# High resolution 3D mapping of cellular heterogeneity within multiple types of mineralized tissues

> **NIH NIH U54** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2022 · $535,000

## Abstract

Overall Abstract:
The goal of the HuBMAP program is to appreciate the unique contextual role of individual cells within the 3D
structure of a tissue at its most basic level of transcriptional activity, cellular signaling and cellular response.
To date the subject tissues have not included the mineralized skeletal system due to technical issues that
preclude the requirements of the HuBMAP program. We have solved those issues with a protocol that is
capable of performing multimodal histology that include methods for advanced and repetitive in situ
hybridization. We will develop this technology for three very different mineralized skeletal tissues: tooth,
trabecular bone and cartilage structures of the knee. The Coordination Core will acquire the three tissue types
from de-identified human sources. Each sample will be oriented to its source tissue, imaged by µCT to capture
its mineral structure and processed into a histological stack to create a 3D representation of the tissue. Using
the histological stack, the Mineralized Tissue Program will perform both in situ hybridization to identify the
multiple cell types and seqFISH hybridization to capture the cell transcriptome of the identified cell types.
These technically demanding steps will require direction from established HuBMAP investigators as well as
UConn faculty who are experts in high resolution confocal microscopy. The Data Analysis Core will translate
the image files generated by these techniques into 3D cellular maps of the target tissue and transcriptome
composition of each cell type. From those data files, our contextual molecular mapping program, TOPAS, will
examine the transcriptional and signaling pathways to impute how neighboring cells coordinate their activities
to respond to mechanical loading and systemic factors that regulate skeletal health. The workflow and
analytical platforms that we developed for the skeletal system will be aligned with the requirement of the HIVE
including an outreach initiative. First, we will provide opportunities to transfer the histological technology to
major academic skeletal research groups. Second, once our skeletal data becomes available from the central
HIVE source, we will develop virtual workshops to inform the skeletal biology community of this valuable
resource and how it can be utilized to unravel rare diseases affecting the skeleton. HuBMAP will be a
transformational technology that every tissue centric group needs to incorporate. Our role is to ensure that the
skeletal biology community is included in this new experimental platform, and that it is employed to solve the
major genetic and therapeutic challenges affecting skeletal health.

## Key facts

- **NIH application ID:** 10700252
- **Project number:** 4U54AR078664-03
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Martin K Lotz
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $535,000
- **Award type:** 4N
- **Project period:** 2020-09-21 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10700252

## Citation

> US National Institutes of Health, RePORTER application 10700252, High resolution 3D mapping of cellular heterogeneity within multiple types of mineralized tissues (4U54AR078664-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10700252. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*