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Status |
Public on Jun 24, 2024 |
Title |
An in vitro model of acute horizontal basal cell activation reveals dynamic gene regulatory networks underlying the acute activation phase |
Organism |
Rattus norvegicus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Unlike most of the adult nervous system, the olfactory epithelium (OE) can regenerate neurons lost during normal homeostasis or after injury. This life-long regeneration is propagated by two populations of stem cells, the actively proliferating globose basal cells (GBCs) and the dormant horizontal basal cells (HBCs). HBCs only activate and contribute to epithelial regeneration in the context of severe injury, and this activation is mediated by the loss of the transcription factor Tp63. While the HBC differentiation trajectories that occur after activation have been described with lineage tracing and single-cell RNA seq experiments, the immediate consequences of injury on HBC gene expression and fate commitment have not been explored. We present an in vitro model of the acute activation process for HBCs in response to treatment with phorbol 12-myristate 13-acetate (PMA) to explore the molecular underpinnings of these early activation events. We find that treating HBCs with PMA induces the rapid degradation of TP63, and we find that this effect is partially reversed when cells are allowed to recover in maintenance media. Using bulk RNA sequencing we found that PMA-treated HBCs pass through various stages of acute activation identifiable by specific gene regulatory signatures. These transcriptomic phases are associated with varying degrees of plasticity with regards to activated HBCs ability to engraft in transplant models.
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Overall design |
We performed gene expression profiling analysis using data obtained from RNA-seq of three HBC populations at three stages of activation (0H, 6H, and 12H). Cells were activated with 50nM phorbol 12-myristate 13-acetate (PMA).
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Contributor(s) |
Barrios-Camacho CM, Zunitch MJ, Louie JD, Jang W, Schwob JE |
Citation missing |
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Submission date |
Oct 14, 2022 |
Last update date |
Jun 25, 2024 |
Contact name |
Camila Barrios-Camacho |
Organization name |
Tufts University
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Lab |
Schwob
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Street address |
136 Harrison Avenue
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City |
Boston |
State/province |
MA |
ZIP/Postal code |
02111 |
Country |
USA |
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Platforms (1) |
GPL25947 |
Illumina NovaSeq 6000 (Rattus norvegicus) |
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Samples (9)
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GSM6640397 |
HBC, 50nM PMA-treated, 6 hours, rep1 |
GSM6640398 |
HBC, 50nM PMA-treated, 6 hours, rep2 |
GSM6640399 |
HBC, 50nM PMA-treated, 6 hours, rep3 |
GSM6640400 |
HBC, 50nM PMA-treated, 12 hours, rep1 |
GSM6640401 |
HBC, 50nM PMA-treated, 12 hours, rep2 |
GSM6640402 |
HBC, 50nM PMA-treated, 12 hours, rep3 |
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Relations |
BioProject |
PRJNA890628 |
Supplementary file |
Size |
Download |
File type/resource |
GSE215797_DESeq2_normalized_counts_allsamples.csv.gz |
567.7 Kb |
(ftp)(http) |
CSV |
GSE215797_RAW.tar |
1.1 Mb |
(http)(custom) |
TAR (of TAB) |
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Raw data are available in SRA |
Processed data are available on Series record |
Processed data provided as supplementary file |
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