Nuclear and chromatin mechanics in cell fate specification

National Institute Of Diabetes And Digestive And Kidney Diseases

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Abstract

Over the last year we have made significant progress toward all four projects. Project 2) has now been published in Nature Cell Biology (PMID: 39779939) in January 2025, Project 3) has been accepted for publication also at Nature Cell Biology in June 2025. Project 4) has been submitted to Nature in May 2025 and is now out for review there. Significant progress has also been done on Project 1) – we have performed and analyzed H3K9me3 and gammaH2ax Cut&tag experiments as well as DAM ID sequencing, performed epigenetic screen, and finished all mechanistic experiments – we are currently writing up the findings for submission. Thus all 4 projects have been finalized. Publications are as follows: Hervé S, Scelfo A, Bersano-Marchisio G, Grison M, Vaidziulyte K, Deygas M, Nader G, Mace A-S, Gentili M, Williart A, Manel N, Piel M, Miroshnikova YA* (co-last/co-corresponding), Fachinetti*. Chromosome mis-segregation triggers cell cycle arrest through a mechanosensitive nuclear envelope checkpoint (in print at Nat Cell Biol) McCreery K, Stubb A, Stephens R, Cook A, Kruse K, Lackmann J, Niessen CM, Biggs LC, Nykänen S, Zou J, Vuoristo S, Miroshnikova YA (co-last/co-corresponding)*, and Wickström SA*. Mechano-osmotic signals control chromatin state and exit from pluripotency. (accepted Nat Cell Biol; https://www.biorxiv.org/content/10.1101/2024.09.07.611779v1) Kaivola J, Punovuori K, Chastney MR, Miroshnikova YA, Abdo H, Bertillot F, Krautgasser F, Di Franco J, Conway JRW, Follain G, Hagström J, Mäkitie A, Irjala H, Ventelä S, Hamidi H, Scita G, Cerbino R, Wickström SA, and Ivaska J. Restoring mechanophenotype reverts malignant properties of ECM-enriched vocal fold cancer. (https://www.biorxiv.org/content/10.1101/2024.08.22.609159v1) Stephens KR and Miroshnikova YA. Nuclear periphery and its mechanical regulation in cell fate transitions. Curr Opin Struct Biol. 2024. Jun 17:87:102867. Biggs LC and Miroshnikova YA. Nuclear mechanotransduction on skin stem cell fate regulation. Curr. Opin Cell Biol. 2024. Apr: 87:102328