Aberrant Gene Expression Profiles in Pluripotent Stem Cells Induced from Fibroblasts of a Klinefelter Syndrome Patient

Yu Ma,Peng Li,Chun Li,Fan Tang,Junjie Gu,Ying Jin,Chunliang Li,Shi Yang,Zheng Li,Ping Ping

doi:10.1074/jbc.m112.380204

Abstract

Klinefelter syndrome (KS) is the most common male chromosome aneuploidy. Its pathophysiology is largely unexplained due to the lack of adequate models. Here, we report the derivation of induced pluripotent stem cell (iPSCs) lines from a KS patient with a karyotype of 47, XXY. Derived KS-iPSCs meet all criteria of normal iPSCs with the potential for germ cell differentiation. Although X chromosome inactivation occurs in all KS-iPSCs, genome-wide transcriptome analysis identifies aberrantly expressed genes associated with the clinical features of KS. Our KS-iPSCs can serve as a cellular model for KS research. Identified genes may become biomarkers for early diagnosis or potential therapeutic targets for KS and significantly accelerate the understanding, diagnosis, and treatment of Klinefelter syndrome.

Highlights

Pathophysiology for Klinefelter syndrome (KS) is poorly explained due to the lack of adequate models
The human embryonic stem cell-like colonies were picked on day 12 of infection and expanded to establish the stable induced pluripotent stem cells (iPSCs) lines
There was no discernible difference in terms of reprogramming speed and efficiency between normal fibroblasts (N-fs) and KS fibroblasts (KS-fs). iPSCs from both N-fs and KS-fs exhibited a typical morphology of human embryonic stem cell (hESC) and had the same karyotypes as their cognate fibroblasts, suggesting the maintenance of initial karyotypes throughout the reprogramming process (Fig. 1, E and F)

Summary

Background

Pathophysiology for Klinefelter syndrome (KS) is poorly explained due to the lack of adequate models. We report the derivation of induced pluripotent stem cell (iPSCs) lines from a KS patient with a karyotype of 47, XXY. Identified genes may become biomarkers for early diagnosis or potential therapeutic targets for KS and significantly accelerate the understanding, diagnosis, and treatment of Klinefelter syndrome. The advent of induced pluripotent stem cells (iPSCs) by defined transcriptional factors, those derived from patients, provides a new and attractive alternative for the in vitro disease model [7, 8]. We generated four lines of iPSCs from foreskin fibroblast cells of a KS patient with the 47, XXY karyotype and explored their potential usage for modeling the development of KS disease in vitro. IPSC Lines of a Klinefelter Syndrome Patient understanding of this particular disease and identify potential new targets for its treatment

EXPERIMENTAL PROCEDURES

RESULTS

DISCUSSION