Single-Cell Transcriptomic Profiling Identifies Molecular Phenotypes of Newborn Human Lung Cells.

Bibliographic Details
Title: Single-Cell Transcriptomic Profiling Identifies Molecular Phenotypes of Newborn Human Lung Cells.
Authors: Bhattacharya, Soumyaroop, Myers, Jacquelyn A., Baker, Cameron, Guo, Minzhe, Danopoulos, Soula, Myers, Jason R., Bandyopadhyay, Gautam, Romas, Stephen T., Huyck, Heidie L., Misra, Ravi S., Dutra, Jennifer, Holden-Wiltse, Jeanne, McDavid, Andrew N., Ashton, John M., Al Alam, Denise, Potter, S. Steven, Whitsett, Jeffrey A., Xu, Yan, Pryhuber, Gloria S., Mariani, Thomas J.
Source: Genes; Mar2024, Vol. 15 Issue 3, p298, 20p
Subject Terms: LUNGS, HUMAN phenotype, TRANSCRIPTOMES, LUNG development, GENE mapping, SMOOTH muscle, FROZEN human embryos, KNOWLEDGE gap theory
Abstract: While animal model studies have extensively defined the mechanisms controlling cell diversity in the developing mammalian lung, there exists a significant knowledge gap with regards to late-stage human lung development. The NHLBI Molecular Atlas of Lung Development Program (LungMAP) seeks to fill this gap by creating a structural, cellular and molecular atlas of the human and mouse lung. Transcriptomic profiling at the single-cell level created a cellular atlas of newborn human lungs. Frozen single-cell isolates obtained from two newborn human lungs from the LungMAP Human Tissue Core Biorepository, were captured, and library preparation was completed on the Chromium 10X system. Data was analyzed in Seurat, and cellular annotation was performed using the ToppGene functional analysis tool. Transcriptional interrogation of 5500 newborn human lung cells identified distinct clusters representing multiple populations of epithelial, endothelial, fibroblasts, pericytes, smooth muscle, immune cells and their gene signatures. Computational integration of data from newborn human cells and with 32,000 cells from postnatal days 1 through 10 mouse lungs generated by the LungMAP Cincinnati Research Center facilitated the identification of distinct cellular lineages among all the major cell types. Integration of the newborn human and mouse cellular transcriptomes also demonstrated cell type-specific differences in maturation states of newborn human lung cells. Specifically, newborn human lung matrix fibroblasts could be separated into those representative of younger cells (n = 393), or older cells (n = 158). Cells with each molecular profile were spatially resolved within newborn human lung tissue. This is the first comprehensive molecular map of the cellular landscape of neonatal human lung, including biomarkers for cells at distinct states of maturity. [ABSTRACT FROM AUTHOR]
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  Data: Single-Cell Transcriptomic Profiling Identifies Molecular Phenotypes of Newborn Human Lung Cells.
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  Data: Genes; Mar2024, Vol. 15 Issue 3, p298, 20p
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  Data: <searchLink fieldCode="DE" term="%22LUNGS%22">LUNGS</searchLink><br /><searchLink fieldCode="DE" term="%22HUMAN+phenotype%22">HUMAN phenotype</searchLink><br /><searchLink fieldCode="DE" term="%22TRANSCRIPTOMES%22">TRANSCRIPTOMES</searchLink><br /><searchLink fieldCode="DE" term="%22LUNG+development%22">LUNG development</searchLink><br /><searchLink fieldCode="DE" term="%22GENE+mapping%22">GENE mapping</searchLink><br /><searchLink fieldCode="DE" term="%22SMOOTH+muscle%22">SMOOTH muscle</searchLink><br /><searchLink fieldCode="DE" term="%22FROZEN+human+embryos%22">FROZEN human embryos</searchLink><br /><searchLink fieldCode="DE" term="%22KNOWLEDGE+gap+theory%22">KNOWLEDGE gap theory</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: While animal model studies have extensively defined the mechanisms controlling cell diversity in the developing mammalian lung, there exists a significant knowledge gap with regards to late-stage human lung development. The NHLBI Molecular Atlas of Lung Development Program (LungMAP) seeks to fill this gap by creating a structural, cellular and molecular atlas of the human and mouse lung. Transcriptomic profiling at the single-cell level created a cellular atlas of newborn human lungs. Frozen single-cell isolates obtained from two newborn human lungs from the LungMAP Human Tissue Core Biorepository, were captured, and library preparation was completed on the Chromium 10X system. Data was analyzed in Seurat, and cellular annotation was performed using the ToppGene functional analysis tool. Transcriptional interrogation of 5500 newborn human lung cells identified distinct clusters representing multiple populations of epithelial, endothelial, fibroblasts, pericytes, smooth muscle, immune cells and their gene signatures. Computational integration of data from newborn human cells and with 32,000 cells from postnatal days 1 through 10 mouse lungs generated by the LungMAP Cincinnati Research Center facilitated the identification of distinct cellular lineages among all the major cell types. Integration of the newborn human and mouse cellular transcriptomes also demonstrated cell type-specific differences in maturation states of newborn human lung cells. Specifically, newborn human lung matrix fibroblasts could be separated into those representative of younger cells (n = 393), or older cells (n = 158). Cells with each molecular profile were spatially resolved within newborn human lung tissue. This is the first comprehensive molecular map of the cellular landscape of neonatal human lung, including biomarkers for cells at distinct states of maturity. [ABSTRACT FROM AUTHOR]
– Name: Abstract
  Label:
  Group: Ab
  Data: <i>Copyright of Genes is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.3390/genes15030298
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        Text: English
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      – SubjectFull: KNOWLEDGE gap theory
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      – TitleFull: Single-Cell Transcriptomic Profiling Identifies Molecular Phenotypes of Newborn Human Lung Cells.
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              Text: Mar2024
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