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.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Development - 1 Study Section (DEV1)
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Haynes, Susan R
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New York University
Schools of Arts and Sciences
New York
United States
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Birnbaum, Kenneth D (2018) Power in Numbers: Single-Cell RNA-Seq Strategies to Dissect Complex Tissues. Annu Rev Genet 52:203-221
Ortiz-Ramírez, Carlos; Arevalo, Edgar Demesa; Xu, Xiaosa et al. (2018) An Efficient Cell Sorting Protocol for Maize Protoplasts. Curr Protoc Plant Biol 3:e20072
Birnbaum, Kenneth D; Roudier, François (2017) Epigenetic memory and cell fate reprogramming in plants. Regeneration (Oxf) 4:15-20
Efroni, Idan; Birnbaum, Kenneth D (2016) The potential of single-cell profiling in plants. Genome Biol 17:65
Efroni, Idan; Mello, Alison; Nawy, Tal et al. (2016) Root Regeneration Triggers an Embryo-like Sequence Guided by Hormonal Interactions. Cell 165:1721-1733
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; 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

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