# Origin and Life Cycle of the Uterine Natural Killer Cell: Novel Insights from Human Uterus Transplantation

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $367,004

## Abstract

Uterine natural killer cells (uNK) are an innate lymphoid population that are critical
determinants of pregnancy success. Despite extensive research, fundamental
knowledge gaps remain regarding the origin and composition of uNK cells in the
endometrium and the molecular mechanisms driving uNK differentiation. These gaps
result in part from our inability to address these essential questions in a human model.
We have combined cutting-edge next generation sequencing methodologies with access
to human uterus transplant recipients to answer questions about uNK trafficking, function
and differentiation that will advance our understanding of pregnancy and its
complicatons. The central premise of this proposal is that placentation, and therefore
pregnancy fate, is pre-determined in part by the differentiation of uNK cells which
populate the maternal-fetal interface prior to embryo implantation. Herein, we build upon
this premise and test the following hypotheses: 1) uNKs which derive from peripheral
and tissue-resident progenitor populations possess distinct transcriptional signatures,
and 2) the Nuclear Factor of Activated T cells (NFAT) is a key transcription factor that
promotes the differentiation of immature endometrial NK cells into mature decidual NK
cells. Uterus transplant recipients provide an opportunity to answer foundational
questions about uNK cell biology in human beings and will yield new insights into the
pathogenesis of pregnancy complications.

## Key facts

- **NIH application ID:** 10238074
- **Project number:** 5R01AI145905-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Kathleen Elise O'Neill
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $367,004
- **Award type:** 5
- **Project period:** 2019-09-10 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10238074

## Citation

> US National Institutes of Health, RePORTER application 10238074, Origin and Life Cycle of the Uterine Natural Killer Cell: Novel Insights from Human Uterus Transplantation (5R01AI145905-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10238074. Licensed CC0.

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