Cell cycle–dependent centrosome clustering precedes proplatelet formation

Isabelle C. Becker, Adrian R. Wilkie, Emma Nikols, Estelle Carminita, Harvey G. Roweth, Julia Tilburg, Anthony R. Sciaudone, Leila J. Noetzli, Farheen Fatima, Genevieve Couldwell, Anjana Ray, Alex Mogilner, Kellie R. Machlus, Joseph E. Italiano

Research output: Contribution to journalArticlepeer-review


Platelet-producing megakaryocytes (MKs) primarily reside in the bone marrow, where they duplicate their DNA content with each cell cycle resulting in polyploid cells with an intricate demarcation membrane system. While key elements of the cytoskeletal reorganizations during proplatelet formation have been identified, what initiates the release of platelets into vessel sinusoids remains largely elusive. Using a cell cycle indicator, we observed a unique phenomenon, during which amplified centrosomes in MKs underwent clustering following mitosis, closely followed by proplatelet formation, which exclusively occurred in G1 of interphase. Forced cell cycle arrest in G1 increased proplatelet formation not only in vitro but also in vivo following short-term starvation of mice. We identified that inhibition of the centrosomal protein kinesin family member C1 (KIFC1) impaired clustering and subsequent proplatelet formation, while KIFC1-deficient mice exhibited reduced platelet counts. In summary, we identified KIFC1- and cell cycle–mediated centrosome clustering as an important initiator of proplatelet formation from MKs.

Original languageEnglish (US)
Article numbereadl6153
JournalScience Advances
Issue number25
StatePublished - Jun 2024

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Cell cycle–dependent centrosome clustering precedes proplatelet formation'. Together they form a unique fingerprint.

Cite this