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Spatial transcriptomic sequencing of repaired lung transplanted with human P63+ progenitor [STOmics-seq]

ABSTRACT: Spatial transcriptomic sequencing of repaired lung transplanted with human P63+ progenitor [STOmics-seq]

PROVIDER: PRJNA1083473 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28214618.fastq.gz	Fastqsanger.gz
	SRR28214619.fastq.gz	Fastqsanger.gz
	SRR28214620.fastq.gz	Fastqsanger.gz
	SRR28214621.fastq.gz	Fastqsanger.gz
	SRR28214622.fastq.gz	Fastqsanger.gz

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Spatial transcriptomic sequencing of repaired lung transplanted with human P63+ progenitor [STOmics-seq]

Project description:KRT5+P63+ progenitor cells located in the basal layer of the airway epithelium have been identified as a promising candidate for lung epithelium repair. Such cells are originated from primitive progenitors in distal airways and could expand/migrate to inflamed damaged lung parenchymal region to form ‘saccule’. To further investigate the characteristics and potential function of the saccule structure, we performed the high-resolution spatial transcriptomic analysis on the 35 dpt lung section.

2024-12-19 | GSE260779 | GEO

Autologous transplantation of P63+ lung progenitor cells for chronic obstructive pulmonary disease therapy

Project description:Adult lung resident stem/progenitor cells, including P63+ progenitor cells, have demonstrated the capacity for regeneration of lung epithelium in precinical models. Here we report a clinical trial of intra-pulmonary P63+ progenitor cell transplantation which included 28 participants with chronic obstructive pulmonary disease (COPD) (stage II~IV). For control group, standard of care (SOC) for COPD treatment was given. For intervention group, in addition to SOC, autologous P63+ progenitor cells were isolated from the airway basal layer via bronchoscopic brushing, cultured for 3~5 weeks, and then transplanted into the lungs via bronchoscopy with 0.7-5.2x10^6 cells per kilogram bodyweight. Eventually 20 patients were evaluated (intervention group n=17; control group n=3). No grade 3~5 adverse events (AE) or serious adverse events occurred in any group. Bronchoscopy-associated AEs were recorded only in intervention groups, while the other AEs were recorded in both groups without showing significant difference. Participants in intervention group displayed significant improvement in diffusing capacity of the lung for carbon monoxide (DLCO) (change from baseline, 24 weeks: +18.2%), showing significant difference comparing to control group (change from baseline, 24 weeks: -17.4%)(p-value=0.008). Furthermore, more participants in intervention group showed > 30 m increase in walking distance within 6 minutes, demonstrating significant difference comparing to control group (p-value=0.036). Transcriptomic analysis of cells isolated from responding and non-responding individuals in the intervention group showed that higher expression of P63 and Nkx homeobox-1 was associated with better efficacy. In conclusion, transplantation of cultured P63+ lung progenitor cells was safe and represented a potential treatment strategy for COPD.

2024-01-20 | GSE236438 | GEO

Spatial transcriptomic analysis of transplanted vascularized lung organoids

Project description:To investigate the cell-cell interactions among the transplanted vascularized organoids, we utilized a Slide-seq-based spatial transcriptomics platform to unbiasedly map the spatial distribution of ligand-receptor pairs.

2025-06-29 | GSE296429 | GEO

Fate mapping of human P63+ progenitor in vivo by single cell transcriptomic analysis [scRNA_seq]

Project description:KRT5+P63+ progenitor cells located in the basal layer of the airway epithelium have been identified as a promising candidate for lung epithelium repair. To gain molecular insights into the fate specification process of human P63+ progenitor cells in the lung, we sorted the transplanted GFP+ cells at different time points using flow cytometry, followed by 10x Genomics single-cell RNA sequencing analysis. Unsupervised clustering of the cells resulted in the identification of 7 distinct populations.

2024-12-19 | GSE260778 | GEO

Cloning and comparison of human P63+ progenitor cells from various lung diseases [bulkRNA-seq]

Project description:KRT5+P63+ progenitor cells located in the basal layer of the airway epithelium have been identified as a promising candidate for lung epithelium repair. To investigate P63+ progenitor cells in human, we cloned KRT5+P63+ progenitors from both healthy donors and patients with various lung diseases.

2024-12-19 | GSE260777 | GEO

Spatial transcriptomic analysis of transplanted vascularized lung organoids

Project description:Spatial transcriptomic analysis of transplanted vascularized lung organoids

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p63+/Krt5+ Distal Airway Stem Cells are Essential for Lung Regeneration (transplanted and damaged)

Project description:The possibility of lung regeneration has been long discounted due to the irreversible nature of chronic lung diseases. However, patients who sustain massive loss of lung tissue during acute infections often recover full pulmonary function. Correspondingly, we previously demonstrated lung regeneration in mice following H1N1 influenza virus infection and implicated p63+Krt5+ distal airway stem cells, or DASCp63/Krt5, in this process. We show here that rare, preexisting DASCp63/K5 undergo a proliferative expansion in response to influenza and lineage-trace to nascent alveoli assembled at sites of interstitial inflammation. We also show that the ablation of DASCp63/Krt5 in vivo prevents the regeneration of lung tissue following influenza leading to pre-fibrotic lesions and deficient oxygen exchange. Finally, we demonstrate that exogenously cloned and propagated DASCp63/Krt5 readily contribute to lung regeneration following transplantation. The transplanted DASC ameliorated influenza-induced lung injury. These data suggest that DASCp63/K5 are required for lung regeneration and may have therapeutic utility in acute and chronic lung diseases. Transplanted DASC cells incorporated into damaged host lung were laser capture microdissected and analyzed. Duplicate mice were included. We used the Affymetrix Mouse Exon 1.0 ST platform

2014-11-20 | E-GEOD-60830 | biostudies-arrayexpress

Autologous transplantation of P63+ lung progenitor cells in patients with bronchiectasis: a randomized, single-blind, controlled trial

Project description:Non-cystic fibrosis bronchiectasis is a severe respiratory disease characterized by progressive loss of lung function, resulting in high morbidity and even early mortality. Current treatments cannot repair progressive lung damage, which encouraged the exploration of stem and progenitor cell-based regenerative therapies. In current study, we found that the P63+ progenitor cells normally located in airway basal layer could appear in the alveolar spaces of bronchiectasis patients. We successfully cloned and expanded the progenitor cells from the airway brushing tissues of patients. Then we conducted a randomized, single-blind, controlled, phase 1/2 trial to evaluate the safety and efficacy of autologous P63+ progenitor cells transplantation in bronchiectasis patients.

2024-10-15 | GSE261102 | GEO

p63+/Krt5+ Distal Airway Stem Cells are Essential for Lung Regeneration (transplanted and damaged)

2014-11-20 | GSE60830 | GEO

Single cell RNA sequencing analysis of P63+ lung progenitor cells isolated from IPF patients

Project description:To gain molecular insights into the identity composition of the cells selectively grown in the culture system, we performed single-cell sequencing on the primary cell. Unsupervised clustering of the cells uncovered 3 distinct subpopulations:C1, C2 and C3. Altogether the data indicated that the current cell isolation and expansion system could efficiently enrich P63+ lung progenitor cells from IPF patients.

2024-12-19 | GSE269794 | GEO

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