# BMP signaling and regenerative plasticity: Correlating dynamic scRNAseq and real-time anatomical remodeling in T1D pancreatic slices

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2024 · $505,793

## Abstract

PROJECT SUMMARY
The cellular plasticity of the human pancreas is implied from multiple scRNAseq studies.
However, these have been invariably based on static datasets from which fate trajectories can
only be inferred using pseudotemporal estimations. Furthermore, the reliance on isolated islet
preparations for the conduct of these analyses has resulted in a drastic underrepresentation of
other non-endocrine cell types, hindering our ability to accurately interrogate exocrine-endocrine
interactions. The long-term culture of human pancreatic slices (HPSs) has presented the field with
an opportunity to sidestep these limitations by longitudinally tracking tissue plasticity at the single-
cell level. Combining single-cell transcriptomic datasets from same-donor HPSs at different time
points, with or without a known regenerative stimulus (BMP signaling), has led to the integration
of dynamic datasets that store true temporal or treatment-dependent information. This novel
approach (Dynamic SliceSeq, or DSSeq for short) has revealed population shifts consistent with
the BMP-mediated progenitor cell activation, the blurring of ductal/acinar boundaries, the
formation of clear ducto-acinar-endocrine differentiation axes and, notably, the appearance of
transitional insulin+ cell populations ‘caught in the act’ of adopting endocrine fates.
Our research is the first to unveil human pancreatic plasticity at the single cell level as a function
of treatment and time. In vitro lineage tracing indicates that BMP signaling also elicits the
formation of functional glucose-responsive insulin+ cells within the exocrine compartment of slices
from type 1 diabetic (t1D) donors. Our first hypothesis is that the path through which these cells
arise in samples from non-diabetic donors will be largely preserved in those with autoimmune
diabetes, and potentially even reinforced as a result of compensatory responses. We further
hypothesize that the ductoacinar-endocrine differentiation axis identified by DSSeq (where
progenitor populations of BMP-stimulated ductal cells differentiate into endocrine cells through an
intermediate acinar-like stage) may mirror the process of embryonic ductal delamination. In
particular, we expect BMP signaling to induce such progenitors to migrate into the acinar
parenchyma prior to their coalescence into islets. To test these hypotheses, we will pursue the
following specific aims: (1) DSSeq analysis of BMP-induced endocrine regeneration in HPSs from
t1D donors; (2) Longitudinal resolution of ductal tissue remodeling and neogenesis of insulin+ cells
within their native histological microenvironment; and (3) Spatial transcriptomics analysis of islet-
duct interfaces in histological samples from nPOD’s t1D collection.
The development of long-term HPS culture techniques, and especially DSSeq, has enabled the
dissection of regenerative responses directly in live tissue from t1D donors with an unprecedented
degree of resolution. The completion of our r...

## Key facts

- **NIH application ID:** 10793083
- **Project number:** 1R01DK138210-01
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Juan Dominguez-Bendala
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $505,793
- **Award type:** 1
- **Project period:** 2024-01-02 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10793083

## Citation

> US National Institutes of Health, RePORTER application 10793083, BMP signaling and regenerative plasticity: Correlating dynamic scRNAseq and real-time anatomical remodeling in T1D pancreatic slices (1R01DK138210-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10793083. Licensed CC0.

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