Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Physician-Scientist Development
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • In-Press Preview
    • Resource and Technical Advances
    • Clinical Research and Public Health
    • Research Letters
    • Editorials
    • Perspectives
    • Physician-Scientist Development
    • Reviews
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Resource and Technical Advances
  • Clinical Research and Public Health
  • Research Letters
  • Editorials
  • Perspectives
  • Physician-Scientist Development
  • Reviews
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
Single-cell mapping of human endometrium and decidua reveals epithelial and stromal contributions to fertility
Gregory W. Burns, Emmanuel N. Paul, Manisha Persaud, Qingshi Zhao, Rong Li, Kristin Blackledge, Jessica Garcia de Paredes, Pratibha Shukla, Ripla Arora, Anat Chemerinski, Nataki C. Douglas
Gregory W. Burns, Emmanuel N. Paul, Manisha Persaud, Qingshi Zhao, Rong Li, Kristin Blackledge, Jessica Garcia de Paredes, Pratibha Shukla, Ripla Arora, Anat Chemerinski, Nataki C. Douglas
View: Text | PDF
Research Article Cell biology Reproductive biology

Single-cell mapping of human endometrium and decidua reveals epithelial and stromal contributions to fertility

  • Text
  • PDF
Abstract

The human endometrium undergoes dynamic changes across the menstrual cycle to establish a receptive state for embryo implantation. Using bulk and single-cell RNA-Seq, we characterized gene expression dynamics in the cycling endometrium and the decidua from early pregnancy. We demonstrated that during the mid-secretory phase — the period encompassing the window of implantation — secretory glandular epithelial cells undergo notable transcriptional changes and alterations in cell-cell communication. Through comprehensive analyses, we identified the glandular epithelium receptivity module (GERM) signature, comprising 556 genes associated with endometrial receptivity. This GERM signature was consistently perturbed across datasets of endometrial samples from women with impaired fertility, validating its relevance as a marker of receptivity. In addition to epithelial changes, we observed shifts in stromal cell populations, notably involving decidual and senescent subsets, which also play key roles in modulating implantation. Together, these findings provide a high-resolution transcriptomic atlas of the receptive and early pregnant endometrium and shed light on key molecular pathways underlying successful implantation.

Authors

Gregory W. Burns, Emmanuel N. Paul, Manisha Persaud, Qingshi Zhao, Rong Li, Kristin Blackledge, Jessica Garcia de Paredes, Pratibha Shukla, Ripla Arora, Anat Chemerinski, Nataki C. Douglas

×

Figure 1

Identification of the transcriptomic profile and dynamic cell populations in the endometrium over time.

Options: View larger image (or click on image) Download as PowerPoint
Identification of the transcriptomic profile and dynamic cell population...
(A) Summary of sample collection. (B) UMAP visualization of mRNA-Seq from proliferative (n = 6), early (n = 10), mid- (n = 7), and late (n = 3) secretory phase human endometrial samples. The color of each symbol indicates menstrual cycle stage; the shape denotes BMI category (kg/m2): normal (18–24.9), overweight (25–29.9), and obese (≥ 30). (C) Euler plot of the DEGs from proliferative versus mid-secretory, early versus mid-secretory, and late versus mid-secretory phase endometrial samples. (D) UMAP visualization of 171,261 isolated cells from human endometrial samples (n = 14). Each cluster (n = 17) represents a cell population with a similar transcriptomic profile. (E) Dot plot for cluster identification using specific markers for cell types from the endometrium. Average gene expression and percentage of cells expressing the specific gene in each cell cluster are shown by the color intensity and the diameter of the dot, respectively. (F) Stacked bar plot showing the proportion of cells in each cluster by stage.

Copyright © 2026 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts