stem cell (EPSC) state and primed pluripotency is necessary for understanding embryonic development. Here, a membrane protein, podocalyxin-like protein 1 (PODXL) as being essential for extended and primed pluripotency, is identified. Alteration of PODXL expression levels affects self-renewal, protein expression of c-MYC and telomerase, and induced pluripotent stem cell (iPSC) and EPSC colony formation. PODXL is the first membrane protein reported to regulate de novo cholesterol biosynthesis, and human pluripotent stem cells (hPSCs) are more sensitive to cholesterol depletion than fibroblasts. The addition of exogenous cholesterol fully restores PODXL knockdown-mediated loss of pluripotency. PODXL affects lipid raft dynamics via the regulation of cholesterol. PODXL recruits the RAC1/CDC42/actin network to regulate SREBP1 and SREBP2 maturation and lipid raft dynamics. Single-cell RNA sequencing reveals PODXL overexpression enhanced chimerism between human cells in mouse host embryos (hEPSCs 57%). Interestingly, in the human-mouse chimeras, laminin and collagen signaling-related pathways are dominant in PODXL overexpressing cells. It is concluded that cholesterol regulation via PODXL signaling is critical for ESC/EPSC.
(© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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