Constraints on Human CD34+ Cell Fate due to Lentiviral Vectors Can Be Relieved by Valproic Acid

Hum Gene Ther. 2019 Aug;30(8):1023-1034. doi: 10.1089/hum.2019.009. Epub 2019 May 15.


The initial stages following the in vitro cytokine stimulation of human cord blood CD34+ cells overlap with the period when lentiviral gene transfer is typically performed. Single-cell transcriptional profiling and time-lapse microscopy were used to investigate how the vector-cell crosstalk impacts on the fate decision process. The single-cell transcription profiles were analyzed using a new algorithm, and it is shown that lentiviral transduction during the early stages of stimulation modifies the dynamics of the fate choice process of the CD34+ cells. The cells transduced with a lentiviral vector are biased toward the common myeloid progenitor lineage. Valproic acid, a histone deacetylase inhibitor known to increase the grafting potential of the CD34+ cells, improves the transduction efficiency to almost 100%. The cells transduced in the presence of valproic acid can subsequently undergo normal fate commitment. The higher gene transfer efficiency did not alter the genomic integration profile of the vector. These observations open the way to substantially improving lentiviral gene transfer protocols.

Keywords: CALISTA; fate commitment; hematopoietic stem cell; single-cell; transduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Cell Differentiation / drug effects
  • Fetal Blood / cytology
  • Gene Expression
  • Gene Transfer Techniques
  • Genetic Vectors / genetics*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects*
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Lentivirus / genetics*
  • Phenotype
  • Transduction, Genetic*
  • Transgenes
  • Valproic Acid / pharmacology*
  • Virus Integration


  • Biomarkers
  • Valproic Acid