Downregulation of ROCK improves ploidy but increases genomic instability in Fanca^−/− MKs. Ploidy analysis of CD41⁺ cells after 3-day culture with TPO, with or without the ROCK inhibitor Y27632: (A) representative flow cytometry histograms; (B) mean ploidy of all CD41⁺ cells; and (C) mean ploidy of CD41⁺ cells with ≥8N (n = 4 per group of WT; n = 5 per group of Fanca^−/−, *P < .05, Student t test). (D) Frequency of chromosomal aberrations scored in a minimum of 30 metaphases per point (n = 3 per group, *P < .05, Student t test), with or without ROCK inhibitor. (E) Number of colonies obtained at day 6 of MegaCult-C under the same conditions described above (n = 5 per group, *P < .05, Student t test). Means ± SEM are shown. (F) Proposed model for development of thrombocytopenia in Fanca^−/− mice. See discussion for details.