Epithelial marker genes are expressed in cultured embryonic rat lung and in vivo with similar spatial and temporal patterns.

Meneghetti, Alessandra; Cardoso, Wellington V.; Brody, Jerome S.; Williams, M.

doi:10.1177/44.10.8813083

Cited by 23 publications

(22 citation statements)

References 19 publications

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“…Among these are studies on lung embryos, which have illustrated coexpression of markers specific for both types I and II cells. 63,64 Resident putative 'stem cell' populations, such as the bronchi-alveolar stem cells, 17 have now been identified and have been shown to regenerate damaged epithelium. Importantly, there have been numerous studies implicating bone marrow-derived cells as an exogenous progenitor cell pool contributing to type I cell regeneration.…”

Section: Discussionmentioning

confidence: 99%

Identification of mesenchymal stromal cells in human lung parenchyma capable of differentiating into aquaporin 5-expressing cells

Karoubi

Cortes-Dericks

Breyer

et al. 2009

Laboratory Investigation

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The lack of effective therapies for end-stage lung disease validates the need for stem cell-based therapeutic approaches as alternative treatment options. In contrast with exogenous stem cell sources, the use of resident progenitor cells is advantageous considering the fact that the lung milieu is an ideal and familiar environment, thereby promoting the engraftment and differentiation of transplanted cells. Recent studies have shown the presence of multipotent 'mesenchymal stem cells' in the adult lung. The majority of these reports are, however, limited to animal models, and to date, there has been no report of a similar cell population in adult human lung parenchyma. Here, we show the identification of a population of primary human lung parenchyma (pHLP) mesenchymal stromal cells (MSCs) derived from intraoperative normal lung parenchyma biopsies. Surface and intracellular immunophenotyping by flow cytometry revealed that cultures do not contain alveolar type I epithelial cells or Clara cells, and are devoid of the following hematopoietic markers: CD34, CD45 and CXCR4. Cells show an expression pattern of surface antigens characteristic of MSCs, including CD73, CD166, CD105, CD90 and STRO-1. As per bone marrow MSCs, our pHLP cells have the ability to differentiate along the adipogenic, osteogenic and chondrogenic mesodermal lineages when cultured in the appropriate conditions. In addition, when placed in small airway growth media, pHLP cell cultures depict the expression of aquaporin 5 and Clara cell secretory protein, which is identified with that of alveolar type I epithelial cells and Clara cells, respectively, thereby exhibiting the capacity to potentially differentiate into airway epithelial cells. Further investigation of these resident cells may elucidate a therapeutic cell population capable of lung repair and/or regeneration.

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Section: Discussionmentioning

confidence: 99%

Identification of mesenchymal stromal cells in human lung parenchyma capable of differentiating into aquaporin 5-expressing cells

Karoubi

Cortes-Dericks

Breyer

et al. 2009

Laboratory Investigation

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“…In vivo by RT-PCR, we have detected the transcript for SP-C, but not CC10, in the endoderm by the 20-somite stage, 9.5 days gestation (data not shown); CC10 is first expressed in the developing rat lung at E14 by RT-PCR (Meneghetti et al, 1996). Similar to the proportion of explants positive for NKX2.1, we detected mRNA or protein for SP-C and CC10 in 18 out of 40 (45%) and in 10 of 22 (45%) ventral endoderm/cardiac mesoderm explants, respectively (Fig.…”

Section: Lung Specification Is Induced By Adjacent Cardiac Mesodermmentioning

confidence: 92%

Different thresholds of fibroblast growth factors pattern the ventral foregut into liver and lung

et al. 2005

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Cell fate and morphogenesis within the embryo is dependent upon secreted molecules that transduce signals between neighboring tissues. Reciprocal mesenchymal-epithelial interactions have proven essential during branching morphogenesis and cell differentiation within the lung; however, the interactions that result in lung specification from the foregut endoderm,prior to lung bud formation, are poorly understood. In this study, we investigate the tissue requirements and signals necessary for specification of a pulmonary cell fate using embryo tissue explants. We show that NKX2.1, an early transcription factor crucial for lung development, is expressed in the ventral foregut endoderm shortly after albumin and Pdx1, early markers of the liver and pancreas lineages, respectively. Similar to hepatic specification,direct contact of cardiac mesoderm with ventral endoderm is required to induce in vitro expression of NKX2.1 and downstream lung target genes including surfactant protein C and Clara cell secretory protein. In the absence of cardiac mesoderm, ventral foregut endoderm explants respond to exogenous fibroblast growth factor (FGF) 1 and FGF2 in a dose-dependent manner, with lower concentrations activating liver specific genes and higher concentrations activating lung specific genes. This signaling appears to be instructive, as the prospective dorsal midgut endoderm, which predominantly gives rise to the intestinal tract, is competent to respond to FGFs by inducing NKX2.1. Furthermore, the temporal expression and selective inhibition of FGF receptors 1 and 4 present within the endoderm implies that signaling through FGFR4 is involved in specifying lung versus liver. Together, the findings suggest that a concentration threshold of FGFs emanating from the cardiac mesoderm are involved in patterning the foregut endoderm.

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“…CCSP is expressed in Clara cells from approximately E16-E17 gestation. The CCSP-rtTA transgene is also active in a subset of type II cells after birth (41,63). Thus, in this CCSP-rtTA system for Cebp␣ ⌬/⌬ mice, deletion of Cebp␣ occurred in Clara cells from E16-E17 gestation and in subsets of type II cells after birth.…”

Section: Deletion Of Cebp␣ In Cebp␣mentioning

confidence: 92%

C/EBPα is required for pulmonary cytoprotection during hyperoxia

Xu¹,

Saegusa²,

Schehr³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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A number of transcriptional pathways regulating fetal lung development are active during repair of the injured lung. We hypothesized that C/EBPα, a transcription factor critical for lung maturation, plays a role in protection of the alveolar epithelium following hyperoxic injury of the mature lung. Transgenic CebpαΔ/Δmice, in which Cebpα was conditionally deleted from Clara cells and type II cells after birth, were developed. While no pulmonary abnormalities were observed in the CebpαΔ/Δmice (7–8 wk old) under normal conditions, the mice were highly susceptible to hyperoxia. CebpαΔ/Δmice died within 4 days of exposure to 95% oxygen in association with severe lung inflammation, altered maturation of surfactant protein B and C, decreased surfactant lipid secretion, and abnormal lung mechanics at a time when all control mice survived. mRNA microarray analysis of isolated type II cells at 0, 2, and 24 h of hyperoxia demonstrated the reduced expression of number of genes regulating surfactant lipid and protein homeostasis, including Srebf, Scap, Lpcat1, Abca3, Sftpb, and Napsa. Genes influencing cell signaling or immune responses were induced in the lungs of CebpαΔ/Δmice. C/EBPα was required for the regulation of genes associated with surfactant lipid homeostasis, surfactant protein biosynthesis, processing and transport, defense response to stress, and cell redox homeostasis during exposure to hyperoxia. While C/EBPα did not play a critical role in postnatal pulmonary function under normal conditions, C/EBPα mediated protection of the lung during acute lung injury induced by hyperoxia.

show abstract

Epithelial marker genes are expressed in cultured embryonic rat lung and in vivo with similar spatial and temporal patterns.

Cited by 23 publications

References 19 publications

Identification of mesenchymal stromal cells in human lung parenchyma capable of differentiating into aquaporin 5-expressing cells

Identification of mesenchymal stromal cells in human lung parenchyma capable of differentiating into aquaporin 5-expressing cells

Different thresholds of fibroblast growth factors pattern the ventral foregut into liver and lung

C/EBPα is required for pulmonary cytoprotection during hyperoxia

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