New article: Transcription Factor Levels after Forward Programming of Human Pluripotent Stem Cells with GATA1, FLI1, and TAL1 Determine Megakaryocyte versus Erythroid Cell Fate Decision

📑 Flow cytometry for near-patient testing in premature neonates reveals variation in platelet function: a novel approach to guide platelet transfusion

Authors:

  • Amanda Dalby
  • Jose Ballester-Beltrán
  • Chiara Lincetto
  • Annett Mueller
  • Nicola Foad
  • Amanda Evans
  • James Baye
  • Ernest Turro
  • Thomas Moreau
  • Marloes R. Tijssen
  • Cedric Ghevaert

Direct Links:

https://dx.doi.org/10.1016%2Fj.stemcr.2018.11.001

Abstract:

The production of blood cells and their precursors from human pluripotent stem cells (hPSCs) in vitro has the potential to make a significant impact upon healthcare provision. We demonstrate that the forward programming of hPSCs through overexpression of GATA1, FLI1, and TAL1 leads to the production of a population of progenitors that can differentiate into megakaryocyte or erythroblasts. Using “rainbow” lentiviral vectors to quantify individual transgene expression in single cells, we demonstrate that the cell fate decision toward an erythroblast or megakaryocyte is dictated by the level of FLI1 expression and is independent of culture conditions. Early FLI1 expression is critical to confer proliferative potential to programmed cells while its subsequent silencing or maintenance dictates an erythroid or megakaryocytic fate, respectively. These committed progenitors subsequently expand and mature into megakaryocytes or erythroblasts in response to thrombopoietin or erythropoietin. Our results reveal molecular mechanisms underlying hPSC forward programming and novel opportunities for application to transfusion medicine.

Other Data:

Published online 2019: . 2018 Dec 11; 11(6): 1462–1478.
  • Received 2018 Mar 23
  • Revised 2018 Nov 1
  • Accepted 2018 Nov 1