# Establishment, maintenance, and consequences of asymmetric cell division in T cells

> **NIH NIH R01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2020 · $448,750

## Abstract

Abstract
Polarizing cues during mitosis can result in the process of asymmetric cell division (ACD), in which molecules
differentially segregate to the two daughters. ACD has important functions in differentiation and development,
with critical roles in stem cell renewal, and has been described following activation of T and B lymphocytes. In
T cells, ACD can apparently result in daughters with distinct functional cell fates. We have found that in CD8+
T cells, ACD is associated with asymmetric segregation of c-Myc in telophase, which is then maintained in first
division daughter cells. Further, we have found that the distribution of amino acid transporters, amino acid
levels, TORC1 activity, and c-Myc correlate as activated T cells undergo the first round of division, and the
maintenance of the differential c-Myc levels depends on amino acid availability, glutaminolysis, and TORC1
activity. This application is based on our central hypothesis that asymmetry, established via the coordinate
polarization of surface molecules, including amino acid transporters, to the site of T cell receptor (TCR)
activation, creates a metabolic, feed-forward process that sustains TORC1, c-Myc, epigenetics, and cell fate.
To explore this hypothesis in detail, we will ask: 1. How is asymmetric division in CD8+ T lymphocytes
established? Here we will examine the initial events that lead to asymmetric assortment of amino acid
transporters, TORC1, and c-Myc upon the first division in CD8+ T lymphocytes, testing the idea that it is the
polarization of the microtubule organizing center, transporters, and TORC1 activity that drives ACD. We will
explore roles for the interactions of TCR signaling components, cytoskeleton, and the translation machinery in
the asymmetrical distribution of these critical determinants of T lymphocyte fate, and examine how they
influence the function and expression of TORC1, c-Myc, and other asymmetrically-distributed functional
molecules. 2. How is asymmetry, once established, maintained in the daughter cells and their progeny?
Based on our data, we hypothesize that metabolic differences in the daughters arising from ACD, established
by asymmetric assortment of amino acid transporters, maintains and consolidates asymmetry via feed-forward
mechanisms. We will perturb the elements of this positive feed-back pathway to alter the phenotypes and
functions of either daughter, and examine roles for translation, transcription, and epigenetic changes in
maintaining asymmetry. 3. What are the roles of asymmetry in the first division of CD8+ T cells in vivo?
The daughters of asymmetric division of T cells appear to be endowed with distinct fates, characterized by
effector-like and memory-like properties, however the contribution of ACD to immune responses remains
controversial. We will employ approaches to barcoding, single cell mRNA expression, and lineage tracing to
examine how cells that are apparently committed to a cell fate may be re-directed to a dif...

## Key facts

- **NIH application ID:** 9875425
- **Project number:** 5R01AI123322-04
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Douglas R. Green
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $448,750
- **Award type:** 5
- **Project period:** 2017-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9875425

## Citation

> US National Institutes of Health, RePORTER application 9875425, Establishment, maintenance, and consequences of asymmetric cell division in T cells (5R01AI123322-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9875425. Licensed CC0.

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