DataVXAdvanced SciencePaper
journal article·2023-01Open access

Podocalyxin‐Like Protein 1 Regulates Pluripotency through the Cholesterol Biosynthesis Pathway

Wei‐Ju Chen, Wei‐Kai Huang, Sarshan R. Pather, Wei‐Fang Chang, Li‐Ying Sung, Han‐Chung Wu, Mei‐Ying Liao, Chi‐Chiu Lee, Hsuan‐Hui Wu, Chung‐Yi Wu, Kuo‐Shiang Liao, Chun‐Yu Lin, Shang‐Chih Yang, Hsuan Lin, Pei‐Lun Lai, Chi‐Hou Ng, Chun‐Mei Hu, I‐Chih Chen, Chi‐Hsuan Chuang, Chien‐Ying Lai, Po‐Yu Lin, Yueh‐Chang Lee, Scott C. Schuyler, Axel Schambach, Frank Leigh Lu, Jean Lu

Advanced Science· Volume 10· Issue 1
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Source abstract

Abstract

Abstract 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.
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Research context

OpenAlex topics: Pluripotent Stem Cells Research · Renal and related cancers · CRISPR and Genetic Engineering

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

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

Center for Genomic Medicine Massachusetts General Hospital Boston MA 02114 USA

Cell and Molecular Biology Graduate Group Perelman School of Medicine University of Pennsylvania Philadelphia PA 19104 USA

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

Institute of Cellular and Organismic Biology Academia Sinica Taipei 11529 Taiwan

Biomedical Translation Research Center (BioTReC) Academia Sinica Taipei 11529 Taiwan

Department of Ophthalmology Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien 97004 Taiwan

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

Institute of Experimental Hematology Hannover Medical School 30625 Hannover Germany

Department of Pediatrics National Taiwan University Hospital and National Taiwan University Medical College Taipei 10051 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

Funding

Academia Sinica · Ministry of Science and Technology · Chang Gung Memorial Hospital

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