Donor Dependent Variations in Hematopoietic Differentiation among Embryonic and Induced Pluripotent Stem Cell Lines

PLoS One. 2016 Mar 3;11(3):e0149291. doi: 10.1371/journal.pone.0149291. eCollection 2016.

Abstract

Hematopoiesis generated from human embryonic stem cells (ES) and induced pluripotent stem cells (iPS) are unprecedented resources for cell therapy. We compared hematopoietic differentiation potentials from ES and iPS cell lines originated from various donors and derived them using integrative and non-integrative vectors. Significant differences in differentiation toward hematopoietic lineage were observed among ES and iPS. The ability of engraftment of iPS or ES-derived cells in NOG mice varied among the lines with low levels of chimerism. iPS generated from ES cell-derived mesenchymal stem cells (MSC) reproduce a similar hematopoietic outcome compared to their parental ES cell line. We were not able to identify any specific hematopoietic transcription factors that allow to distinguish between good versus poor hematopoiesis in undifferentiated ES or iPS cell lines. There is a relatively unpredictable variation in hematopoietic differentiation between ES and iPS cell lines that could not be predicted based on phenotype or gene expression of the undifferentiated cells. These results demonstrate the influence of genetic background in variation of hematopoietic potential rather than the reprogramming process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cell Differentiation
  • Cell Line
  • Cell Lineage / genetics
  • Cellular Reprogramming / genetics*
  • Chimerism
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism
  • Embryonic Stem Cells / transplantation
  • Gene Expression
  • Genetic Heterogeneity*
  • Genetic Vectors
  • Graft Survival*
  • Hematopoiesis / genetics*
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism
  • Induced Pluripotent Stem Cells / transplantation
  • Lentivirus / genetics
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Retroviridae / genetics
  • Tissue Donors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transplantation, Heterologous

Substances

  • Biomarkers
  • Transcription Factors

Grant support

INSERM, Univ. Paris Sud, Paris Saclay. Pôle de compétitivité MEDICEN (IngeCELL project), DIM Stem Pôle Ile de France. Vaincre le Cancer-NRB and ANR « Programme Investissements Avenir » INGESTEM (ANR-11-INBS-0009). Authors Aurélie Daury and Corinne Rocher are employed by Sanofi. Sanofi provided support in the form of salaries for authors Aurélie Daury and Corinne Rocher, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.