Stem cell migration drives lung repair in living mice

作者全名:Chioccioli, Maurizio; Liu, Shuyu; Magruder, Sumner; Tata, Aleksandra; Borriello, Lucia; McDonough, John E.; Konkimalla, Arvind; Kim, Sang -Hun; Nouws, Jessica; Gonzalez, David G.; Traub, Brian; Ye, Xianjun; Yang, Tao; Entenberg, David R.; Krishnaswamy, Smita; Hendry, Caroline E.; Kaminski, Naftali; Tata, Purushothama Rao; Sauler, Maor

作者地址:[Chioccioli, Maurizio; Gonzalez, David G.; Krishnaswamy, Smita; Hendry, Caroline E.] Yale Univ, Dept Genet & Comparat Med, New Haven, CT 06519 USA; [Chioccioli, Maurizio] Yale Univ, Dept Comparat Med, New Haven, CT 06519 USA; [Liu, Shuyu; Tata, Aleksandra; Konkimalla, Arvind; Tata, Purushothama Rao] Duke Univ, Sch Med, Dept Cell Biol, Durham, NC 27710 USA; [Magruder, Sumner; Krishnaswamy, Smita] Yale Univ, Dept Comp Sci, New Haven, CT 06511 USA; [Borriello, Lucia] Lewis Katz Sch Med, Dept Canc & Cellular Biol, Fox Chase Canc, Philadelphia, PA 19140 USA; [McDonough, John E.] McMaster Univ, Fac Hlth Sci, Hamilton, ON L8S 4L8, Canada; [Konkimalla, Arvind] Duke Univ, Sch Med, Med Scientist Training Program, Durham, NC 27710 USA; [Kim, Sang -Hun; Nouws, Jessica; Sauler, Maor] Yale Sch Med, Pulm Crit Care & Sleep Med, New Haven, CT 06520 USA; [Traub, Brian; Ye, Xianjun; Entenberg, David R.] Albert Einstein Coll Med, Montefiore Med Ctr, Dept Pathol, Bronx, NY 10461 USA; [Yang, Tao] Chongqing Med Univ, Sect Thorac & Cardiovasc Surg, Affiliated Hosp 1, Chongqing 400010, Peoples R China

通信作者:Chioccioli, M (通讯作者),Yale Univ, Dept Genet & Comparat Med, New Haven, CT 06519 USA.; Chioccioli, M (通讯作者),Yale Univ, Dept Comparat Med, New Haven, CT 06519 USA.

来源:DEVELOPMENTAL CELL

ESI学科分类:MOLECULAR BIOLOGY & GENETICS

WOS号:WOS:001227124900001

JCR分区:Q1

影响因子:10.7

年份:2024

卷号:59

期号:7

开始页: 

结束页: 

文献类型:Article

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摘要:Tissue repair requires a highly coordinated cellular response to injury. In the lung, alveolar type 2 cells (AT2s) act as stem cells to replenish both themselves and alveolar type 1 cells (AT1s); however, the complex orchestration of stem cell activity after injury is poorly understood. Here, we establish longitudinal imaging of AT2s in murine intact tissues ex vivo and in vivo in order to track their dynamic behavior over time. We discover that a large fraction of AT2s become motile following injury and provide direct evidence for their migration between alveolar units. High -resolution morphokinetic mapping of AT2s further uncovers the emergence of distinct motile phenotypes. Inhibition of AT2 migration via genetic depletion of ArpC3 leads to impaired regeneration of AT2s and AT1s in vivo . Together, our results establish a requirement for stem cell migration between alveolar units and identify properties of stem cell motility at high cellular resolution.

基金机构:National Institutes of Health [NIH R01HL141852, R01HL127349, U01HL145567, U01HL122626, R01HL155948, R21HL161556, R01HL146557, R01HL160939, R01HL153375, F30HL143911]; Gruss-Lipper Bio-photonics Center; Integrated Imaging Program at Einstein College of Medicine [CA200561]

基金资助正文:We thank Dr. Valentina Greco and Dr. Kaelyn Sumigray (Yale Genetics) for thoughtful discussion and feedback. We thank Dr. Derek Toomre and Felix Rivera Molina (Yale Cell Biology Cellular Imaging using New Microscopy Ap-proaches, CINEMA LAB) for imaging equipment, technical support, and fruit-ful discussions. This work was supported by grants from the National Institutes of Health (NIH R01HL141852, R01HL127349, U01HL145567, and U01HL122626 to N.K.; R01HL155948 to M.S.; R21HL161556 to M.C; R01HL146557, R01HL160939, R01HL160939, and R01HL153375 to P.R.T.; and F30HL143911 to A.K. Support was provided by the Gruss-Lipper Bio-photonics Center and the Integrated Imaging Program at Einstein College of Medicine to D.R.E., X.Y., and L.B., and CA200561 to B.T.