Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming

Thomas Moreau; Amanda Evans; Louella Vasquez; Marloes Tijssen; Ying Yan; Matthew W.  Trotter; Daniel  Howard; Maria  Colzani; Meera  Arumugam; Wing Han  Wu; Amanda Dalby; Riina  Lampela; Guenaelle  Bouet; Catherine M.  Hobbs; Dean C.  Pask; Holly Payne; Tatyana Ponomaryov; Alexander Brill; Nicole  Soranzo; Willem H.  Ouwehand; Roger A.  Pedersen; Cedric  Ghevaert

doi:10.1038/ncomms11208

Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming

Thomas Moreau, Amanda Evans, Louella Vasquez, Marloes Tijssen, Ying Yan, Matthew W. Trotter, Daniel Howard, Maria Colzani, Meera Arumugam, Wing Han Wu, Amanda Dalby, Riina Lampela, Guenaelle Bouet, Catherine M. Hobbs, Dean C. Pask, Holly Payne, Tatyana Ponomaryov, Alexander Brill, Nicole Soranzo, Willem H. Ouwehand Roger A. Pedersen, Cedric Ghevaert

Cardiovascular Sciences

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Abstract

The production of megakaryocytes (MKs) – the precursors of blood platelets – from human pluripotent stem cells (hPSCs) offers exciting clinical opportunities for transfusion medicine. 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 3 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 2x10⁵ mature MKs per input hPSC. Functional platelets are generated throughout the culture allowing the prospective collection of several transfusion units from as few as one million starting hPSCs. The high cell purity and yield achieved by MK forward programming, combined with efficient cryopreservation and 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.

Original language	English
Article number	11208
Number of pages	16
Journal	Nature Communications
Volume	7
Issue number	1
Early online date	7 Apr 2016
DOIs	https://doi.org/10.1038/ncomms11208
Publication status	Published - 1 Sept 2016

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Moreau, T., Evans, A., Vasquez, L., Tijssen, M., Yan, Y., Trotter, M. W., Howard, D., Colzani, M., Arumugam, M., Wu, W. H., Dalby, A., Lampela, R., Bouet, G., Hobbs, C. M., Pask, D. C., Payne, H., Ponomaryov, T., Brill, A., Soranzo, N., ... Ghevaert, C. (2016). Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming. Nature Communications, 7(1), Article 11208. Advance online publication. https://doi.org/10.1038/ncomms11208

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title = "Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming",

abstract = "The production of megakaryocytes (MKs) – the precursors of blood platelets – from human pluripotent stem cells (hPSCs) offers exciting clinical opportunities for transfusion medicine. 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 3 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 2x105 mature MKs per input hPSC. Functional platelets are generated throughout the culture allowing the prospective collection of several transfusion units from as few as one million starting hPSCs. The high cell purity and yield achieved by MK forward programming, combined with efficient cryopreservation and 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. ",

author = "Thomas Moreau and Amanda Evans and Louella Vasquez and Marloes Tijssen and Ying Yan and Trotter, {Matthew W.} and Daniel Howard and Maria Colzani and Meera Arumugam and Wu, {Wing Han} and Amanda Dalby and Riina Lampela and Guenaelle Bouet and Hobbs, {Catherine M.} and Pask, {Dean C.} and Holly Payne and Tatyana Ponomaryov and Alexander Brill and Nicole Soranzo and Ouwehand, {Willem H.} and Pedersen, {Roger A.} and Cedric Ghevaert",

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Moreau, T, Evans, A, Vasquez, L, Tijssen, M, 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 2016, 'Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming', Nature Communications, vol. 7, no. 1, 11208. https://doi.org/10.1038/ncomms11208

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T1 - Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming

AU - Moreau, Thomas

AU - Evans, Amanda

AU - Vasquez, Louella

AU - Tijssen, Marloes

AU - Yan, Ying

AU - Trotter, Matthew W.

AU - Howard, Daniel

AU - Colzani, Maria

AU - Arumugam, Meera

AU - Wu, Wing Han

AU - Dalby, Amanda

AU - Lampela, Riina

AU - Bouet, Guenaelle

AU - Hobbs, Catherine M.

AU - Pask, Dean C.

AU - Payne, Holly

AU - Ponomaryov, Tatyana

AU - Brill, Alexander

AU - Soranzo, Nicole

AU - Ouwehand, Willem H.

AU - Pedersen, Roger A.

AU - Ghevaert, Cedric

PY - 2016/9/1

Y1 - 2016/9/1

N2 - The production of megakaryocytes (MKs) – the precursors of blood platelets – from human pluripotent stem cells (hPSCs) offers exciting clinical opportunities for transfusion medicine. 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 3 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 2x105 mature MKs per input hPSC. Functional platelets are generated throughout the culture allowing the prospective collection of several transfusion units from as few as one million starting hPSCs. The high cell purity and yield achieved by MK forward programming, combined with efficient cryopreservation and 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.

AB - The production of megakaryocytes (MKs) – the precursors of blood platelets – from human pluripotent stem cells (hPSCs) offers exciting clinical opportunities for transfusion medicine. 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 3 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 2x105 mature MKs per input hPSC. Functional platelets are generated throughout the culture allowing the prospective collection of several transfusion units from as few as one million starting hPSCs. The high cell purity and yield achieved by MK forward programming, combined with efficient cryopreservation and 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.

U2 - 10.1038/ncomms11208

DO - 10.1038/ncomms11208

M3 - Article

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 11208

ER -

Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming

Abstract

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