# Single Cell Tracking of 3D Epigenetic Landscape Evolution During Embryonic Development

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $679,397

## Abstract

Single Cell Tracking of 3D Epigenetic Landscape Evolution During Embryonic Development
An important question to cell biology is how cells break the symmetry during mitotic divisions. During mammalian
pre-implantation embryonic development (PED), how the first cell fate decision is made remains unclear and is
crucial for the understanding of how specific gene regulations can guide the life of a cell. Epigenetic modifications
including chromatin remodeling are early events during PED. Histone methylation at different residues can recruit
differential sets of chromatin remodeling complexes to regulate chromatin structures and silence/activate gene
expressions accordingly. These histone methylations and their combinations at different genomic loci can serve
as codes to determine the overall gene expression profile and phenotypic outcomes. However, it is still not
understood how histone methylations and hence chromatin structures at specific loci are dynamically regulated
during PED in which cells undergo a heterogeneous modulation at single cell levels. In this proposal, we will
harness the power of directed evolution and high-throughput screening method to systematically develop
specific/sensitive FRET (fluorescence resonance energy transfer) biosensors for the monitoring of crucial histone
methylations in single cells. We will further develop and apply the mapping RNA-chromatin interactions in single
cells (sciMARGI) to identify crucial RNA-genome interaction sites during PED. We will then employ the
endonuclease-deficient Cas9 (dCas9), small guide RNAs (sgRNAs) and split FPs to identify and track the
positons of specific loci crucial for embryonic cell differentiation. Ultimately, we will apply our controllable
epigenetic modulators to guide the histone modulations at specific loci and elucidate their role in determining cell
fates during PED. Given the importance of epigenetic modifications at different loci, the success of the project
should have transformative impact in understanding the role of locus-specific epigenetics in determining the cell
fate during PED. Accordingly, three aims are proposed: Aim 1. Spatiotemporal imaging of crucial histone
methylations in single live cells and during PED; Aim 2. Visualize the locus-specific histone modifications during
PED; Aim 3. Reprogram the locus-specific histone modifications during PED. While the focus of this proposal is
to develop tools targeting histone methylations and chromatin structures at specific loci and differentiation
outcomes, the strategies and approaches can be extended to monitor, in principle, any other epigenetic
modification in single cells, including but not limited to histone acetylation and phosphorylation. The results from
this project can also lead directly to the dynamic nuclear atlas illustrating how specific histone codes are
encrypted in an integrative manner for the regulation of life.

## Key facts

- **NIH application ID:** 10344905
- **Project number:** 1R01HD107206-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Yingxiao Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $679,397
- **Award type:** 1
- **Project period:** 2022-03-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10344905

## Citation

> US National Institutes of Health, RePORTER application 10344905, Single Cell Tracking of 3D Epigenetic Landscape Evolution During Embryonic Development (1R01HD107206-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10344905. Licensed CC0.

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