Protein complex stoichiometry and expression dynamics of transcription factors modulate stem cell division

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 117; no. 26; pp. 15332 - 15342
• Main Authors: Clark, Natalie M., Fisher, Adam P., Berckmans, Barbara, Van den Broeck, Lisa, Nelson, Emily C., Nguyen, Thomas T., Bustillo-Avendaño, Estefano, Zebelle, Sophia G., Moreno-Risueno, Miguel A., Simon, Rüdiger, Gallagher, Kimberly L., Sozzani, Rosangela
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 30-06-2020
• Subjects: Arabidopsis - genetics; Arabidopsis - metabolism; Arabidopsis Proteins - chemistry; Arabidopsis Proteins - metabolism; Biological Sciences; Biomarkers; Cell Differentiation; Cell division; Differential equations; Gene Expression Regulation, Plant - physiology; Gene regulation; Homeobox; Models, Biological; Mutation; Ordinary differential equations; Proteins; Stem cells; Stem Cells - physiology; Stoichiometry; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; Upstream; mathematical modeling; transcription factor; protein complex stoichiometry; intercellular protein movement; expression dynamics
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2002166117

Stem cells divide and differentiate to form all of the specialized cell types in a multicellular organism. In the Arabidopsis root, stem cells are maintained in an undifferentiated state by a less mitotically active population of cells called the quiescent center (QC). Determining how the QC regulates the surrounding stem cell initials, or what makes the QC fundamentally different from the actively dividing initials, is important for understanding how stem cell divisions are maintained. Here we gained insight into the differences between the QC and the cortex endodermis initials (CEI) by studying the mobile transcription factor SHORTROOT (SHR) and its binding partner SCARECROW (SCR). We constructed an ordinary differential equation model of SHR and SCR in the QC and CEI which incorporated the stoichiometry of the SHR-SCR complex as well as upstream transcriptional regulation of SHR and SCR. Our model prediction, coupled with experimental validation, showed that high levels of the SHR-SCR complex are associated with more CEI division but less QC division. Furthermore, our model prediction allowed us to propose the putative upstream SHR regulators SEUSS and WUSCHEL-RELATED HOMEOBOX 5 and to experimentally validate their roles in QC and CEI division. In addition, our model established the timing of QC and CEI division and suggests that SHR repression of QC division depends on formation of the SHR homodimer. Thus, our results support that SHR-SCR protein complex stoichiometry and regulation of SHR transcription modulate the division timing of two different specialized cell types in the root stem cell niche.