Plant stem cell maintenance involves direct transcriptional repression of differentiation program

• Published in: Molecular systems biology Vol. 9; no. 1; pp. 654 - n/a
• Main Authors: Yadav, Ram Kishor, Perales, Mariano, Gruel, Jérémy, Ohno, Carolyn, Heisler, Marcus, Girke, Thomas, Jönsson, Henrik, Reddy, G Venugopala
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 2013; John Wiley & Sons, Ltd; EMBO Press; Nature Publishing Group; Springer Nature
• Subjects: Arabidopsis - cytology; Arabidopsis - genetics; Arabidopsis - metabolism; Arabidopsis Proteins - genetics; Arabidopsis Proteins - metabolism; Biofysiks; Biologi; Biological Evolution; Biological Sciences; Biophysics; Cell adhesion & migration; Cell Differentiation; Cell division; central zone; Charitable foundations; CLAVATA3; Computer applications; Computer Simulation; Differentiation; EMBO09; EMBO30; Experiments; Gene expression; Gene Expression Regulation, Plant; Gene silencing; Genetic engineering; Genomes; Genomic analysis; Genomics; Homeobox; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Homeostasis; Kinases; Maintenance; Meristem - cytology; Meristem - genetics; Meristem - metabolism; Meristems; Models, Genetic; Natural Sciences; Naturvetenskap; Organs; Plant Cells - metabolism; Plant Leaves - cytology; Plant Leaves - genetics; Plant Leaves - metabolism; Plant Shoots - cytology; Plant Shoots - genetics; Plant Shoots - metabolism; Protein Isoforms - genetics; Protein Isoforms - metabolism; Proteins; Regulatory sequences; shoot apical meristem; stem cell niche; Stem cell transplantation; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic; WUSCHEL; United States > US; stem cell niche; WUSCHEL; CLAVATA3; shoot apical meristem; central zone
• ISSN: 1744-4292; 1744-4292
• DOI: 10.1038/msb.2013.8

In animal systems, master regulatory transcription factors (TFs) mediate stem cell maintenance through a direct transcriptional repression of differentiation promoting TFs. Whether similar mechanisms operate in plants is not known. In plants, shoot apical meristems serve as reservoirs of stem cells that provide cells for all above ground organs. WUSCHEL, a homeodomain TF produced in cells of the niche, migrates into adjacent cells where it specifies stem cells. Through high‐resolution genomic analysis, we show that WUSCHEL represses a large number of genes that are expressed in differentiating cells including a group of differentiation promoting TFs involved in leaf development. We show that WUS directly binds to the regulatory regions of differentiation promoting TFs; KANADI1 , KANADI2 , ASYMMETRICLEAVES2 and YABBY3 to repress their expression. Predictions from a computational model, supported by live imaging, reveal that WUS‐mediated repression prevents premature differentiation of stem cell progenitors, being part of a minimal regulatory network for meristem maintenance. Our work shows that direct transcriptional repression of differentiation promoting TFs is an evolutionarily conserved logic for stem cell regulation. The plant stem cell regulator WUSCHEL is shown to repress differentiation‐promoting transcription factors. This regulatory network is analyzed with a computational model of the three‐dimensional shoot stem cell niche and a combination of genetic perturbation and live imaging. Synopsis The plant stem cell regulator WUSCHEL is shown to repress differentiation‐promoting transcription factors. This regulatory network is analyzed with a computational model of the three‐dimensional shoot stem cell niche and a combination of genetic perturbation and live imaging. We find that the transcription factor (TF) WUSCHEL (WUS) directly binds to the promoters and represses a group of genes including key TFs involved in differentiation thus keeping them repressed in the stem cells of the plant shoot, a mechanistic logic that is similar to animal stem cell regulation. We use a three‐dimensional computational model of the plant shoot stem cell niche to show that the WUS‐mediated repression of the differentiation program along with the previously reported activation of its own negative regulator leads to a robust stem cell homeostasis in a dynamic growth environment. Live imaging of target genes upon transient manipulation of WUS levels is combined with model perturbations to validate the proposed network and to connect it with a large body of previous experimental work.