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Mapping the biogenesis of forward programmed megakaryocytes from induced pluripotent stem cells
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 renew...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8849335/ https://www.ncbi.nlm.nih.gov/pubmed/35171685 http://dx.doi.org/10.1126/sciadv.abj8618 |
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author | Lawrence, Moyra Shahsavari, Arash Bornelöv, Susanne Moreau, Thomas McDonald, Rebecca Vallance, Thomas M. Kania, Katarzyna Paramor, Maike Baye, James Perrin, Marion Steindel, Maike Jimenez-Gomez, Paula Penfold, Christopher Mohorianu, Irina Ghevaert, Cedric |
author_facet | Lawrence, Moyra Shahsavari, Arash Bornelöv, Susanne Moreau, Thomas McDonald, Rebecca Vallance, Thomas M. Kania, Katarzyna Paramor, Maike Baye, James Perrin, Marion Steindel, Maike Jimenez-Gomez, Paula Penfold, Christopher Mohorianu, Irina Ghevaert, Cedric |
author_sort | Lawrence, Moyra |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8849335 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-88493352022-03-04 Mapping the biogenesis of forward programmed megakaryocytes from induced pluripotent stem cells Lawrence, Moyra Shahsavari, Arash Bornelöv, Susanne Moreau, Thomas McDonald, Rebecca Vallance, Thomas M. Kania, Katarzyna Paramor, Maike Baye, James Perrin, Marion Steindel, Maike Jimenez-Gomez, Paula Penfold, Christopher Mohorianu, Irina Ghevaert, Cedric Sci Adv Biomedicine and Life Sciences 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. American Association for the Advancement of Science 2022-02-16 /pmc/articles/PMC8849335/ /pubmed/35171685 http://dx.doi.org/10.1126/sciadv.abj8618 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Lawrence, Moyra Shahsavari, Arash Bornelöv, Susanne Moreau, Thomas McDonald, Rebecca Vallance, Thomas M. Kania, Katarzyna Paramor, Maike Baye, James Perrin, Marion Steindel, Maike Jimenez-Gomez, Paula Penfold, Christopher Mohorianu, Irina Ghevaert, Cedric Mapping the biogenesis of forward programmed megakaryocytes from induced pluripotent stem cells |
title | Mapping the biogenesis of forward programmed megakaryocytes from induced pluripotent stem cells |
title_full | Mapping the biogenesis of forward programmed megakaryocytes from induced pluripotent stem cells |
title_fullStr | Mapping the biogenesis of forward programmed megakaryocytes from induced pluripotent stem cells |
title_full_unstemmed | Mapping the biogenesis of forward programmed megakaryocytes from induced pluripotent stem cells |
title_short | Mapping the biogenesis of forward programmed megakaryocytes from induced pluripotent stem cells |
title_sort | mapping the biogenesis of forward programmed megakaryocytes from induced pluripotent stem cells |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8849335/ https://www.ncbi.nlm.nih.gov/pubmed/35171685 http://dx.doi.org/10.1126/sciadv.abj8618 |
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