Article activity feed

  1. Evaluation Summary:

    This is an important and delicately designed study that uses integrated tools to reveal underlying mechanisms of repair of the endometrium at menstruation. It combines single cell sequencing analysis and lineage tracing technologies to strongly prove that repair-specific cells originate from the fibroblast cell clusters and PDGFRα+ endometrial fibroblasts undergo MET and can become incorporated into the luminal epithelium of the post repair tissue.

    (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their name with the authors.)

    Was this evaluation helpful?
  2. Reviewer #1 (Public Review):

    Using a mouse model of menstruation the authors have investigated the contribution of stromal mesenchyme cell populations to the restotation of the luminal epithelium. This work has been performed by combining the strengths of trajectory analysis in single cell RNAseq data with lineage tracking of cells using reporter constructs. This approach is an excellent example of integrating bioinformatic analysis with in vivo modelling to achieve a synergy between the two different types of data. The findings are clear and well presented with careful consideration of confounding issues. The understanding developed of the restoration of the luminal epithelium using this model system helps to define the mechanisms involved in the rapid nature of this event. This understanding is of obvious relevance to a number of related human pathologies. As yet the comparison between the mouse model data and human systems is preliminary.

    Was this evaluation helpful?
  3. Reviewer #2 (Public Review):

    In the manuscript, Kirkwood et al prove that an MET program of fibroblast is responsible for repair of the endometrium at menstruation. The strongest point is that this study combines single cell RNA sequencing and lineage tracing technology to provide strong support to their hypothesis, which will undoutedly help us understand how endometrium repair, not only at menstruation, but also when it is damaged during pathogenic conditions. It may also contribute to the development of novel therapeutic strategies for patients with endometrium-related diseases.

    Was this evaluation helpful?