Mapping the biogenesis of forward programmed megakaryocytes from induced pluripotent stem cells
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Authors
Publication Date
2022-02-18Journal Title
Science Advances
ISSN
2375-2548
Publisher
American Association for the Advancement of Science
Volume
8
Issue
7
Language
eng
Type
Article
This Version
VoR
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Ghevaert, C. (2022). Mapping the biogenesis of forward programmed megakaryocytes from induced pluripotent stem cells. Science Advances, 8 (7) https://doi.org/10.1126/sciadv.abj8618
Abstract
Platelet deficiency, known as thrombocytopenia, can cause haemorrhage and is treated with
platelet transfusions. We developed a system for the production of platelet precursor cells,
megakaryocytes, from pluripotent stem cells. These cultures can be maintained for >100 days,
implying culture renewal by megakaryocyte progenitors (MKPs). However, it is unclear
whether the MKP state in vitro mirrors the state in vivo, and MKPs cannot be purified using
conventional surface markers. We performed single cell RNA sequencing throughout in vitro
differentiation and mapped each state to its equivalent in vivo. This enabled the identification
of 5 surface markers which reproducibly purify MKPs, allowing us an insight into their
transcriptional and epigenetic profiles. Finally, we performed culture optimisation, increasing
MKP production. Altogether, this study has mapped parallels between the MKP states in vivo
and in vitro and allowed the purification of MKPs, accelerating the progress of in vitro-derived
transfusion products towards the clinic.
Sponsorship
Wellcome Trust (203151/A/16/Z)
Wellcome Trust (203151/Z/16/Z)
Wellcome Trust (102160/B/13/Z)
Medical Research Council (MR/R015724/1)
British Heart Foundation (None)
Medical Research Council (MC_PC_17230)
Identifiers
35171685, PMC8849335
External DOI: https://doi.org/10.1126/sciadv.abj8618
This record's URL: https://www.repository.cam.ac.uk/handle/1810/335235
Rights
Attribution-NonCommercial 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc/4.0/
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