Airway stem cells sense hypoxia and differentiate into protective solitary neuroendocrine cells

Author:

Shivaraju Manjunatha123ORCID,Chitta Udbhav K.4,Grange Robert M. H.5ORCID,Jain Isha H.6789,Capen Diane10ORCID,Liao Lan11,Xu Jianming11ORCID,Ichinose Fumito5ORCID,Zapol Warren M.5ORCID,Mootha Vamsi K.678ORCID,Rajagopal Jayaraj123ORCID

Affiliation:

1. Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA.

2. Departments of Internal Medicine and Pediatrics, Pulmonary and Critical Care Division, Massachusetts General Hospital, Boston, MA 02114, USA,

3. Harvard Stem Cell Institute, Cambridge, MA 02138, USA.

4. Northeastern University, 360 Huntington Ave., Boston, MA 02115, USA.

5. Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.

6. Department of Molecular Biology and Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA, USA.

7. Department of Systems Biology, Harvard Medical School, Boston, MA, USA.

8. Broad Institute of Harvard and MIT, Cambridge, MA, USA.

9. Present address: Department of Physiology, University of California San Francisco, San Francisco, CA 94158, USA.

10. Program in Membrane Biology and Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

11. Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

Abstract

Protecting the lung from hypoxic stress The lung experiences constantly changing oxygen concentrations and must recognize and respond to a low-oxygen environment. Shivaraju et al. reveal that airway stem cells directly sense hypoxia and respond by differentiating into protective neuroendocrine (NE) cells that secrete a peptide that mitigates tissue damage (see the Perspective by Zacharias). This work suggests that the observed NE cell hyperplasia that accompanies lung diseases such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease represents a compensatory physiologic response. More broadly, it raises the possibility that stem cells throughout the body sense hypoxia and differentiate into organ-specific NE cells. Science , this issue p. 52 ; see also p. 32

Funder

mgh scholar

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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