Organisms capable of dramatic regeneration maintain adult cells that have the flexibility, or plasticity, to change their fate. This feature enables thm build replacement parts, like organs or limbs, to recover from damage or disease. Previous work on the project and other studies have revealed a broad propensity for specialized cells to display some properties of stem cells;they give rise to new cell types in response to injury. The dynamic changes that cells undergo during the transition from one fate to another could reveal the mechanisms that cells employ to enable them to switch their fates. Such insights will reveal basic features of cellular plasticity that could improve regeneration therapy in human cells. However, due to limitations in analyzing the global status of regenerating cells in vivo, little is known about how cells make the traversal from one state to another. The experimental plan proposes to provide a comprehensive view of cells as they transition to new fates during regeneration. The study utilizes plants because the model system provides a rare opportunity to model cellular plasticity. In addition, the mechanisms that regulate plasticity are well conserved across plants and animals and the plant's adept ability to regenerate will illustrate the full potential of cells to change their identity. The proposal takes advantage of a powerful model system that permits continual imaging of regenerating tissue and the analysis of the transcriptional contents of single cells as they traverse fates. This system includes an inventory of active genes for each cell fate, permitting quantitative analyses to track the complex identity of cells as they regenerate. Thus, the complete analysis will generate a model of the trajectory of regenerating cells in order to address basic questions about regeneration: What is the origin of the highly plastic cells that participate in regeneration? Do regenerating cells show proliferative behavior that resembles stem cells? Do fate transitions require losing all identity and reaching a "ground" state or younger developmental stage (dedifferentiation)? Or, do cells traverse directly to new fates? The results will point to processes that can be targeted to make regeneration more efficient. The innovation of profiling the complete transcriptional dynamics of cells and projecting them onto images of regenerating tissue is widely applicable to many developmental model systems. Thus, overall, the proposed work has broad impact on the field of regeneration.

Public Health Relevance

One important goal in therapeutic regeneration is to enhance the ability of existing cells to replace damaged cells. Despite their differences, plants and animals share mechanisms that control a cell's ability to switch identities. The goal of the projec is to use a powerful system in the highly regenerative plant to understand how a cell can change its identity with the aim to provide insights for new approaches in regenerative medicine.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM078279-08
Application #
8639577
Study Section
Development - 1 Study Section (DEV1)
Program Officer
Haynes, Susan R
Project Start
2006-06-19
Project End
2016-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
8
Fiscal Year
2014
Total Cost
$300,318
Indirect Cost
$100,318
Name
New York University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
041968306
City
New York
State
NY
Country
United States
Zip Code
10012
Efroni, Idan; Mello, Alison; Nawy, Tal et al. (2016) Root Regeneration Triggers an Embryo-like Sequence Guided by Hormonal Interactions. Cell 165:1721-33
Rahni, Ramin; Efroni, Idan; Birnbaum, Kenneth D (2016) A Case for Distributed Control of Local Stem Cell Behavior in Plants. Dev Cell 38:635-42
Efroni, Idan; Birnbaum, Kenneth D (2016) The potential of single-cell profiling in plants. Genome Biol 17:65
Efroni, Idan; Ip, Pui-Leng; Nawy, Tal et al. (2015) Quantification of cell identity from single-cell gene expression profiles. Genome Biol 16:9
Para, Alessia; Li, Ying; Marshall-Colón, Amy et al. (2014) Hit-and-run transcriptional control by bZIP1 mediates rapid nutrient signaling in Arabidopsis. Proc Natl Acad Sci U S A 111:10371-6
Bargmann, Bastiaan O R; Vanneste, Steffen; Krouk, Gabriel et al. (2013) A map of cell type-specific auxin responses. Mol Syst Biol 9:688
Bargmann, Bastiaan O R; Marshall-Colon, Amy; Efroni, Idan et al. (2013) TARGET: A Transient Transformation System for Genome-Wide Transcription Factor Target Discovery. Mol Plant 6:978-80
Ristova, Daniela; Rosas, Ulises; Krouk, Gabriel et al. (2013) RootScape: a landmark-based system for rapid screening of root architecture in Arabidopsis. Plant Physiol 161:1086-96
Rosas, Ulises; Cibrian-Jaramillo, Angelica; Ristova, Daniela et al. (2013) Integration of responses within and across Arabidopsis natural accessions uncovers loci controlling root systems architecture. Proc Natl Acad Sci U S A 110:15133-8
Efroni, Idan; Han, Soon-Ki; Kim, Hye Jin et al. (2013) Regulation of leaf maturation by chromatin-mediated modulation of cytokinin responses. Dev Cell 24:438-45

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