# Single-cell transcriptomic analysis of sibling progenitors with differential Notch activity

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $444,125

## Abstract

PROJECT SUMMARY
It has been observed across species that embryonic radial glia neural progenitors undergo asymmetric cell
division (ACD) to generate daughter cells with different Notch activity. The Notchhi daughter undergoes self-
renewal, whereas the Notchlo daughter embarks on differentiation. Being able to molecularly define such different
states will significantly advance our understanding of how self-renewal and differentiation are regulated.
 Although the relative Notch activity levels between embryonic daughters are correlated with their self-
renewing vs. differentiation potential, the absolute Notch activity is heterogeneous across the progenitor
population. This makes it impossible to simply sort single-cell RNA-seq (scRNA-seq) data based on the
expression levels of Notch effectors (e.g. hes/her transcript levels). It is therefore important to track the lineage
relationships among progenitors precisely at the level of sibling cells in scRNA-seq experiments.
 This exploratory R21 application, motivated by an important biological problem, aims to establish high
resolution sib lineage-tracing and combine it with scRNA-seq. This represents a technological breakthrough that
will enable comparison of gene expression profiles between sibling cells.
 Expected outcomes and impact: If successful, this project will establish a new and broadly
applicable method in which sib cell states can be compared at the transcriptomic level both in vivo and
in vitro. By applying this method to embryonic radial glia progenitors that are undergoing asymmetric cell
division during active neurogenesis, we expect to uncover evolutionarily conserved core genes and pathways
distinguishing Notchhi and Notchlo sib states that are shared across sib-lineages. Since Notchhi and Notchlo sib
states are associated with self-renewal and differentiation respectively in embryonic progenitors, we expect to
gain a glimpse into whether and how self-renewal and differentiation as distinct cellular states can be depicted
at the transcriptomic level that are uncoupled from specific lineage outcomes. We will make this novel
dataset with precise clonal tracking widely available to the broad research community.
 This project will lay foundation for a future R01, which aims to dissect the function of signature genes
and pathways that define Notchhi vs. Notchlo cell states. In the long run, new basic knowledge about the
underlying genetic programs will aid in developing new therapeutic ideas. The high risk and high reward nature
of the proposed work makes this application well suited for the R21 mechanism.

## Key facts

- **NIH application ID:** 10372848
- **Project number:** 1R21NS122053-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Su Guo
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $444,125
- **Award type:** 1
- **Project period:** 2021-09-30 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10372848

## Citation

> US National Institutes of Health, RePORTER application 10372848, Single-cell transcriptomic analysis of sibling progenitors with differential Notch activity (1R21NS122053-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10372848. Licensed CC0.

---

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