RRC ID 64923
Author Moreau T, Evans AL, Vasquez L, Tijssen MR, Yan Y, Trotter MW, Howard D, Colzani M, Arumugam M, Wu WH, Dalby A, Lampela R, Bouet G, Hobbs CM, Pask DC, Payne H, Ponomaryov T, Brill A, Soranzo N, Ouwehand WH, Pedersen RA, Ghevaert C.
Title Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming.
Journal Nat Commun
Abstract The production of megakaryocytes (MKs)--the precursors of blood platelets--from human pluripotent stem cells (hPSCs) offers exciting clinical opportunities for transfusion medicine. Here we describe an original approach for the large-scale generation of MKs in chemically defined conditions using a forward programming strategy relying on the concurrent exogenous expression of three transcription factors: GATA1, FLI1 and TAL1. The forward programmed MKs proliferate and differentiate in culture for several months with MK purity over 90% reaching up to 2 × 10(5) mature MKs per input hPSC. Functional platelets are generated throughout the culture allowing the prospective collection of several transfusion units from as few as 1 million starting hPSCs. The high cell purity and yield achieved by MK forward programming, combined with efficient cryopreservation and good manufacturing practice (GMP)-compatible culture, make this approach eminently suitable to both in vitro production of platelets for transfusion and basic research in MK and platelet biology.
Volume 7
Pages 11208
Published 2016-4-7
DOI 10.1038/ncomms11208
PII ncomms11208
PMID 27052461
PMC PMC4829662
MeSH Basic Helix-Loop-Helix Transcription Factors / genetics* Basic Helix-Loop-Helix Transcription Factors / metabolism Blood Platelets / cytology Blood Platelets / metabolism Cell Culture Techniques Cell Differentiation Cell Proliferation Cellular Reprogramming* Cryopreservation / methods GATA1 Transcription Factor / genetics* GATA1 Transcription Factor / metabolism Gene Expression Regulation Genes, Reporter Genetic Vectors Green Fluorescent Proteins / genetics Green Fluorescent Proteins / metabolism Humans Lentivirus / genetics Megakaryocytes / cytology* Megakaryocytes / metabolism Microarray Analysis Pluripotent Stem Cells / cytology* Pluripotent Stem Cells / metabolism Proto-Oncogene Protein c-fli-1 / genetics* Proto-Oncogene Protein c-fli-1 / metabolism Proto-Oncogene Proteins / genetics* Proto-Oncogene Proteins / metabolism Signal Transduction T-Cell Acute Lymphocytic Leukemia Protein 1 Transduction, Genetic Transgenes
IF 12.121
Human and Animal Cells 10T1/2(RCB0247)