bims-ciryme 2024-01-28 papers

Issue of 2024‒01‒28
two papers selected by
Gabriela Da Silva Xavier, University of Birmingham

Nat Commun. 2024 Jan 20. 15(1): 633

Cell state dependent effects of Bmal1 on melanoma immunity and tumorigenicity.

Xue Zhang, Shishir M Pant, Cecily C Ritch, Hsin-Yao Tang, Hongguang Shao, Harsh Dweep, Yao-Yu Gong, Rebekah Brooks, Patricia Brafford, Adam J Wolpaw, Yool Lee, Ashani Weeraratna, Amita Sehgal, Meenhard Herlyn, Andrew Kossenkov, David Speicher, Peter K Sorger, Sandro Santagata, Chi V Dang.

The circadian clock regulator Bmal1 modulates tumorigenesis, but its reported effects are inconsistent. Here, we show that Bmal1 has a context-dependent role in mouse melanoma tumor growth. Loss of Bmal1 in YUMM2.1 or B16-F10 melanoma cells eliminates clock function and diminishes hypoxic gene expression and tumorigenesis, which could be rescued by ectopic expression of HIF1α in YUMM2.1 cells. By contrast, over-expressed wild-type or a transcriptionally inactive mutant Bmal1 non-canonically sequester myosin heavy chain 9 (Myh9) to increase MRTF-SRF activity and AP-1 transcriptional signature, and shift YUMM2.1 cells from a Sox10high to a Sox9high immune resistant, mesenchymal cell state that is found in human melanomas. Our work describes a link between Bmal1, Myh9, mouse melanoma cell plasticity, and tumor immunity. This connection may underlie cancer therapeutic resistance and underpin the link between the circadian clock, MRTF-SRF and the cytoskeleton.

DOI: https://doi.org/10.1038/s41467-024-44778-2

Curr Opin Genet Dev. 2024 Jan 23. pii: S0959-437X(24)00001-7. [Epub ahead of print]84 102152

Emergence of the circadian clock oscillation during the developmental process in mammals.

Kazuhiro Yagita.

The circadian clocks are cell-autonomous intrinsic oscillators existing throughout the body to coordinate intracellular and intercellular functions of each organ or tissue. The circadian clock oscillation gradually emerges during mid-to-late gestation in the mammalian developmental process. Recently, it has been revealed that the in vitro differentiation of mouse ES cells recapitulates the circadian clock development. Moreover, reprogramming of the cells results in the redisappearance of the clock, indicating that circadian clocks are tightly coupled with cellular differentiation. Interestingly, before the circadian clock develops, the embryo is governed under ultradian rhythms driven by the segmentation clock. This short review explores these observations, discussing the significance of the emergence of circadian clock oscillation during the mammalian developmental process.

DOI: https://doi.org/10.1016/j.gde.2024.102152