A cell‐type‐specific regulon controlling monoterpene indole alkaloid biosynthesis with feedback and feedforward activation loops
Bibliographic record
Abstract
Monoterpene indole alkaloids (MIA) are a diverse class of plant natural products produced by a subset of lineages within the Asterid clade of eudicots. The diversity of MIAs provides a unique opportunity to study not only the evolution of biosynthetic genes but also their regulation. In this study, we investigate the cell type specificity of biosynthetic genes and coexpressed transcription factors (TFs) in two MIA-producing Asterid species, Catharanthus roseus, a well-studied MIA-producing species, and Camptotheca acuminata, which belongs to an early-diverging lineage of the Asterid clade. We generated single-cell RNA-seq data from the C. acuminata stem, the primary site of camptothecin biosynthesis. We found that MIA biosynthetic genes in C. acuminata are specific to exceptionally rare cell populations. We discovered MYB and bHLH TFs coexpressed in the same cell types as MIA biosynthetic genes in the C. acuminata stem. Interestingly, the C. roseus orthologs of these TFs are idioblast-specific and activate MIA biosynthetic genes in C. roseus upon overexpression. We constructed an extended gene regulatory network for the idioblast metabolic regulon in C. roseus, which contains both feedback and feedforward activation loops. This study demonstrates co-option of the same clades of TFs for regulation of cell-type-specific MIA biosynthesis across two Asterid species separated by c. 115 million years of evolution. Investigating cell-type-specific TFs that are coexpressed with biosynthetic genes across multiple species is a powerful strategy to increase the power for the discovery of plant metabolic regulators.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".