Caldwell, C. | Search bioRxiv

bioRxiv2026

Diverse Intestinal Injuries Drive Heterogeneous Transcriptional Responses and Limited Reactivation of Developmental Gene Programs in Human Enteroids

The murine intestine reactivates developmental gene programs following various forms of damage in vivo and in vitro; however, injury response mechanisms used by the human intestine remain unclear. Using adult human small intestinal epithelium-only organoids ("enteroids"), we characterized the early response to eight injury conditions and injury-associated signaling pathways (P53, PGE2, YAP, TGFB) to interrogate whether human developmental genes were activated. P53 activation and decreased proliferation were common features across treatments. Most (7/8) injuries did not activate human development genes. Butyrate is a notable exception given it inhibited P53 and promoted a human developmental transcriptional signature. We observe that P53 induces a human adult gene signature while TGFB and YAP promote a developmental signature. Together our data characterizes various transcriptional responses to injury, supports injury-associated signaling pathways as regulators of human adult and developmental genes, and highlights how our data can be mined to predict injury-specific interventions for epithelial protection.

cell biology↗

bioRxiv2022

The NIN-LIKE PROTEIN 7 (NLP7) transcription factor modulates auxin pathways to regulate root cap development

The root cap surrounds the root tip and promotes root growth by protecting the root apical meristem, influencing root branching, and sensing environmental signals like nitrate. The root cap maintains a constant size through the coordination of cell production in the root meristem with cell release at the tip of the root, a process that requires an auxin minima in the last layer of the root cap. To perform its functions, the root cap must maintain a constant size and synchronize external cues with development, but mechanisms underlying such coordination are not well understood. Mutations in the NIN LIKE PROTEIN 7 (NLP7) transcription factor, a master regulator of nitrate signaling, lead to defects in root cap cell release and cell production. Nitrate impacts root development through crosstalk with auxin. Therefore, we hypothesized that NLP7 regulates root cap cell release and cell production by modulating auxin pathways. Here we show that mutations in NLP7 abolish the auxin minima required for root cap cell release and alter root cap expression levels of the auxin carriers PIN-LIKES 3 (PILS3) and PIN-FORMED 7 (PIN7). We find that NLP7 is required for proper root cap cell production and differentiation and for expression of transcription factors that regulate these processes. Nitrate deficiency impacts auxin pathways in the last layer of the root cap, and this is mediated in part by NLP7. Together, our data suggest that NLP7 integrates nitrate signaling with auxin pathways to optimize root cap development in response to external nitrate cues. One sentence summaryThe nitrate master regulator NLP7 controls root cap development through auxin pathways.

plant biology↗