Mapping the dialogue: Decoding alveolar stem-niche interactions.

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Title: Mapping the dialogue: Decoding alveolar stem-niche interactions.
Authors: Nabhan, Ahmad N.1,2 nabhan@berkeley.edu, Biton, Anne3, Everett, Christine4, Foo, Conrad5, Wu, Diana4, Webster, Joshua D.5, Alam, Alina A.1, Penna, Elisa5, Rost, Sandra5, Rohatgi, Neha6, Reja, Rohit3, Tulpano, Ranel J.1, Xie, Shiqi4, Eidenschenk, Celine4, Newton, Kim2, Arron, Joseph R.7, Dixit, Vishva M.2 dixit@gene.com
Source: Proceedings of the National Academy of Sciences of the United States of America. 7/14/2026, Vol. 123 Issue 28, p1-10. 29p.
Subjects: Stem cell niches, Stem cells, Cell proliferation, Pulmonary fibrosis, RNA sequencing, Lung injuries, Immune response
Abstract: While cellular atlases have revealed remarkable phenotypic diversity, how cells navigate this landscape to influence tissue behavior remains poorly understood. We present an alveolosphere screening platform for investigating interactions between lung stem cells and their fibroblast niche. We assessed the role of 201 candidate genes in stem cells via imaging, then used chimeric RNAseq analysis for a transcriptome-wide understanding of cell-autonomous effects on stem cells and non-cell-autonomous effects on the niche. This phenome-transcriptome map uncovered cellular states and pathways regulating proliferation, metabolism, and immune signaling. Notably, stem cells influenced scar-forming and immune programs in fibroblasts. This injury response was dependent on stem cell identity; loss of Nkx2.1, encoding the transcription factor conferring lung epithelial identity, rewired stem cell-niche interactions and had a greater non-cell-autonomous effect than eliminating the cancer genes Trp53, Egfr, or Cdkn2b. Our study highlights how functional atlases complement the cellular diversity revealed by descriptive methods. [ABSTRACT FROM AUTHOR]
Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. 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. (Copyright applies to all Abstracts.)
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  Data: Mapping the dialogue: Decoding alveolar stem-niche interactions.
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  Data: <searchLink fieldCode="AR" term="%22Nabhan%2C+Ahmad+N%2E%22">Nabhan, Ahmad N.</searchLink><relatesTo>1,2</relatesTo><i> nabhan@berkeley.edu</i><br /><searchLink fieldCode="AR" term="%22Biton%2C+Anne%22">Biton, Anne</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Everett%2C+Christine%22">Everett, Christine</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Foo%2C+Conrad%22">Foo, Conrad</searchLink><relatesTo>5</relatesTo><br /><searchLink fieldCode="AR" term="%22Wu%2C+Diana%22">Wu, Diana</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Webster%2C+Joshua+D%2E%22">Webster, Joshua D.</searchLink><relatesTo>5</relatesTo><br /><searchLink fieldCode="AR" term="%22Alam%2C+Alina+A%2E%22">Alam, Alina A.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Penna%2C+Elisa%22">Penna, Elisa</searchLink><relatesTo>5</relatesTo><br /><searchLink fieldCode="AR" term="%22Rost%2C+Sandra%22">Rost, Sandra</searchLink><relatesTo>5</relatesTo><br /><searchLink fieldCode="AR" term="%22Rohatgi%2C+Neha%22">Rohatgi, Neha</searchLink><relatesTo>6</relatesTo><br /><searchLink fieldCode="AR" term="%22Reja%2C+Rohit%22">Reja, Rohit</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Tulpano%2C+Ranel+J%2E%22">Tulpano, Ranel J.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Xie%2C+Shiqi%22">Xie, Shiqi</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Eidenschenk%2C+Celine%22">Eidenschenk, Celine</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Newton%2C+Kim%22">Newton, Kim</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Arron%2C+Joseph+R%2E%22">Arron, Joseph R.</searchLink><relatesTo>7</relatesTo><br /><searchLink fieldCode="AR" term="%22Dixit%2C+Vishva+M%2E%22">Dixit, Vishva M.</searchLink><relatesTo>2</relatesTo><i> dixit@gene.com</i>
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  Data: <searchLink fieldCode="DE" term="%22Stem+cell+niches%22">Stem cell niches</searchLink><br /><searchLink fieldCode="DE" term="%22Stem+cells%22">Stem cells</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+proliferation%22">Cell proliferation</searchLink><br /><searchLink fieldCode="DE" term="%22Pulmonary+fibrosis%22">Pulmonary fibrosis</searchLink><br /><searchLink fieldCode="DE" term="%22RNA+sequencing%22">RNA sequencing</searchLink><br /><searchLink fieldCode="DE" term="%22Lung+injuries%22">Lung injuries</searchLink><br /><searchLink fieldCode="DE" term="%22Immune+response%22">Immune response</searchLink>
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  Label: Abstract
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  Data: While cellular atlases have revealed remarkable phenotypic diversity, how cells navigate this landscape to influence tissue behavior remains poorly understood. We present an alveolosphere screening platform for investigating interactions between lung stem cells and their fibroblast niche. We assessed the role of 201 candidate genes in stem cells via imaging, then used chimeric RNAseq analysis for a transcriptome-wide understanding of cell-autonomous effects on stem cells and non-cell-autonomous effects on the niche. This phenome-transcriptome map uncovered cellular states and pathways regulating proliferation, metabolism, and immune signaling. Notably, stem cells influenced scar-forming and immune programs in fibroblasts. This injury response was dependent on stem cell identity; loss of Nkx2.1, encoding the transcription factor conferring lung epithelial identity, rewired stem cell-niche interactions and had a greater non-cell-autonomous effect than eliminating the cancer genes Trp53, Egfr, or Cdkn2b. Our study highlights how functional atlases complement the cellular diversity revealed by descriptive methods. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. 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: 10.1073/pnas.2606113123
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        Text: English
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      – SubjectFull: Stem cell niches
        Type: general
      – SubjectFull: Stem cells
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      – SubjectFull: Cell proliferation
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      – SubjectFull: Pulmonary fibrosis
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      – SubjectFull: RNA sequencing
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      – SubjectFull: Lung injuries
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      – SubjectFull: Immune response
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      – TitleFull: Mapping the dialogue: Decoding alveolar stem-niche interactions.
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