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Updated: Jun 10, 2026

Isolation of Mouse Megakaryocyte Progenitors
Published on: May 20, 2021
Polyploid megakaryocytes can complete cytokinesis
Younes Leysi-Derilou1, Amélie Robert, Carl Duchesne
1Department of Chemical Engineering, Laval University, Québec, QC, Canada.
Abstract:
Megakaryocytes (MK) undergo polyploidization through endomitosis, a mitotic process that ends prematurely due to aborted cytokinesis. To better understand this and other events associated with MK differentiation, we performed long-term and large-field live cell imaging of human MKs derived in cord blood (CB) and bone marrow (BM) CD34(+) cell cultures. Polyploid level of imaged cells was evaluated using three complementary approaches; cell history, cell size and ploidy correlation and nuclei staining. This system and strategy enabled the direct observation of the development of a large number of MKs (n=4865) and to quantify their fates. The most significant finding of this study is that a considerable proportion of polyploid MKs could complete cytokinesis. This unexpected process gave rise to polyploid daughter cell(s) with normal fates and contributed significantly to the expansion of polyploid MKs. Further analyses revealed that the proliferation rate amongst polyploid MKs was inversely correlated to their ploidy level, and that this phenomenon was much more frequent in CB- than BM-derived MKs. Accordingly, endomitosis was identified as the dominant fate of polyploid BM-MKs, while this was less accentuated for polyploid CB-MKs. These findings explain partially why CB-derived MKs remain in lower ploidy class. In conclusion, this study demonstrates that the development of polyploid MK results from the failure and/or success of cytokinesis and brings a new paradigm to the field of megakaryopoiesis.
Insights
Polyploid megakaryocytes (MKs) can complete cell division, producing more polyploid cells. This successful cytokinesis, rather than just failed division, is key to megakaryocyte development and expansion.
Area of Science:
- Cell Biology
- Hematopoiesis
- Molecular Biology
Background:
- Megakaryocytes (MKs) are essential for platelet production and undergo endomitosis, a process involving DNA replication without cell division.
- Endomitosis typically results in polyploid MKs due to failed cytokinesis, but the precise mechanisms and outcomes are not fully understood.
Purpose of the Study:
- To investigate the dynamics of polyploid megakaryocyte development and cytokinesis using live cell imaging.
- To quantify the contribution of successful and failed cytokinesis to polyploid MK expansion.
- To compare MK differentiation from cord blood (CB) and bone marrow (BM) sources.
Main Methods:
- Long-term, large-field live cell imaging of human MKs derived from CD34+ cells in CB and BM cultures.
- Evaluation of polyploid levels using cell history, cell size/ploidy correlation, and nuclei staining.
- Direct observation and quantification of MK fates (n=4865).
Main Results:
- A significant proportion of polyploid MKs successfully completed cytokinesis, generating polyploid daughter cells.
- Successful cytokinesis contributed substantially to the expansion of the polyploid MK pool.
- Proliferation rate in polyploid MKs inversely correlated with ploidy level, more pronounced in CB-derived MKs.
- Endomitosis was the dominant fate in BM-MKs, less so in CB-MKs, explaining lower ploidy in CB-derived MKs.
Conclusions:
- Megakaryocyte polyploidization results from both the failure and success of cytokinesis.
- Successful cytokinesis represents a novel mechanism for polyploid MK expansion, challenging previous paradigms.
- Differences in cytokinesis success contribute to variations in ploidy levels between CB- and BM-derived MKs.
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