# Dynamics of developmental strategies that drive cell identity and plasticity

> **NIH NIH F32** · STANFORD UNIVERSITY · 2020 · $67,446

## Abstract

PROJECT SUMMARY/ABSTRACT
 Misregulation of cell fate and identity is at the crux of human developmental diseases, including
neurological disorders and cancer. The transition from one cell identity to another along a developmental
trajectory is a key control point, yet it is largely unclear how these transitions and cell identities are regulated. To
investigate fundamental principles that direct stem cell fate and identity, this proposal will examine the multipotent
stem cell stomatal lineage in the model system Arabidopsis thaliana. Stomata, whose name derives from ‘mouth’
in Greek, are specialized organs on the surface of the leaf that are comprised of two cells, called guard cells.
Guard cells, and thus stomata, form a pore that opens and closes to enable the exchange of gases with the
atmosphere. Stomata arise from three discrete cell lineage states (i-iii) that are sequentially driven by three
conserved bHLH transcriptional regulators: SPCH, MUTE, and FAMA. Initially, a series of asymmetric cells
divisions that mediate stem cell self-renewal (i) are orchestrated by SPCH, which is followed by a subsequent
cell differentiation event (ii) controlled by MUTE. A final symmetric cell division and maturation event (iii) is driven
by FAMA. Since plant cells are locked in place by their cell walls and the stomatal lineage is found in the
epidermal plane, neighboring cells tell the story of their past divisions, providing a nearly unrivaled opportunity
to examine mechanisms that underlie stem cell fate and identify decisions. Furthermore, the number of stomata
interspersed among interdigitated epidermal cells varies in response to environmental cues. This feature enables
us to examine the range of adaptable regulatory logic in a multipotent stem cell lineage through simple
manipulations of environmental cues. Thus, the stomatal lineage provides key advantages – the ability to readily
analyze and visualize dividing and differentiating cells in an intact, developmentally adaptable tissue. This
proposal thus integrates single-cell systems biology with whole-tissue developmental biology and molecular
genetics approaches to test our central hypothesis that the stomatal lineage consists of lineally related
heterogeneous and adaptable cell states. Aim 1 will analyze the range of heterogeneity in the stomatal cell
lineage, which should extend our understanding of conserved pathways in stomatal development. Aim 2 will
determine molecular mechanisms that confer lineage adaptability (thereby rendering it “flexible”), and it should
reveal insight into molecular mechanisms that promote flexible cell fate decisions. Together, the proposed
experiments should illuminate generalizable strategies in cell fate and re-programming that may be used to
promote human health and ameliorate developmental disorders.

## Key facts

- **NIH application ID:** 9829967
- **Project number:** 5F32GM129918-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Camila Lopez-Anido
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $67,446
- **Award type:** 5
- **Project period:** 2019-01-01 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9829967

## Citation

> US National Institutes of Health, RePORTER application 9829967, Dynamics of developmental strategies that drive cell identity and plasticity (5F32GM129918-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9829967. Licensed CC0.

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