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We introduce a generative data augmentation strategy to improve the accuracy of instance segmentation of microscopy data for complex tissue structures. Our pipeline uses regular and conditional generative adversarial networks (GANs) for image-to-image translation to construct synthetic microscopy images along with their corresponding masks to simulate the distribution and shape of the objects and their appearance. The synthetic samples are then used for training an instance segmentation network (for example, StarDist or Cellpose). We show on two single-cell-resolution tissue datasets that our method improves the accuracy of downstream instance segmentation tasks compared with traditional training strategies using either the raw data or basic augmentations. We also compare the quality of the object masks with those generated by a traditional cell population simulation method, finding that our synthesized masks are closer to the ground truth considering Fréchet inception distances., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)