Mapping the biogenesis of forward programmed megakaryocytes from induced pluripotent stem cells.
American Association for the Advancement of Science (AAAS)
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Lawrence, M., Shahsavari, A., Borneloev, S., Moreau, T., McDonald, R., Vallance, T., Kania, K., et al. (2022). Mapping the biogenesis of forward programmed megakaryocytes from induced pluripotent stem cells.. Sci Adv https://doi.org/10.1126/sciadv.abj8618
Platelet deficiency, known as thrombocytopenia, can cause hemorrhage 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 five surface markers that reproducibly purify MKPs, allowing us insight into their transcriptional and epigenetic profiles. Last, we performed culture optimization, increasing MKP production. Together, 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 toward the clinic.
Wellcome Trust (203151/A/16/Z)
Wellcome Trust (203151/Z/16/Z)
Wellcome Trust (102160/B/13/Z)
Medical Research Council (MR/R015724/1)
External DOI: https://doi.org/10.1126/sciadv.abj8618
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336225
Attribution-NonCommercial 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc/4.0/