Induced pluripotent stem cells established from a female patient with Xq22 deletion confirm that BEX2 escapes from X‐chromosome inactivation

2020 ◽  
Author(s):  
Keiko Yamamoto‐Shimojima ◽  
Mitsujiro Osawa ◽  
Megumu K. Saito ◽  
Toshiyuki Yamamoto
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Female Patient ◽  
X Chromosome ◽  
Pluripotent Stem Cells ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Induced Pluripotent

scholarly journals Human induced pluripotent stem cells from two azoospermic patients with Klinefelter syndrome show similar X chromosome inactivation behavior to female pluripotent stem cells

2019 ◽  
Vol 34 (11) ◽  
pp. 2297-2310 ◽  
Author(s):  
Sarita Panula ◽  
Magdalena Kurek ◽  
Pankaj Kumar ◽  
Halima Albalushi ◽  
Sara Padrell Sánchez ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Clinical Features ◽  
X Chromosome ◽  
Pluripotent Stem Cells ◽  
Klinefelter Syndrome ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Whole Genome ◽  
Induced Pluripotent

Abstract STUDY QUESTION Does the X chromosome inactivation (XCI) of Klinefelter syndrome (KS)-derived human induced pluripotent stem cells (hiPSCs) correspond to female human pluripotent stem cells (hPSCs) and reflect the KS genotype? SUMMARY ANSWER Our results demonstrate for the first time that KS-derived hiPSCs show similar XCI behavior to female hPSCs in culture and show biological relevance to KS genotype-related clinical features. WHAT IS KNOWN ALREADY So far, assessment of XCI of KS-derived hiPSCs was based on H3K27me3 staining and X-inactive specific transcript gene expression disregarding the at least three XCI states (XaXi with XIST coating, XaXi lacking XIST coating, and XaXe (partially eroded XCI)) that female hPSCs display in culture. STUDY DESIGN, SIZE, DURATION The study used hiPSC lines generated from two azoospermic patients with KS and included two healthy male (HM) and one healthy female donor. PARTICIPANTS/MATERIALS, SETTING, METHODS In this study, we derived hiPSCs by reprograming fibroblasts with episomal plasmids and applying laminin 521 as culture substrate. hiPSCs were characterized by karyotyping, immunocytochemistry, immunohistochemistry, quantitative PCR, teratoma formation, and embryoid body differentiation. XCI and KS hiPSC relevance were assessed by whole genome transcriptomics analysis and immunocytochemistry plus FISH of KS, HM and female fibroblast, and their hiPSC derivatives. MAIN RESULTS AND THE ROLE OF CHANCE Applying whole genome transcriptomics analysis, we could identify differentially expressed genes (DEGs) between KS and HM donors with enrichment in gene ontology terms associated with fertility, cardiovascular development, ossification, and brain development, all associated with KS genotype-related clinical features. Furthermore, XCI analysis based on transcriptomics data, RNA FISH, and H3K27me3 staining revealed variable XCI states of KS hiPSCs similar to female hiPSCs, showing either normal (XaXi) or eroded (XaXe) XCI. KS hiPSCs with normal XCI showed nevertheless upregulated X-linked genes involved in nervous system development as well as synaptic transmission, supporting the potential use of KS-derived hiPSCs as an in vitro model for KS. LIMITATIONS, REASONS FOR CAUTION Detailed clinical information for patients included in this study was not available. Although a correlation between DEGs and the KS genotype could be observed, the biological relevance of these cells has to be confirmed with further experiments. In addition, karyotype analysis for two hiPSC lines was performed at passage 12 but not repeated at a later passage. Nevertheless, since all XCI experiments for those lines were performed between passage 11 and 15 the authors expect no karyotypic changes for those experiments. WIDER IMPLICATIONS OF THE FINDINGS As KS patients have variable clinical phenotypes that are influenced by the grade of aneuploidy, mosaicism, origin of the X chromosome, and XCI ‘escapee’ genes, which vary not only among individuals but also among different tissues within the same individual, differentiated KS hiPSCs could be used for a better understanding of KS pathogenesis. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by grants from the Knut and Alice Wallenberg Foundation (2016.0121 and 2015.0096), Ming Wai Lau Centre for Reparative Medicine (2-343/2016), Ragnar Söderberg Foundation (M67/13), Swedish Research Council (2013-32485-100360-69), the Centre for Innovative Medicine (2–388/2016–40), Kronprinsessan Lovisas Förening För Barnasjukvård/Stiftelsen Axel Tielmans Minnesfond, Samariten Foundation, Jonasson Center at the Royal Institute of Technology, Sweden, and Initial Training Network Marie Curie Program ‘Growsperm’ (EU-FP7-PEOPLE-2013-ITN 603568). The authors declare no conflicts of interest.

scholarly journals Differential X Chromosome Inactivation Patterns during the Propagation of Human Induced Pluripotent Stem Cells

2016 ◽  
Vol 66 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Tomoko Andoh-noda ◽  
Wado Akamatsu ◽  
Kunio Miyake ◽  
Tetsuro Kobayashi ◽  
Manabu Ohyama ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
X Chromosome ◽  
Pluripotent Stem Cells ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Induced Pluripotent

scholarly journals Human germ cell formation in xenotransplants of induced pluripotent stem cells carrying X chromosome aneuploidies

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Antonia A. Dominguez ◽  
H. Rosaria Chiang ◽  
Meena Sukhwani ◽  
Kyle E. Orwig ◽  
Renee A. Reijo Pera
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
Induced Pluripotent Stem Cells ◽  
X Chromosome ◽  
Pluripotent Stem Cells ◽  
Cell Formation ◽  
Induced Pluripotent ◽  
Germ Cell Formation

scholarly journals X-chromosome inactivation in monkey embryos and pluripotent stem cells

2012 ◽  
Vol 371 (2) ◽  
pp. 146-155 ◽  
Author(s):  
Masahito Tachibana ◽  
Hong Ma ◽  
Michelle L. Sparman ◽  
Hyo-Sang Lee ◽  
Cathy M. Ramsey ◽  
...  
Keyword(s):  
Stem Cells ◽  
X Chromosome ◽  
Pluripotent Stem Cells ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation

scholarly journals X-Chromosome Inactivation during Preimplantation Development and in Pluripotent Stem Cells

2020 ◽  
Vol 160 (6) ◽  
pp. 283-294 ◽  
Author(s):  
Paola Rebuzzini ◽  
Maurizio Zuccotti ◽  
Silvia Garagna
Keyword(s):  
Stem Cells ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Pluripotent Stem Cells ◽  
Mammalian Cells ◽  
Gene Dosage ◽  
X Chromosome Inactivation ◽  
Preimplantation Development ◽  
Chromosome Inactivation ◽  
Transcriptional Gene Silencing

X dosage compensation between XX female and XY male mammalian cells is achieved by a process known as X-chromosome inactivation (XCI). XCI initiates early during preimplantation development in female cells, and it is subsequently stably maintained in somatic cells. However, XCI is a reversible process that occurs in vivo in the inner cell mass of the blastocyst, in primordial germ cells or in spermatids during reprogramming. Erasure of transcriptional gene silencing can occur though a mechanism named X-chromosome reactivation (XCR). XCI and XCR have been substantially deciphered in the mouse, whereas they still remain debated in the human. In this review, we summarized the recent advances in the knowledge of X-linked gene dosage compensation during mouse and human preimplantation development and in pluripotent stem cells.

Transcriptome Characteristics and X-Chromosome Inactivation Status in Cultured Rat Pluripotent Stem Cells

2015 ◽  
Vol 24 (24) ◽  
pp. 2912-2924 ◽  
Author(s):  
Evgeniya A. Vaskova ◽  
Sergey P. Medvedev ◽  
Anastasiya E. Sorokina ◽  
Artem A. Nemudryy ◽  
Evgeniy A. Elisaphenko ◽  
...  
Keyword(s):  
Stem Cells ◽  
X Chromosome ◽  
Pluripotent Stem Cells ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation
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