title: The Universal 3D3 Antibody of Human PODXL Is Pluripotent Cytotoxic, and Identifies a Residual Population After Extended Differentiation of Pluripotent Stem Cells.
abstract: Podocalyxin-like protein (PODXL) is a member of CD34 family proteins. It is the protein that carries many post-translational epitopes responsible for various pluripotent surface markers including TRA-1-60, TRA-1-81, GCTM2, GP200, and mAb84. However, PODXL has not attracted the attention of stem cell biologists. Here, we report several features of PODXL mRNA and protein in pluripotent stem cells. Similar to the modification-dependent pluripotent epitopes, PODXL transcripts and carrier protein are also features of pluripotency. PODXL is highly expressed in early human embryos from oocytes up to four-cell stages. During reprogramming of human cells to pluripotency, in contrast to TRA-1-60 and TRA-1-81, PODXL is activated by KLF4 at a very early time of reprogramming. Although TRA-1-60 and TRA-1-81 are completely lost upon differentiation, a residual PODXL(+) population exists even after extended differentiation and they were identified by the universal human PODXL epitope 3D3. Unlike TRA-1-60 and TRA-1-81 epitopes that are unique to primate pluripotent stem cells (PSCs), PODXL carrier protein can be used as a murine surface marker. Most importantly, antibody to 3D3 epitope causes massive necrosis and apoptosis of human PSCs (hPSCs). We suggest that 3D3 antibody could be employed to eliminate the tumorigenic pluripotent cells in hPSC-derived cells for cell transplantation.
authors.affiliation: 1 Stem Cell Institute, Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham , Birmingham, Alabama.|2 Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham , Birmingham, Alabama.
authors.forename: Lei
authors.initials: L
authors.lastname: Kang
authors.affiliation: 1 Stem Cell Institute, Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham , Birmingham, Alabama.|2 Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham , Birmingham, Alabama.|3 Department of Radiation Oncology, Shandong Cancer Hospital & Institute , Jinan, China .
authors.forename: Chunping
authors.initials: C
authors.lastname: Yao
authors.affiliation: 1 Stem Cell Institute, Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham , Birmingham, Alabama.|2 Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham , Birmingham, Alabama.
authors.forename: Alireza
authors.initials: A
authors.lastname: Khodadadi-Jamayran
authors.affiliation: 1 Stem Cell Institute, Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham , Birmingham, Alabama.|2 Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham , Birmingham, Alabama.|4 Longyan University , Fujian, China .
authors.forename: Weihua
authors.initials: W
authors.lastname: Xu
authors.affiliation: 1 Stem Cell Institute, Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham , Birmingham, Alabama.|2 Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham , Birmingham, Alabama.
authors.forename: Ruowen
authors.initials: R
authors.lastname: Zhang
authors.affiliation: 2 Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham , Birmingham, Alabama.
authors.forename: Nilam Sanjib
authors.initials: NS
authors.lastname: Banerjee
authors.affiliation: 1 Stem Cell Institute, Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham , Birmingham, Alabama.|2 Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham , Birmingham, Alabama.
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Chang
authors.affiliation: 2 Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham , Birmingham, Alabama.
authors.forename: Louise T
authors.initials: LT
authors.lastname: Chow
authors.affiliation: 1 Stem Cell Institute, Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham , Birmingham, Alabama.|2 Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham , Birmingham, Alabama.
authors.forename: Tim
authors.initials: T
authors.lastname: Townes
authors.affiliation: 1 Stem Cell Institute, Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham , Birmingham, Alabama.|2 Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham , Birmingham, Alabama.
authors.forename: Kejin
authors.initials: K
authors.lastname: Hu
mesh_terms: D000818:Animals; D000906:Antibodies / Q000633:toxicity*; D017209:Apoptosis; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D000939:Epitopes / Q000276:immunology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D051379:Mice; D012795:Sialoglycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D000906:Antibodies; D000939:Epitopes; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D012795:Sialoglycoproteins; C001643:podocalyxin