# Elucidating ECM Signaling in Cardiac Organoids with Machine Learning and Single-cell Multiomics

> **NIH NIH R01** · STANFORD UNIVERSITY · 2024 · $599,103

## Abstract

Project Summary
Extracellular matrix (ECM) is the most abundant biomaterial in the body. During cardiac development, the ECM
plays critical roles in the formation of shapes and patterns of the heart such as chambers and trabeculae through
elaborate interactions with differentiating cells. Although problems in ECM-cell interactions can lead to heart
diseases, signaling pathways activated by the specific ECM components are still poorly understood. We recently
succeeded in developing human induced pluripotent stem cell-derived cardiac organoids (iPSC-COs) that can
recapitulate cardiogenesis. In this multi-PI R01 proposal, our team will further elucidate the mechanisms of ECM-
cell interactions that influence cardiac differentiation and morphogenesis. We will apply machine learning and
novel iPSC double reporter lines (Tbx5-Clover2-Nkx2.5-TagRFP) to elucidate the effect of cell composition on
morphogenesis of iPSC-COs (Aim 1). Afterwards, we will screen 36 different combinations of ECM compositions
that can reliably induce iPSC-CO formation using 8 additional iPSC lines for validation (Aim 2). By rigorously
analyzing iPSC-COs made with optimized ECM using elastic property measurement and single-cell multiomics,
we will elucidate the biological and physical effects associated with ECM signaling and mechanotransduction at
single-cell resolution (Aim 3). In summary, understanding the exact role and mechanism of ECM-cell interactions
may contribute to finding new biomaterials or therapeutic modalities for treatment of heart diseases.

## Key facts

- **NIH application ID:** 10832010
- **Project number:** 5R01HL163680-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** JAYAKUMAR RAJADAS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $599,103
- **Award type:** 5
- **Project period:** 2022-05-09 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10832010

## Citation

> US National Institutes of Health, RePORTER application 10832010, Elucidating ECM Signaling in Cardiac Organoids with Machine Learning and Single-cell Multiomics (5R01HL163680-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10832010. Licensed CC0.

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