# Controlled generation of human embryoids using optogenetics

> **NIH NIH R21** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $182,218

## Abstract

Project Summary
Understanding human embryonic development has tremendous impact on improving assisted reproductive
technologies, stem cell-based regenerative therapies, and the prevention of genetic birth defects and
teratogenesis. However, our knowledge about human embryonic development is limited due to drastic species
divergences between humans and other commonly used mammalian models and limited accessibility to
human/non-human primate embryonic tissue samples for research purposes. To overcome these difficulties,
stem cell-based in vitro culture methods that allow spontaneous development of multicellular structures while
simplifying the experimental system and improving accessibility for high-quality live imaging are of tremendous
value. Despite the great promise, the inherent variations of existing culture systems significantly limit their
applications for fundamental mechanistic research and clinical applications. Optogenetic approaches utilize
genetic engineering methods and optical technologies to control biological functions of cells or tissues modified
to express photosensitive proteins. The precise spatiotemporal resolution of optogenetics, coupled with
properly engineered illumination systems, can offer a powerful and versatile solution to improve the
controllability and reproducibility of stem-cell derived human development models.
 Our preliminary studies reveal that exogenous BMP4 stimulation efficiently drives human pluripotent
stem cells (hPSCs) to differentiate into amniotic ectoderm-like cells (AMLCs); and localized exogenous BMP
stimulation to hPSC aggregates generates human embryonic-like structures (or embryoids). In this proposed
research, we will pursue an exploratory, high-risk but high-reward study to demonstrate the integration of
optogenetics and stem cell-derived human embryo models. Specifically, we will derive optogenetic hPSC lines
using an optoBMP system; and examine their intracellular BMP activities and amniotic differentiation potentials
under light exposure. Fully characterized optoBMP-hPSCs will then be utilized to generate, the first of its kind,
optogenetic human embryoid system.
 This research, if successful, will demonstrate, for the first time, the successful generation of human
embryoids with optogenetic perturbation of developmental signals. This is very significant, as there are crucial
issues pervading in existing embryoid culture systems: a lack of reproducibility and controllability and, coupled
to this, our lack of understanding of the processes that guide their development and self-organization.
Incorporating optogenetic tools into existing embryoid cultures will offer the experimenter precise
spatiotemporal control over the key development signals. The improved reproducibility and experimental
consistency will greatly facilitate meaningful mechanistic studies to understand mechanisms that underlie
human embryonic development in normal and pathological situations, and to use them as targets for ...

## Key facts

- **NIH application ID:** 10505751
- **Project number:** 1R21HD109635-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Jianping Fu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $182,218
- **Award type:** 1
- **Project period:** 2022-09-08 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10505751

## Citation

> US National Institutes of Health, RePORTER application 10505751, Controlled generation of human embryoids using optogenetics (1R21HD109635-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10505751. Licensed CC0.

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