Induced pluripotent reprogramming from promiscuous human sternness-related factors

Timothy J Nelson, Almudena Martinez-Fernandez, Satsuki Yamada, Amber A. Mael, Andre Terzic, Yasuhiro H Ikeda

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Ectopic expression of pluripotency gene sets provokes nuclear reprogramming in permissive somatic tissue environments, generating nduced pluripotent stem (iPS) cells. The evolutionary conserved function of sternness orthologs was tested here through interspecies transduction. A spectrum of human immunodeficiency virus (HIV)-based lentiviral vectors was designed, and point mutations in the HIV-1 capsid region were identified for efficient infectivity and expanded transspecies tropism. Human pluripotent gene sequences, OCT3/4, SOX2, KLF4, and c-MYC, packaged into engineered lentiviral expression vectors achieved consistent expression in nonhuman fibroblasts. Despite variation in primary amino acid sequence between species, introduction of human pluripotent genes produced cell lines with embryonic stem cell-like morphology. Transduced fibroblasts differentiated in vitro into all three germ layers according to gastrulation gene expression profiles, and formed in vivo teratoma with multilineage potential. Reprogrammed progeny incorporated into nonhuman morula to produce blastomeres capable of developing into chimeric embryos with competent organogenesis. This model system establishes a prototypic approach to examine consequences of human sternness factors-induced reprogramming in the context of normal embryonic development by exploiting nonhuman early-stage embryos. Thus, ectopic xenotransduction across species unmasks the promiscuous nature of sternness induction, suggesting evolutionary selection of core processes for somatic tissue reprogramming.

Original languageEnglish (US)
Pages (from-to)118-126
Number of pages9
JournalClinical and Translational Science
Volume2
Issue number2
DOIs
StatePublished - 2009

Fingerprint

Genes
Fibroblasts
Stem cells
Viruses
Embryonic Structures
Tissue
Morula
Germ Layers
Blastomeres
Pluripotent Stem Cells
Gastrulation
Tropism
Organogenesis
Capsid
Teratoma
Embryonic Stem Cells
Human engineering
Transcriptome
Point Mutation
Gene expression

Keywords

  • c-MYC
  • Chimera
  • HIV
  • iPS
  • KLF4
  • Lentiviral
  • OCT3/4
  • Ortholog
  • SOX2

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Induced pluripotent reprogramming from promiscuous human sternness-related factors. / Nelson, Timothy J; Martinez-Fernandez, Almudena; Yamada, Satsuki; Mael, Amber A.; Terzic, Andre; Ikeda, Yasuhiro H.

In: Clinical and Translational Science, Vol. 2, No. 2, 2009, p. 118-126.

Research output: Contribution to journalArticle

Nelson, Timothy J ; Martinez-Fernandez, Almudena ; Yamada, Satsuki ; Mael, Amber A. ; Terzic, Andre ; Ikeda, Yasuhiro H. / Induced pluripotent reprogramming from promiscuous human sternness-related factors. In: Clinical and Translational Science. 2009 ; Vol. 2, No. 2. pp. 118-126.
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