# Probing Tissue Heterogeneity and Stem Cell Niche with Micro-Organospheres

> **NIH NIH R35** · TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION · 2024 · $681,990

## Abstract

Abstract
Stem cells self-renew and differentiate into various cell lineages to sustain tissue homeostasis and functions.
Most tissue microenvironments comprise multiple components, including epithelial, stromal, immune, and
endothelial cells, that interact with each other to coordinate response to intrinsic and extrinsic stimuli. There
remains an unmet need for in vitro models that can capture tissue heterogeneity and enable high-throughput
studies.
The PI developed Micro-OrganoSpheres (MOS) that can be established rapidly and efficiently from small
amounts of primary tissues. Allowing self-renewal and differentiation of adult stem cells to recapitulate key tissue
characteristics, MOS also sustain the original tissue microenvironment, enabling both ultra-high-throughput
assays aided by deep-learning algorithms and direct microbial-host interactions.
For the next R35 period, MOS will be leveraged as a fundamental research tool for understanding interactive
processes in heterogeneous tissues in a systematic and scalable manner. Three projects are proposed:
(1) We will set up a high-throughput MOS screen to systematically study how different cell types in a
heterogenous tissue respond to different microbes.
(2) We will develop a MOS combinatorial indexing technique to probe how cell-cell interactions in local
microenvironments lead to spatially heterogenous tissue responses.
(3) We will use MOS engraftment and intravital imaging to understand cell fate decisions and progression
of stem cell niche from development to adulthood.
The success of these projects will elucidate the mechanisms by which 1) different cells coordinate locally to
respond to stimuli and 2) the stem cell niche progresses during growth. Furthermore, this research will provide
the broader scientific community with basic research techniques that can be generalized to understand a wide
variety of tissue and stem cell functions.

## Key facts

- **NIH application ID:** 10907406
- **Project number:** 5R35GM122465-08
- **Recipient organization:** TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION
- **Principal Investigator:** Xiling Shen
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $681,990
- **Award type:** 5
- **Project period:** 2017-04-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10907406

## Citation

> US National Institutes of Health, RePORTER application 10907406, Probing Tissue Heterogeneity and Stem Cell Niche with Micro-Organospheres (5R35GM122465-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10907406. Licensed CC0.

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