The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Prospective isolation of NKX2-1–expressing human lung progenitors derived from pluripotent stem cells
Open accessAbstract
It has been postulated that during human fetal development, all cells of the lung epithelium derive from embryonic, endodermal, NK2 homeobox 1-expressing (NKX2-1+) precursor cells. However, this hypothesis has not been formally tested owing to an inability to purify or track these progenitors for detailed characterization. Here we have engineered and developmentally differentiated NKX2-1GFP reporter pluripotent stem cells (PSCs) in vitro to generate and isolate human primordial lung progenitors that express NKX2-1 but are initially devoid of differentiated lung lineage markers. After sorting to purity, these primordial lung progenitors exhibited lung epithelial maturation. In the absence of mesenchymal coculture support, this NKX2-1+ population was able to generate epithelial-only spheroids in defined 3D cultures. Alternatively, when recombined with fetal mouse lung mesenchyme, the cells recapitulated epithelial-mesenchymal developing lung interactions. We imaged these progenitors in real time and performed time-series global transcriptomic profiling and single-cell RNA sequencing as they moved through the earliest moments of lung lineage specification. The profiles indicated that evolutionarily conserved, stage-dependent gene signatures of early lung development are expressed in primordial human lung progenitors and revealed a CD47hiCD26lo cell surface phenotype that allows their prospective isolation from untargeted, patient-specific PSCs for further in vitro differentiation and future applications in regenerative medicine.
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Single-cell transcriptomics reveals bimodality in expression and splicing in immune cells
Shalek, A. K., Satija, R., Adiconis, X., Gertner, R. S., Gaublomme, J. T., Raychowdhury, R., Schwartz, S., Yosef, N., Malboeuf, C., Lu, D., et al. (2013) · Nature · doi:10.1038/nature12172 · Cited by 1,190
Barclay, A. N., & van den Berg, T. K. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120142 · Cited by 841
Vertebrate Endoderm Development and Organ Formation
Zorn, A. M., & Wells, J. M. (2009) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.042308.113344 · Cited by 812
Epithelial-Mesenchymal Interactions in the Developing Lung
Shannon, J. M., & Hyatt, B. A. (2004) · Annual Review of Physiology · doi:10.1146/annurev.physiol.66.032102.135749 · Cited by 321
Self-citationTranscriptional dynamics of endodermal organ formation
Sherwood, R. I., Chen, T. A., & Melton, D. A. (2009) · Developmental Dynamics · doi:10.1002/dvdy.21810 · Cited by 191
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Metadata
- Authors
- Hawkins, F., Kramer, P., Jacob, A., Driver, I., Thomas, D. C., McCauley, K. B., Skvir, N., Crane, A. M., Kurmann, A. A., Hollenberg, A. N., Nguyen, S., Wong, B. G., Khalil, A. S., Huang, S. X. L., Guttentag, S., Rock, J. R., Shannon, J. M., Davis, B. R., & Kotton, D. N.
- Venue
- Journal of Clinical Investigation
- Published
- 2017-05-02
- Volume
- 127
- Issue
- 6
- Pages
- 2277-2294
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- OpenAlex
- W2611660641
- Cited by
- 239
- References
- 6
- FWCI
- 7.09
- Type
- journal article
- Language
- en
- Open access
- green
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- Hawkins, F., Kramer, P., Jacob, A., Driver, I., Thomas, D. C., McCauley, K. B., Skvir, N., Crane, A. M., Kurmann, A. A., Hollenberg, A. N., Nguyen, S., Wong, B. G., Khalil, A. S., Huang, S. X. L., Guttentag, S., Rock, J. R., Shannon, J. M., Davis, B. R., & Kotton, D. N. (2017). Prospective isolation of NKX2-1–expressing human lung progenitors derived from pluripotent stem cells. Journal of Clinical Investigation. https://doi.org/10.1172/jci89950
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