Generation of human iPSCs from an essential thrombocythemia patient carrying a V501L mutation in the MPL gene

Senquan Liu; Zhaohui Ye; Yongxing Gao; Chaoxia He; Donna W Williams; Alison Moliterno; Jerry Spivak; He Huang; Linzhao Cheng

doi:10.1016/j.scr.2016.12.012

Generation of human iPSCs from an essential thrombocythemia patient carrying a V501L mutation in the MPL gene

Stem Cell Res. 2017 Jan:18:57-59. doi: 10.1016/j.scr.2016.12.012. Epub 2016 Dec 11.

Authors

Senquan Liu¹, Zhaohui Ye², Yongxing Gao², Chaoxia He², Donna W Williams³, Alison Moliterno³, Jerry Spivak³, He Huang⁴, Linzhao Cheng²

Affiliations

¹ Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, PR China; Division of Hematology, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Stem Cell Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
² Division of Hematology, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Stem Cell Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
³ Division of Hematology, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁴ Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, PR China. Electronic address: huanghe@zju.edu.cn.

PMID: 28395806
DOI: 10.1016/j.scr.2016.12.012

Abstract

Activating point mutations in the MPL gene encoding the thrombopoietin receptor are found in 3%-10% of essential thrombocythemia (ET) and myelofibrosis patients. Here, we report the derivation of induced pluripotent stem cells (iPSCs) from an ET patient with a heterozygous MPL V501L mutation. Peripheral blood CD34⁺ progenitor cells were reprogrammed by transient plasmid expression of OCT4, SOX2, KLF4, c-MYC plus BCL2L1 (BCL-xL) genes. The derived line M494 carries a MPL V501L mutation, displays typical iPSC morphology and characteristics, are pluripotent and karyotypically normal. Upon differentiation, the iPSCs are able to differentiate into cells derived from three germ layers.

MeSH terms

Antigens, CD34 / metabolism
Base Sequence
Cell Differentiation
Cell Line
Cellular Reprogramming*
DNA Mutational Analysis
Embryoid Bodies / metabolism
Embryoid Bodies / pathology
Female
Genotype
Heterozygote
Humans
Induced Pluripotent Stem Cells / cytology*
Induced Pluripotent Stem Cells / metabolism
Induced Pluripotent Stem Cells / transplantation
Karyotype
Kruppel-Like Factor 4
Microscopy, Fluorescence
Polymorphism, Single Nucleotide
Receptors, Thrombopoietin / genetics*
Stem Cells / cytology
Stem Cells / metabolism
Teratoma / metabolism
Teratoma / pathology
Thrombocythemia, Essential / genetics
Thrombocythemia, Essential / metabolism
Thrombocythemia, Essential / pathology*
Transcription Factors / genetics
Transcription Factors / metabolism

Substances

Antigens, CD34
KLF4 protein, human
Kruppel-Like Factor 4
Receptors, Thrombopoietin
Transcription Factors
MPL protein, human