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Identification of mesenchymal cell populations during neonatal lung development

ABSTRACT: Identification of mesenchymal cell populations during neonatal lung development

PROVIDER: PRJNA1087350 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28334354_1.fastq.gz	Fastqsanger.gz
	SRR28334354_2.fastq.gz	Fastqsanger.gz
	SRR28334355_1.fastq.gz	Fastqsanger.gz
	SRR28334355_2.fastq.gz	Fastqsanger.gz
	SRR28334356_1.fastq.gz	Fastqsanger.gz

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Identification of mesenchymal cell populations during neonatal lung development

Project description:Alveologenesis is the final stage of lung development in which the internal surface area of the lung is increased to facilitate efficient gas exchange in the mature organism. The first phase of alveologenesis involves the formation of septal ridges (secondary septae) which are covered by alveolar type 1 (AT1) and alveolar type 2 (AT2) cells and contain mesenchymal cells, capillaries, and an elastin rich extracellular matrix (ECM). The second phase involves thinning of the alveolar septa. Mesenchymal cells include a transient population of alveolar myofibroblasts (MyoFB) and a stable but poorly described population of lipid rich cells that have been referred to as lipofibroblasts or matrix fibroblasts (MatFB). Using a unique Fgf18CreER lineage trace mouse line, cell sorting, single cell RNA sequencing, and primary cell culture, we have identified multiple subtypes of mesenchymal cells in the neonatal lung, including an immature progenitor cell that gives rise to mature MyoFB. We also show that the endogenous and targeted ROSA26 locus serves as a sensitive reporter for MyoFB maturation. These studies increase the known repertoire of mesenchymal cell types in the neonatal lung, identify potential intercellular signals, and provide a neonatal time point for comparison with embryonic and adult lung mesenchymal cell subtypes.

2024-04-17 | GSE261508 | GEO

Mesenchymal stromal cells from neonatal tracheal aspirates demonstrate a pattern of gene expression consistent with a lung origin

Project description:Expression profiling of lung derived mesenchymal stromal cells to lung fibrblasts and cord blood derived mesenchymal stromal cells We have previously isolated mesenchymal stromal cells (MSCs) from the tracheal aspirates of premature neonates with respiratory distress. While isolation of MSCs correlates with the development of bronchopulmonary dysplasia, the physiologic role of these cells remains unclear. To address this, we further characterized the cells, focusing on the issues of gene expression, origin and cytokine expression. Microarray comparison of early passage neonatal lung MSC gene expression to cord blood MSCs and human fetal and neonatal lung fibroblast lines demonstrated that the neonatal lung MSCs differentially expressed 971 gene probes compared to cord blood MSCs, including the transcription factors Tbx2, Tbx3, Wnt5a, FoxF1 and Gli2, each of which have been associated with lung development. Compared to lung fibroblasts, 710 gene probe transcripts were differentially expressed by the lung MSCs, including IL-6 and IL-8/CXCL8. Further, neonatal lung MSCs exhibited a pattern of Hox gene expression distinct from cord-blood MSCs but similar to human fetal lung fibroblasts, consistent with a lung origin. Together, these data suggest that MSCs isolated from neonatal tracheal aspirates originate in the lung and are distinct from lung fibroblasts.

2010-10-08 | E-GEOD-24583 | biostudies-arrayexpress

Heterogeneous mesenchymal cell types modulate neonatal lung development and its response to hyperoxia

Project description:During the first days of life, the lung surface area increases explosively to enable efficient oxygen exchange. Alveolarization and angiogenesis involve profound changes within the lung mesenchyme to modulate extracellular matrix composition, tissue elasticity, and coordination with the lung epithelium and endothelium. To define the cell types and states populating the perinatal lung mesenchyme, we performed single cell transcriptomics and in-situ imaging in mice and discovered an extremely heterogeneous and dynamic landscape of fibroblasts, airway smooth muscle-like, and mural cells spanning fourteen distinct populations. In the fibroblast and airway smooth muscle-like compartments, bipotent progenitors differentiate rapidly within one day of birth and then again towards the end of alveolarization, while mural cell types are characterized by slow, gradual changes. Glucocorticoid release, retinoic acid inactivation, and oxygen sensing are controlled by specific stromal progenitors. A population of myofibroblasts arises postnatally, peaks at the onset of alveolarization and disappears before three weeks of age. Paracrine signaling with dozens of lung cell types decreases after birth and especially during alveolarization. Nonetheless, alveolarization is the most proliferative developmental stage, followed by a shift towards cell quiescence. Exposure to hyperoxia during the first week of life delayed the transcriptomic changes of normal development, mirroring the arrested development observed in human neonatal bronchopulmonary dysplasia (BDP). Hyperoxia also caused a severe loss of pericytes and myofibroblasts and reduced their proliferation, decreased mesenchymal-endothelial communications, gave rise to a small novel population of contractile alveolar fibroblasts and increased matrix adhesion and contractility across the mesenchyme.

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Heterogeneous mesenchymal cell types modulate neonatal lung development and its response to hyperoxia

Project description:Heterogeneous mesenchymal cell types modulate neonatal lung development and its response to hyperoxia

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Endothelial to Mesenchymal Transition in Neonatal Hyperoxic Lung Injury: Role of sex as a biological variable

Project description:Bronchopulmonary dysplasia (BPD) is characterized by an arrest in alveolarization, abnormal vascular development and variable interstitial fibroproliferation in the premature lung. Endothelial to mesenchymal transition (Endo-MT) may be a source of pathologic fibrosis in many organ systems. Whether Endo-MT contributes to the pathogenesis of BPD is not known. We tested the hypothesis that pulmonary endothelial cells will show increased expression of Endo-MT markers upon exposure to hyperoxia and that sex as a biological variable will modulate differences in expression. WT and Cdh5-PAC CreERT2 (endothelial reporter) neonatal male and female mice (C57BL6) were exposed to hyperoxia (0.95 FiO2) either during the saccular stage of lung development (95% FiO2; PND1-5) or through the saccular and early alveolar stages of lung development (75% FiO2; PND1-14). Expression of Endo-MT markers were measured in whole lung and endothelial cell mRNA. Sorted lung endothelial cells were subjected to bulk RNA-Seq. We show that exposure of the neonatal lung to hyperoxia leads to upregulation of key markers of EndoMT Neonatal male mice show higher expression of genes related to EndoMT. Furthermore, using lung sc-RNAseq data from neonatal lung we were able to show that xxx. Markers related to Endo-MT are upregulated in the neonatal lung upon exposure to hyperoxia and show sex-specific differences. Mechanisms mediating EndoMT in the injured neonatal lung can modulate the response of the neonatal lung to hyperoxic injury and need further investigation.

2023-11-08 | GSE230672 | GEO

Microarray of neural progenitor cells from neonatal lung injury mice treated with placebo or umbilical-cord mesenchymal stromal cell extracellular vesicles or untreated, as well as age-matched control mice

Project description:The purpose of this experiment was to determine the transcriptional differences between neural progenitor cells from neonatal lung injury mice vs. control mice, as well as neonatal lung injury mice treated with umbilical-cord mesenchymal stromal cell extracellular vesicles vs. neonatal lung injury mice treated with placebo (PBS). Neural progenitor cells were isolated from the subventricular zone and hippocampus and cultured for 2 consecutive neurosphere assays. RNA was then extracted from the cells, and the microarray labelling, hybridization, and scanning was conducted by the Génome Québec Innovation Centre (Montréal, Canada).

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neonatal and adult mice lung

Project description:We performed miRNA array analysis from 4 groups (neonatal lung control, neonatal lung after hyperoxia, adult lung control, adult lung after hyperoxia). We used pools of every 100ng of total RNA of three samples for each groups.

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Three-axis classification of mouse lung mesenchymal cells reveals two populations of myofibroblasts

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Vessel Forming Mesenchymal Stromal Cell Populations

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RNA sequence of CD49f-positive mesenchymal populations in dermis of neonatal mice

Project description:We defined CD49f-high, CD49f-low and CD49f-neg mesenchymal subpopulations in the dermis. Transcriptome analysis revealed that CD49fhigh cells highly express gene regulatory network of neural crest cells, while CD49flow cells were enriched with melanocyte lineage development and maintenance related genes. The identity and function of above cell populations were further verified by lineage tracing.

2019-08-16 | GSE135471 | GEO

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