# Regulation of generation and functions of intermediate progenitors

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $430,275

## Abstract

Intermediate progenitors are stem cell progeny that undergo limited proliferation to increase the generation of
differentiated cells per asymmetric stem cell division. Subsets of stem cells appear to have the capability to
further expand the generation of intermediate progenitors via transit-amplifying cell types while other subsets
do not. It is unclear whether the competency to amplify the generation of intermediate progenitors is encoded
in the lineage-specific gene regulatory program or is a general stem cell functionality that can undergo
controlled activation. In addition, stem cell functionalities must become decommissioned in intermediate
progenitors to ensure that they exclusively generate differentiated cell types. The mechanisms that
decommission stem cell-specific functions are not understood. This proposal uses fruit fly neural stem cell
(neuroblast; NB) lineages as a model to define the driver and the barrier to amplify ganglion mother cells
(functional analogs of intermediate progenitors in vertebrates) via intermediate neural progenitors (INPs). We
defined 4332 neurogenic enhancers that likely play important roles in specifying cell type-specific gene
expression in the developing brain. By using this collection of neurogenic enhancers, we identified 43
candidate transcription factors that regulate the competency to generate INPs. In parallel, we also identified 35
transcription factors that likely function to promote decommissioning of type II NB functionality genes genes in
INPs. By initially focusing on these genes, we will begin to define the mechanisms that (1) control NB
competency to generate INPs and (2) decommission NB functionality genes in INPs. Our proposed
experiments will provide insight into how dynamic control of neurogenic enhancers promotes (1) the
competency to expand intermediate progenitors via transit-amplifying cell types and (2) decommissioning of
stem cell-specific functions in intermediate progenitors.

## Key facts

- **NIH application ID:** 10980611
- **Project number:** 1R01NS134942-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Cheng-Yu Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $430,275
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980611

## Citation

> US National Institutes of Health, RePORTER application 10980611, Regulation of generation and functions of intermediate progenitors (1R01NS134942-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10980611. Licensed CC0.

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