PRDM14 is expressed in germ cell tumors with constitutive overexpression altering human germline differentiation and proliferation

Joanna J Gell; Jasmine Zhao; Di Chen; Timothy J Hunt; Amander T Clark

doi:10.1016/j.scr.2017.12.016

PRDM14 is expressed in germ cell tumors with constitutive overexpression altering human germline differentiation and proliferation

Stem Cell Res. 2018 Mar:27:46-56. doi: 10.1016/j.scr.2017.12.016. Epub 2018 Jan 4.

Authors

Joanna J Gell¹, Jasmine Zhao², Di Chen³, Timothy J Hunt³, Amander T Clark⁴

Affiliations

¹ Department of Pediatrics, Division of Hematology-Oncology, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Los Angeles, CA 90095, USA; David Geffen School of Medicine, Los Angeles, CA 90095, USA.
² Department of Molecular, Cell and Developmental Biology, Los Angeles, CA 90095, USA; University of California Los Angeles, Los Angeles, CA 90095, USA.
³ Department of Molecular, Cell and Developmental Biology, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Los Angeles, CA 90095, USA; University of California Los Angeles, Los Angeles, CA 90095, USA.
⁴ Department of Molecular, Cell and Developmental Biology, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Los Angeles, CA 90095, USA; University of California Los Angeles, Los Angeles, CA 90095, USA. Electronic address: clarka@ucla.edu.

Abstract

Germ cell tumors (GCTs) are a heterogeneous group of tumors occurring in gonadal and extragonadal locations. GCTs are hypothesized to arise from primordial germ cells (PGCs), which fail to differentiate. One recently identified susceptibility loci for human GCT is PR (PRDI-BF1 and RIZ) domain proteins 14 (PRDM14). PRDM14 is expressed in early primate PGCs and is repressed as PGCs differentiate. To examine PRDM14 in human GCTs we profiled human GCT cell lines and patient samples and discovered that PRDM14 is expressed in embryonal carcinoma cell lines, embryonal carcinomas, seminomas, intracranial germinomas and yolk sac tumors, but is not expressed in teratomas. To model constitutive overexpression in human PGCs, we generated PGC-like cells (PGCLCs) from human pluripotent stem cells (PSCs) and discovered that elevated expression of PRDM14 does not block early PGC formation. Instead, we show that elevated PRDM14 in PGCLCs causes proliferation and differentiation defects in the germline.

Keywords: Cell differentiation; Germ cell tumor; PRDM14; Primordial germ cell; Proliferation.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Cell Differentiation / genetics
Cell Differentiation / physiology
Cell Proliferation / genetics
Cell Proliferation / physiology
Child
Child, Preschool
DNA-Binding Proteins
Female
Germ Cells
Humans
Infant
Male
Neoplasms, Germ Cell and Embryonal / genetics
Neoplasms, Germ Cell and Embryonal / metabolism*
Pluripotent Stem Cells / metabolism
RNA-Binding Proteins
Repressor Proteins / metabolism*
Teratoma / metabolism
Transcription Factors
Young Adult

Substances

DNA-Binding Proteins
PRDM14 protein, human
RNA-Binding Proteins
Repressor Proteins
Transcription Factors

Abstract

Publication types

MeSH terms

Substances

Grants and funding