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

Olivier Féraud; Yannick Valogne; Michael W Melkus; Yanyan Zhang; Noufissa Oudrhiri; Rima Haddad; Aurélie Daury; Corinne Rocher; Aniya Larbi; Philippe Duquesnoy; Dominique Divers; Emilie Gobbo; Philippe Brunet de la Grange; Fawzia Louache; Annelise Bennaceur-Griscelli; Maria Teresa Mitjavila-Garcia

doi:10.1371/journal.pone.0149291

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.

Authors

Olivier Féraud^{1

2}, Yannick Valogne¹, Michael W Melkus^{1

3}, Yanyan Zhang⁴, Noufissa Oudrhiri^{1

2

5}, Rima Haddad^{1

6}, Aurélie Daury⁷, Corinne Rocher⁷, Aniya Larbi¹, Philippe Duquesnoy⁸, Dominique Divers^{1

2}, Emilie Gobbo^{1

2}, Philippe Brunet de la Grange⁹, Fawzia Louache⁴, Annelise Bennaceur-Griscelli^{1

2

5

6

10}, Maria Teresa Mitjavila-Garcia¹

Affiliations

¹ INSERM UMR935, SFR André Lwoff, University Paris Sud, Paul Brousse Hospital, Villejuif, France.
² Human Embryonic Stem Cell Core Facility, ESTeam Paris Sud, Villejuif, France.
³ Department of Pediatrics and Center for Tropical Medicine and Infectious Diseases, Texas Tech University Health Science Center, Amarillo, TX, United States of America.
⁴ INSERM UMR U1170, Institut Gustave Roussy, Villejuif, France.
⁵ AP-HP, Department of Hematology, University Hospitals Paris Sud, Paul Brousse Hospital, Villejuif, France.
⁶ Faculty of Medicine, Kremlin-Bicêtre, University, Paris Sud, Paris Saclay, France.
⁷ Sanofi, Department of Regenerative Medicine, Global Biotherapeutics, Vitry-sur-Seine, France.
⁸ INSERM/UMR S933, University Pierre and Marie Curie-Paris 6, Paris, France.
⁹ INSERM UMR 972, SFR André Lwoff, Paul Brousse, Hospital, Villejuif, University Paris Sud, Paris Saclay, France.
¹⁰ National Infrastructure INGESTEM, University Paris Sud, Inserm, Paris, France.

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

Grants and funding

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.