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A major challenge in studying megakaryocyte development, and the diseases that arise from their dysfunction, is the identification, classification, and enrichment of megakaryocyte progenitor cells that are produced during hematopoiesis. Here, we present a high throughput strategy for identifying and isolating megakaryocytes and their progenitor cells from a heterogeneous population of bone marrow samples. Specifically, we couple thrombopoietin (TPO) induction, image flow cytometry, and principal component analysis (PCA) to identify and enrich for megakaryocyte progenitor cells that are capable of self-renewal and directly differentiating into mature megakaryocytes. This enrichment strategy distinguishes megakaryocyte progenitors from other lineage-committed cells in a high throughput manner. Furthermore, by using image flow cytometry with PCA, we have identified a combination of markers and characteristics that can be used to isolate megakaryocyte progenitor cells using standard flow cytometry methods. Altogether, these techniques enable the high throughput enrichment and isolation of cells in the megakaryocyte lineage and have the potential to enable rapid disease identification and diagnoses ahead of severe disease progression.<\/jats:p>","DOI":"10.1038\/s41598-021-87681-2","type":"journal-article","created":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T06:18:05Z","timestamp":1618467485000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["High-throughput enrichment and isolation of megakaryocyte progenitor cells from the mouse bone marrow"],"prefix":"10.1038","volume":"11","author":[{"given":"Lucas M.","family":"Bush","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connor P.","family":"Healy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Marvin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara L.","family":"Deans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,15]]},"reference":[{"key":"87681_CR1","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1182\/blood-2013-03-492801","volume":"122","author":"B Laffont","year":"2013","unstructured":"Laffont, B. et al. Activated platelets can deliver mRNA regulatory Ago2*microRNA complexes to endothelial cells via microparticles. Blood 122, 253\u2013261. https:\/\/doi.org\/10.1182\/blood-2013-03-492801 (2013).","journal-title":"Blood"},{"key":"87681_CR2","doi-asserted-by":"publisher","first-page":"101695","DOI":"10.1016\/j.pneurobio.2019.101695","volume":"183","author":"O Leiter","year":"2019","unstructured":"Leiter, O. & Walker, T. L. Platelets: The missing link between the blood and brain?. Prog. Neurobiol. 183, 101695. https:\/\/doi.org\/10.1016\/j.pneurobio.2019.101695 (2019).","journal-title":"Prog. Neurobiol."},{"key":"87681_CR3","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1002\/sctm.16-0490","volume":"6","author":"H Nishikii","year":"2017","unstructured":"Nishikii, H., Kurita, N. & Chiba, S. The road map for megakaryopoietic lineage from hematopoietic stem\/progenitor cells. Stem Cells Transl. 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