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An in vitro model of acute horizontal basal cell activation reveals dynamic gene regulatory networks underlying the acute activation phase

ABSTRACT: An in vitro model of acute horizontal basal cell activation reveals dynamic gene regulatory networks underlying the acute activation phase

PROVIDER: PRJNA890628 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21906827_1.fastq.gz	Fastqsanger.gz
	SRR21906827_2.fastq.gz	Fastqsanger.gz
	SRR21906828_1.fastq.gz	Fastqsanger.gz
	SRR21906828_2.fastq.gz	Fastqsanger.gz
	SRR21906829_1.fastq.gz	Fastqsanger.gz

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An in vitro model of acute horizontal basal cell activation reveals dynamic gene regulatory networks underlying the acute activation phase

Project description: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.

2024-06-24 | GSE215797 | GEO

Epigenomic Profile of Lineage-Traced Mouse Horizontal Basal Cells Before and 24 Hours After Injury

Project description:Wild-type horizontal basal cells (HBCs) from mouse olfactory epithelium were profiled using single-cell ATAC-seq (10x Genomics v2) to identify regions of accessible chromatin in individual cells before and 24 hours after acute injury.

2023-10-30 | GSE246167 | GEO

Olfactory stem cell differentiation: horizontal basal cell (HBC) lineage

Project description:The lineage of the horizontal basal cells (HBC) stem cells and other Sox2eGFP-positive cells from the olfactory epithelium were profiled by single-cell RNA-Seq to identify differentiated cells types, intermediate stages, transition states, and to infer the lineage trajectories.

2017-04-14 | GSE95601 | GEO

An in vitro model of acute horizontal basal cell activation reveals gene regulatory networks underlying the nascent activation phase.

Project description:While horizontal basal cells (HBCs) make minor contributions to olfactory epithelium (OE) regeneration during homeostatic conditions, they possess a potent, latent capacity to activate and subsequently regenerate the OE following severe injury. Activation requires, and is mediated by, the downregulation of the transcription factor (TF) TP63. In this paper, we describe the cellular processes that drive the nascent stages of HBC activation. The compound phorbol 12-myristate 13-acetate (PMA) induces a rapid loss in TP63 protein and rapid enrichment of HOPX and the nuclear translocation of RELA, previously identified as components of HBC activation. Using bulk RNA sequencing (RNA-seq), we find that PMA-treated HBCs pass through various stages of activation identifiable by transcriptional regulatory signatures that mimic stages identified in vivo. These temporal stages are associated with varying degrees of engraftment and differentiation potential in transplantation assays. Together, these data show that our in vitro HBC activation system models physiologically relevant features of in vivo HBC activation and identifies new candidates for mechanistic testing.

| S-EPMC11368683 | biostudies-literature

Transcriptomic analysis of in vitro cultured horizontal basal cells of the murine olfactory epithelium

Project description:We report bulk RNAseq of in vitro cultured horizontal basal cells, and in vivo isoalted respiratory basal cells of the murine olfactory epithelium, and compared their profiles with pre-existing bulk RNAseq of in vivo isolated HBCs and single cell RNAseq of in vivo HBCs.

2019-02-01 | GSE103577 | GEO

Olfactory stem cell-mediated regeneration: horizontal basal cell (HBC) lineage [scRNA-seq]

Project description:The lineage of the horizontal basal cells (HBC) stem cells and their descendants from the olfactory epithelium were profiled by single-cell RNA-Seq to identify differentiated cell types, intermediate stages, transition states, and to infer the lineage trajectories.

2017-10-30 | GSE99251 | GEO

Quiescent horizontal basal stem cells act as a niche for olfactory neurogenesis in a 3D organoid model

Project description:The olfactory epithelium contains two basal stem cell populations that facilitate the normally life-long ability for neuronal regeneration that is required for maintaining our sense of smell over the long term. Horizontal basal cells (HBCs) are generally quiescent and only become active after direct injury to the epithelium that kills more than just the olfactory sensory neurons (OSNs). Globose basal cells (GBCs) lie apical to HBCs and are solely responsible for the ongoing generation of olfactory neurons in the undamaged epithelium. Understanding how these two neurogenic stem cell populations are regulated as OSNs are replenished is hampered by a lack of robust culture models. Here, we report the development of a 3-dimensional organoid model that recapitulates the neurogenic cascade while maintaining both HBCs and GBCs in culture. We use this model to demonstrate that despite their relative quiescence, HBCs form a critical niche for the emergence and composition of the organoid.

2025-05-18 | GSE257536 | GEO

Epigenomic Profile of Lineage-Traced Mouse Horizontal Basal Cells Before and 24 Hours After Injury

Project description:Epigenomic Profile of Lineage-Traced Mouse Horizontal Basal Cells Before and 24 Hours After Injury

| PRJNA1031944 | ENA

bulk RNAseq of uninjured and 18 hours post-methyl bromide lesion FACS Horizontal basal cells (HBCs)

Project description:RNAseq analysis of uninjured vs 18hpl injured HBCs show heterogeneous modulation of pathways associated with quiescent stem cell activation. HBCs are the trp63 expressing, quiescent basal stem cell in the olfactory epithelium.

2017-06-08 | GSE92779 | GEO

Sall3 controls cone photoreceptor and horizontal cell differentiation

Project description:Transcription factors have been implicated in the specification and differentiation of all cells in the mammalian retina with several transcription factors controlling the development of multiple neuronal subclasses. Horizontal cells and cone photoreceptors share a particularly intimate functional relationship but have been previously thought to develop through separate and distinct intrinsic molecular processes. We demonstrate that the zinc finger transcription factor Sall3 regulates development of both S-cone photoreceptors and horizontal cells. Our data shows that loss of function of Sall3 down-regulates the horizontal cell specific transcription factor Lhx1 and subsequently causes ectopic formation of horizontal-like wide-field amacrine cells partially phenocopying Lhx1-/- mice. Additionally, horizontal cells which laminate appropriately in Sall3 knockout mice show abnormal horizontal cell gene expression and failures in dendritic arborization. Over-expression of Sall3 also partially re-specifies cells to a horizontal-like wide-field amacrine fate. Intriguingly, Sall3 loss of function experiments also generated a massive reduction in the number of S-cone photoreceptors with remaining S-cones showing deficiencies in S-cone gene expression and morphology. Conversely, over-expression of Sall3 resulted in the ectopic expression of the S-cone specific genes S-opsin (Sop) and cone arrestin (Arr3) in electroporated cells. Our studies reveal that Sall3 regulates aspects of horizontal cell development in two ways: first, by maintaining Lhx1 expression, and second, by directly regulating expression of horizontal cell specific genes. We also show that Sall3 is an essential regulator of S-cone development in the mammalian retina and a potent activator of Sop and Arr3.

2011-09-10 | GSE24083 | GEO

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