# Uncovering the Cellular and Molecular Mechanisms Driving B-cell Neogenesis During Regeneration

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA-IRVINE · 2022 · $41,510

## Abstract

Project Summary/Abstract
Diabetes is a growing global health problem that requires improved life-long treatments. A more universal
approach to treat type one diabetes (T1D) would be inducing endogenous cells to restore lost cells. Therefore,
my proposed work aims to discover the cellular and molecular mechanism driving -cell neogenesis to identify
pathways that can be exploited to restore  cells in diabetics. We use zebrafish as a model system because they
have specialized ducal cells called centroacinar cells (CACs) that behave as -cell progenitors. All CACs are
Notch responsive, but cells that have lower Notch activity are more likely to differentiate. All CACs express sox9b,
and our lab has shown that sox9b haploinsufficiency in zebrafish accelerates -cell regeneration. To better
understand the progenitor behavior of CACs, our lab used bulk RNA-seq to uncover the CAC transcriptome.
One major issue with bulk RNA-seq is that it masks CAC heterogeneity and cannot be used to reveal cellular
and molecular mechanisms driving CAC differentiation at the single-cell level. I propose to better understand the
cellular and molecular mechanisms of CACs by addressing two major aims: (1) Characterize cellular
heterogeneity within the CAC population using single-cell RNA-seq and (2) Investigate transcriptome changes
as CACs transition into  cells during regeneration. (1) To characterize the variation in the CAC population, CACs
will be isolated from wild type (WT) adult zebrafish pancreata using fluorescent activated cell sorting (FACS).
Isolated CACs will be subject to scRNA-seq and cluster analysis will be applied to separate the CAC
transcriptomes into distinct subpopulations. (2) I will use a transgenic zebrafish model to induce -cell ablation.
At a halfway-point during regeneration, I will isolate CACs by FACS and will use these CACs for scRNA-seq.
Cluster analysis and pseudotime analysis will be applied to order CACs and identify a mechanism for
regeneration. For both aims, I will perform appropriate in situ experiments to visualize CAC subpopulations and
confirm whether ‘new’ genes identified from my pseudotime model are associated with -cell differentiation. My
project will elucidate the natural variation that exists within the CAC population and will uncover molecular
mechanisms driving -cell regeneration. My lab and others will be able to use my validated data to gain a better
understanding of the potential therapeutic routes that can be exploited to improve the treatment of T1D patients.

## Key facts

- **NIH application ID:** 10455473
- **Project number:** 5F31DK127688-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Tori Raquel Tucker
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $41,510
- **Award type:** 5
- **Project period:** 2021-07-26 → 2023-07-25

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10455473

## Citation

> US National Institutes of Health, RePORTER application 10455473, Uncovering the Cellular and Molecular Mechanisms Driving B-cell Neogenesis During Regeneration (5F31DK127688-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10455473. Licensed CC0.

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