Lung regeneration by multipotent stem cells residing at the bronchioalveolar-duct junction

Qiaozhen Liu^#^{1

2}, Kuo Liu^#¹, Guizhong Cui^#¹, Xiuzhen Huang^{1

2}, Shun Yao¹, Wenke Guo^{1

3}, Zhen Qin¹, Yan Li^{1

2}, Rui Yang^{1

2}, Wenjuan Pu^{1

2}, Libo Zhang¹, Lingjuan He^{1

2}, Huan Zhao^{1

2}, Wei Yu^{1

2}, Muxue Tang^{1

4}, Xueying Tian⁵, Dongqing Cai⁵, Yu Nie⁶, Shengshou Hu⁶, Tao Ren⁷, Zengyong Qiao⁸, Hefeng Huang⁹, Yi Arial Zeng¹, Naihe Jing^{1

3}, Guangdun Peng^{10

11

12

13}, Hongbin Ji^{14

15}, Bin Zhou^{16

17

18

19

20

21}

Affiliations

¹ The State Key Laboratory of Cell Biology, CAS Center for Excellence on Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
² Institute of Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
³ School of Life Science and Technology, Shanghai Tech University, Shanghai, China.
⁴ School of Life Sciences, East China Normal University, Shanghai, China.
⁵ Key Laboratory of Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, China.
⁶ State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁷ Department of Respiratory Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
⁸ Department of Cardiovascular Medicine, Southern Medical University Affiliated Fengxian Hospital, Shanghai, China.
⁹ The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
¹⁰ The State Key Laboratory of Cell Biology, CAS Center for Excellence on Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. peng_guangdun@gibh.ac.cn.
¹¹ CAS Key Laboratory of Regenerative Biology and Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. peng_guangdun@gibh.ac.cn.
¹² Guangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), Guangzhou, China. peng_guangdun@gibh.ac.cn.
¹³ Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China. peng_guangdun@gibh.ac.cn.
¹⁴ The State Key Laboratory of Cell Biology, CAS Center for Excellence on Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. hbji@sibcb.ac.cn.
¹⁵ School of Life Science and Technology, Shanghai Tech University, Shanghai, China. hbji@sibcb.ac.cn.
¹⁶ The State Key Laboratory of Cell Biology, CAS Center for Excellence on Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. zhoubin@sibs.ac.cn.
¹⁷ Institute of Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. zhoubin@sibs.ac.cn.
¹⁸ School of Life Science and Technology, Shanghai Tech University, Shanghai, China. zhoubin@sibs.ac.cn.
¹⁹ Key Laboratory of Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, China. zhoubin@sibs.ac.cn.
²⁰ Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China. zhoubin@sibs.ac.cn.
²¹ Collaborative Innovation Center For Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China. zhoubin@sibs.ac.cn.

^# Contributed equally.

PMID: 30778223
DOI: 10.1038/s41588-019-0346-6

Lung regeneration by multipotent stem cells residing at the bronchioalveolar-duct junction

Qiaozhen Liu et al. Nat Genet. 2019 Apr.

. 2019 Apr;51(4):728-738.

doi: 10.1038/s41588-019-0346-6. Epub 2019 Feb 18.

Authors

Affiliations

¹ The State Key Laboratory of Cell Biology, CAS Center for Excellence on Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
² Institute of Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
³ School of Life Science and Technology, Shanghai Tech University, Shanghai, China.
⁴ School of Life Sciences, East China Normal University, Shanghai, China.
⁵ Key Laboratory of Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, China.
⁶ State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁷ Department of Respiratory Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
⁸ Department of Cardiovascular Medicine, Southern Medical University Affiliated Fengxian Hospital, Shanghai, China.
⁹ The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
¹⁰ The State Key Laboratory of Cell Biology, CAS Center for Excellence on Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. peng_guangdun@gibh.ac.cn.
¹¹ CAS Key Laboratory of Regenerative Biology and Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. peng_guangdun@gibh.ac.cn.
¹² Guangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), Guangzhou, China. peng_guangdun@gibh.ac.cn.
¹³ Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China. peng_guangdun@gibh.ac.cn.
¹⁴ The State Key Laboratory of Cell Biology, CAS Center for Excellence on Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. hbji@sibcb.ac.cn.
¹⁵ School of Life Science and Technology, Shanghai Tech University, Shanghai, China. hbji@sibcb.ac.cn.
¹⁶ The State Key Laboratory of Cell Biology, CAS Center for Excellence on Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. zhoubin@sibs.ac.cn.
¹⁷ Institute of Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. zhoubin@sibs.ac.cn.
¹⁸ School of Life Science and Technology, Shanghai Tech University, Shanghai, China. zhoubin@sibs.ac.cn.
¹⁹ Key Laboratory of Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, China. zhoubin@sibs.ac.cn.
²⁰ Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China. zhoubin@sibs.ac.cn.
²¹ Collaborative Innovation Center For Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China. zhoubin@sibs.ac.cn.

^# Contributed equally.

PMID: 30778223
DOI: 10.1038/s41588-019-0346-6

Erratum in

Author Correction: Lung regeneration by multipotent stem cells residing at the bronchioalveolar-duct junction.
Liu Q, Liu K, Cui G, Huang X, Yao S, Guo W, Qin Z, Li Y, Yang R, Pu W, Zhang L, He L, Zhao H, Yu W, Tang M, Tian X, Cai D, Nie Y, Hu S, Ren T, Qiao Z, Huang H, Zeng YA, Jing N, Peng G, Ji H, Zhou B. Liu Q, et al. Nat Genet. 2019 Apr;51(4):766. doi: 10.1038/s41588-019-0388-9. Nat Genet. 2019. PMID: 30846878

Abstract

Characterizing the stem cells responsible for lung repair and regeneration is important for the treatment of pulmonary diseases. Recently, a unique cell population located at the bronchioalveolar-duct junctions has been proposed to comprise endogenous stem cells for lung regeneration. However, the role of bronchioalveolar stem cells (BASCs) in vivo remains debated, and the contribution of such cells to lung regeneration is not known. Here we generated a genetic lineage-tracing system that uses dual recombinases (Cre and Dre) to specifically track BASCs in vivo. Fate-mapping and clonal analysis showed that BASCs became activated and responded distinctly to different lung injuries, and differentiated into multiple cell lineages including club cells, ciliated cells, and alveolar type 1 and type 2 cells for lung regeneration. This study provides in vivo genetic evidence that BASCs are bona fide lung epithelial stem cells with deployment of multipotency and self-renewal during lung repair and regeneration.

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References

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Lung regeneration by multipotent stem cells residing at the bronchioalveolar-duct junction

Affiliations

Lung regeneration by multipotent stem cells residing at the bronchioalveolar-duct junction

Authors

Affiliations

Erratum in

Abstract

References

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LinkOut - more resources

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