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We thought there wasn't much new to learn about the cell cycle. Turns out we were wrong! Our paper (out today @Nature) identifies a novel alternative cell cycle that regulates differentiation, not cell division. tinyurl.com/4a6yeuke. 1/10
Semil Choksi
112 posts
Semil Choksi
@semilc
Scientist @UCSF studying cell fate specification, transcription factors and motile cilia. Food and dog take up the rest of my time.
San Francisco, CA
Joined April 2009
- How do stem cells generate the multiciliated and secretory cells of the airway epithelium that protect the lungs from pathogens and particulates in the air? Get ready for a deep dive into airway stem cell fate decisions in our new preprint out now! biorxiv.org/content/10.110…
00:00 - Replying to @semilcCheck out beautiful recent work from the Meunier lab exploring the role of cyclin O (a non-canonical cyclin) in this alternative cell cycle: (tinyurl.com/nz9fnc7k, tinyurl.com/uaveypwc). 8/10
- Replying to @semilcWith the multiciliation cycle, there are now at least four major cell cycle variants. Maybe the cell cycle is redeployed in other contexts to regulate differentiation as well? Check out the paper for more details and data: tinyurl.com/4a6yeuke. 9/10
- Replying to @semilcThe multiciliation cycle is a terminal cycle that amplifies centrioles while repressing DNA replication. This is akin to cell cycle variants like the endocycle in which DNA replication is enhanced or the meiotic cycle which has an extra round of cytokinesis. 7/10
- Replying to @semilcWe identify cyclin D1-CDK4/6 as a novel regulator of entry into the multiciliation cycle and differentiation initiation. We also show that E2F7, a repressor, prevents DNA replication in differentiating multiciliated cells. Mice lacking E2F7 show defects in multiciliation! 6/10
GIF - Replying to @semilcMany labs have shown that individual mitotic regulators are involved in multiciliated cell differentiation. We show that these individual regulators are organized into a cell cycle-like network that coordinates multiciliated cell differentiation, not cell division. 5/10
00:00 - Replying to @semilcA great team made this project really fun to work on – especially Lauren Byrnes and @ReiterLab. Big thanks to @KonjikusicMia, Benedict Tsai, Rachel Deleon and collaborators Quanlong Lu and Chris Westlake! 10/10
- Replying to @semilcWe found that across the stages of differentiation, multiciliated cells express regulators of the mitotic cell cycle – CDKs and their paired cyclins. But these cells are post-mitotic. Why do terminally differentiated cells express regulators of cell division? 4/10
GIF - Replying to @semilcMost cells can only make 2-4 centrioles. Multiciliated cells generate hundreds (!) of centrioles, to make the necessary cilia at the cell surface. How do these cells make 50x the normal number of centrioles?!? 3/10
- Replying to @semilcWe call this new cell cycle variant the “multiciliation cycle”, for the specialized multiciliated cells that it generates. Multiciliated cells form hundreds of cilia which beat to move fluids, for instance to clear mucus and pathogens (like SARS-CoV-2) from the airways. 2/10
- Replying to @semilcHuge thanks to: Jeremy (@reiterlab) for his fantastic mentorship throughout this project. First author Lauren Byrnes for making this such a fun and exciting collaboration. And Rachel Deleon for incredible technical assistance.
- Replying to @semilcSo these two opposing transcription factors are regulating the same gene expression program through the same regulatory regions, but in two different cell lineages, all regulated by Notch signaling!
- Replying to @semilcMuch more in the paper including scRNA-seq of knockouts of other multiciliated cell fate regulators, GMNC and MCIDAS, and a deeper exploration of the earliest multiciliated and secretory cell precursor gene expression programs. Send us feedback – we’d love to get your input!