Induced Pluripotent Stem Cells Derived From Two Idiopathic Azoospermia Patients Display Compromised Differentiation Potential for Primordial Germ Cell Fate

Frontiers in Cell and Developmental Biology
Fang FangChengliang Xiong

Abstract

At present, the etiology of most non-obstructive azoospermia (NOA) remains unclear. In vitro generation of patient-specific induced pluripotent stem cells (iPSCs) is an effective approach for exploring the mechanisms of human disease. Here, we established iPSCs from two patients with idiopathic NOA and differentiated them into primordial germ cell-like cells (PGCLCs) in vitro. Compared with iPSCs derived from normal fertile men, the NOA patient-specific iPSCs show decreased efficiency of PGCLC formation in vitro. Particularly, the embryoids derived from NOA patient-specific iPSCs show defects in the expression of early primordial germ cell (PGC) genes. The transcriptome analysis reveals the expression patterns of key human PGC genes are generally similar in PGCLCs differentiated from all iPSC lines, and the differentially expressed genes were enriched with gene ontology (GO) of cell cycle and apoptosis regulation. Moreover, the PGCLCs derived from NOA patient-specific iPSCs might have initiated epigenetic reprogramming at a very early stage. Thus, the NOA patient-specific iPSCs exhibit poor response to germ cell induction in vitro, which may be related to the regulation of apoptotic process. These findings provide a foundation ...Continue Reading

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Datasets Mentioned

BETA
GSE63818
GSE126009

Methods Mentioned

BETA
Fluorescence-activated
flow cytometry
Fluorescence-activated cell sorting
FACS
PCA
RNA-seq

Software Mentioned

STAR ( Spliced Transcripts Alignment to a Reference )
iMeLCs
HTSeq
Prism Graphic
Database for Annotation , Visualization and Integrated Discove...
Trim Galore
DESeq2

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis