Mesenchymal stromal cells from neonatal tracheal aspirates demonstrate a pattern of gene expression consistent with a lung origin
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE24583 | GEO | 2010/10/08
SECONDARY ACCESSION(S): PRJNA132487
REPOSITORIES: GEO
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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
Project description:We have previously isolated mesenchymal stromal cells (MSCs) from the tracheal aspirates of premature neonates with respiratory distress. Although 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 with cord blood MSCs, including the transcription factors Tbx2, Tbx3, Wnt5a, FoxF1, and Gli2, each of which has been associated with lung development. Compared with lung fibroblasts, 710 gene probe transcripts were differentially expressed by the lung MSCs, including IL-6 and IL-8/CXCL8. Differential chemokine expression was confirmed by protein analysis. 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. On the other hand, limiting dilution analysis showed that fetal lung fibroblasts form colonies at a significantly lower rate than MSCs, and fibroblasts failed to undergo differentiation along adipogenic, osteogenic, and chondrogenic lineages. In conclusion, MSCs isolated from neonatal tracheal aspirates demonstrate a pattern of lung-specific gene expression, are distinct from lung fibroblasts, and secrete pro-inflammatory cytokines.
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Project description:Extreme preterm infants are a growing population in neonatal intensive care units who carry a high mortality and morbidity. Multiple factors play a role in preterm birth, resulting in major impact on organogenesis leading to complications including bronchopulmonary dysplasia (BPD). The goal of this study was to identify biomarker signatures associated with prematurity and BPD. We analyzed miRNA and mRNA profiles in tracheal aspirates (TAs) from 51 infants receiving invasive mechanical ventilation. 25 infants were extremely preterm and diagnosed with BPD, and 26 were term babies receiving invasive mechanical ventilation for elective procedures. We found specific mRNA-miRNA signatures in TAs that may serve as biomarkers for BPD pathogenesis, a consequence of extreme prematurity.
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Project description:Recently, SSEA4+ mesenchymal progenitor cells have been described in stromal cultures, where IPF (but not normal) progenitor cells show pathological properties both in vitro and in vivo. The purpose of this study is to determine differences between mesenchymal progenitor cells sorted from stromal cultures derived from the lung biopsies of IPF patients showing a slow progressive versus rapid progressive decline of lung function as previously defined (Trujillo, G et al Science trans med 2010). Further, both groups were also compared to their normal lung counterparts as well as SSEA4- mesenchymal progeny.
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Project description:miRNA expression in tracheal aspirates
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Project description:In an experimental mouse model we showed that ceramides play a role in the pathogenesis of bronchopulmonary dysplasia (BPD) and are a potential target for therapeutic intervention. We investigated whether ceramides are detectable in tracheal aspirates (TAs) of preterm infants and differ between infants with or without BPD.Infants born ? 32 weeks of gestational age in need of mechanical ventilation in the first week of life were included. TAs were obtained directly after intubation and at day 1, 3, 5, 7, and 14. Ceramide concentrations were measured by tandem mass spectrometry. At 36 weeks postmenstrual age BPD was defined as having had ? 28 days supplemental oxygen.122 infants were included, of which 14 died and 41 developed BPD. All infants showed an increase in ceramides after the first day of intubation. The ceramide profile differed significantly between preterm infants who did and did not develop BPD. However, the ceramide profile had no additional predictive value for BPD development over GA at birth, birth weight and total days of mechanical ventilation.Ceramides are measurable in TAs of preterm born infants and may be an early marker for BPD development.
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Project description:Extreme preterm infants are a growing population in the neonatal intensive care unit. Multiple factors play a role in preterm birth, resulting in complications including severe bronchopulmonary dysplasia (sBPD) without or with and pulmonary hypertension (BPD-PH). The goal of this study was to identify biomarker signatures associated with sBPD and BPD-PH. We analyzed profiles in tracheal aspirates (TAs) from 46 extremely preterm infants receiving invasive mechanical ventilation (25 sBPD, 21 BPD-PH) . We found specific miRNA signatures in TAs that may serve as biomarkers for the two disease phenotypes.
2022-06-01 | GSE205138 | GEO
Project description:Primary epithelial cells isolated from fetal lungs of rat fetuses with or without lung hypoplasia induced by the administration of nitrofen to pregnant rats. Control group included epithelial cells from normal fetal lungs. Treatment with amniotic fluid stem cell derived extracellular vesicles or with mesenchymal stromal cell derived exosomes, RNA-seq of both cargos included.
2021-03-23 | E-MTAB-8921 | biostudies-arrayexpress
Project description:Bronchopulmonary dysplasia (BPD) is a form of chronic lung disease that develops in neonates as a consequence of preterm birth, arrested fetal lung development, and inflammation. The incidence of BPD remains on the rise as a result of increasing survival of extremely preterm infants. Severe BPD contributes to significant health care costs and is associated with prolonged hospitalizations, respiratory infections, and neurodevelopmental deficits. In this study, we aimed to detect novel biomarkers of BPD severity. We collected tracheal aspirates (TAs) from preterm babies with mild/moderate (n = 8) and severe (n = 17) BPD, and we profiled the expression of 1048 miRNAs using a PCR array. Associations with biological pathways were determined with the Ingenuity Pathway Analysis (IPA) software. We found 31 miRNAs differentially expressed between the two disease groups (2-fold change, false discovery rate (FDR) < 0.05). Of these, 4 miRNAs displayed significantly higher expression levels, and 27 miRNAs had significantly lower expression levels in the severe BPD group when compared to the mild/moderate BPD group. IPA identified cell signaling and inflammation pathways associated with miRNA signatures. We conclude that TAs of extremely premature infants contain miRNA signatures associated with severe BPD. These may serve as potential biomarkers of disease severity in infants with BPD.
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Project description:The non-hematopoietic cell fraction of the bone marrow (BM) is classically identified as CD45– Ter119– CD31– (herein referred to as triple-negative cells or TNCs). Although TNCs are believed to contain heterogeneous stromal cell populations, they remain poorly defined. Here we show, unexpectedly, that the vast majority of TNCs (~85%) have a hematopoietic rather than mesenchymal origin. Single cell RNA-sequencing reveals erythroid and lymphoid progenitor signatures among CD51– TNCs. When cultured with BM-derived stromal cells, Ly6D+ CD44+ CD51–TNCs give rise to B-lymphoid cells, whereas Ly6D–CD44+ CD51–TNCs generate erythroid cells. In addition, CD44+ CD51– TNCs contribute to repopulate B-lymphoid and erythroid cells after transplantation in mice. The CD44+ CD51– TNC population also expands during phenylhydrazine-induced acute hemolysis or in a model of sickle cell anemia. These findings thus uncover physiologically relevant, yet unappreciated, classes of stromal-associated CD45– hematopoietic progenitors.
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