肺多潜能上皮干细胞在肺损伤修复中的作用
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摘要
肺作为一个复杂的多功能器官,对人类生存至关重要。肺上皮细胞对维持肺脏功能和修复肺脏损伤具有重要作用。近年来研究认为,位于细支气管与肺泡交界处有一种肺干细胞,即支气管肺泡干细胞(bronchioalveolar stem cells, BASCs),但由于体内示踪BASCs的技术瓶颈,该干细胞是否具有再生为肺脏上皮细胞的能力一直存在争论。中国科学院生物化学与细胞生物学研究所周斌研究团队及其合作者的最新研究成果利用双同源重组系统(Cre-loxP和Dre-rox)特异性标记和示踪BASCs,并结合不同小鼠肺脏损伤模型揭示,BASCs在体内具有再生肺脏的能力,为肺脏的修复和再生研究提供了新的理论基础及研究方向。
As a complex multi-functional organ, the lung is vital to human survival. The lung epithelial stem cells are essential for lung function maintenance and lung regeneration. Recent studies have reported a unique stem cell population termed bronchioalveolar stem cells(BASCs) located at the bronchioalveolar-duct junctions.However, because of the lack of genetic tools to specifically label and track these putative BASCs, their potential roles in lung regeneration is not known. A recent study by Bin Zhou's research team and its collaborators from the Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences solved this technical problem by using dual homologous recombination systems(Cre-loxP and Dre-rox) to specifically label and trace BASCs.Combining this technique with different mouse lung injury models, fate-mapping result reveals the ability of BASCs to regenerate lungs in vivo. This study provides in vivo genetic evidence for the function of BASCs and also new insights into lung repair and regeneration.
As a complex multi-functional organ, the lung is vital to human survival. The lung epithelial stem cells are essential for lung function maintenance and lung regeneration. Recent studies have reported a unique stem cell population termed bronchioalveolar stem cells(BASCs) located at the bronchioalveolar-duct junctions.However, because of the lack of genetic tools to specifically label and track these putative BASCs, their potential roles in lung regeneration is not known. A recent study by Bin Zhou's research team and its collaborators from the Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences solved this technical problem by using dual homologous recombination systems(Cre-loxP and Dre-rox) to specifically label and trace BASCs.Combining this technique with different mouse lung injury models, fate-mapping result reveals the ability of BASCs to regenerate lungs in vivo. This study provides in vivo genetic evidence for the function of BASCs and also new insights into lung repair and regeneration.
引文
[1]Kuo CS,Krasnow MA.Formation of a neurosensory organ by epithelial cell slithering.Cell,2015,163(2):394-405
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[12]Zacharias WJ,Frank DB,Zepp JA,et al.Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor.Nature,2018,555(7695):251-255
[13]Nabhan AN,Brownfield DG,Harbury PB,et al.Singlecell Wnt signaling niches maintain stemness of alveolar type 2 cells.Science,2018,359(6380):1118-1123
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[15]Kim CF,Jackson EL,Woolfenden AE,et al.Identification of bronchioalveolar stem cells in normal lung and lung cancer.Cell,2005,121(6):823-835
[16]Giangreco A,Reynolds SD,Stripp BR.Terminal bronchioles harbor a unique airway stem cell population that localizes to the bronchoalveolar duct junction.Am JPathol,2002,161(1):173-182
[17]Dovey JS,Zacharek SJ,Kim CF,et al.Bmi1 is critical for lung tumorigenesis and bronchioalveolar stem cell expansion.Proc Natl Acad Sci USA,2008,105(33):11857-11862
[18]Nolen-Walston RD,Kim CF,Mazan MR,et al.Cellular kinetics and modeling of bronchioalveolar stem cell response during lung regeneration.Am J Physiol Lung Cell Mol Physiol,2008,294(6):L1158-L1165
[19]Zacharek SJ,Fillmore CM,Lau AN,et al.Lung stem cell self-renewal relies on BMI1-dependent control of expression at Imprinted Loci.Cell Stem Cell,2011,9(3):272-280
[20]Lee JH,Bhang DH,Beede A,et al.Lung stem cell differentiation in mice directed by endothelial cells via a BMP4-NFATc1-thrombospondin-1 axis.Cell,2014,156(3):440-455
[21]Barkauskas CE,Cronce MJ,Rackley CR,et al.Type 2alveolar cells are stem cells in adult lung.J Clin Invest,2013,123(7):3025-3036
[22]Tian X,Pu WT and Zhou B.Cellular origin and developmental program of coronary angiogenesis.Circ Res,2015,116(3):515-530
[23]Liu K,Yu W,Tang MX,et al.A dual genetic tracing system identifies diverse and dynamic origins of cardiac valve mesenchyme.Development,2018,145(18):dev167775
[2]Morrisey EE,Hogan BL.Preparing for the first breath:genetic and cellular mechanisms in lung edvelopment.Dev Cell,2010,18(1):8-23
[3]Rock JR,Hogan BL.Epithelial rogenitor ells in ung evelopment,aintenance,epair,and isease.Ann Rev Cell Dev Biol,2011,27:493-512
[4]Hong KU,Reynolds SD,Watkins S,et al.Basal cells are a multipotent progenitor capable of renewing the bronchial epithelium.Am J Pathol,2004,164(2):577-588
[5]Hong KU,Reynolds SD,Watkins S,et al.In vivo differentiation potential of tracheal basal cells:evidence for multipotent and unipotent subpopulations.Am J Physiol Lung Cell Mol Physiol,2004,286(4):L643-L649
[6]Rock JR,Onaitis MW,Rawlins EL,et al.Basal cells as stem cells of the mouse trachea and human airway epithelium.Proc Natl Acad Sci USA,2009,106(31):12771-12775
[7]Hong KU,Reynolds SD,Giangreco A,et al.Clara cell secretory protein-expressing cells of the airway neuroepithelial body microenvironment include a label-retaining subset and are critical for epithelial renewal after progenitor cell depletion.Am J Respir Cell Mol Biol,2001,24(6):671-681
[8]Rawlins EL,Okubo T,Xue Y,et al.The role of Scgb1a1+Clara cells in the long-term maintenance and repair of lung airway,but not alveolar,epithelium.Cell Stem Cell,2009,4(6):525-534
[9]Liu Q,Liu K,Cui G,et al.Lung regeneration by multipotent stem cells residing at the bronchioalveolar-duct junction.Nat Genet,2019,doi:10.1038/s41588-019-0346-6
[10]Desai TJ,Brownfield DG,Krasnow MA.Alveolar progenitor and stem cells in lung development,renewal and cancer.Nature,2014,507(7491):190-194
[11]Barkauskas CE,Cronce MJ,Rackley CR,et al.Type 2alveolar cells are stem cells in adult lung.J Clin Invest,2013,123(7):3025-3036
[12]Zacharias WJ,Frank DB,Zepp JA,et al.Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor.Nature,2018,555(7695):251-255
[13]Nabhan AN,Brownfield DG,Harbury PB,et al.Singlecell Wnt signaling niches maintain stemness of alveolar type 2 cells.Science,2018,359(6380):1118-1123
[14]Tata PR,Mou HM,Pardo-Saganta A,et al.Dedifferentiation of committed epithelial cells into stem cells in vivo.Nature,2013,503(7475):218-223
[15]Kim CF,Jackson EL,Woolfenden AE,et al.Identification of bronchioalveolar stem cells in normal lung and lung cancer.Cell,2005,121(6):823-835
[16]Giangreco A,Reynolds SD,Stripp BR.Terminal bronchioles harbor a unique airway stem cell population that localizes to the bronchoalveolar duct junction.Am JPathol,2002,161(1):173-182
[17]Dovey JS,Zacharek SJ,Kim CF,et al.Bmi1 is critical for lung tumorigenesis and bronchioalveolar stem cell expansion.Proc Natl Acad Sci USA,2008,105(33):11857-11862
[18]Nolen-Walston RD,Kim CF,Mazan MR,et al.Cellular kinetics and modeling of bronchioalveolar stem cell response during lung regeneration.Am J Physiol Lung Cell Mol Physiol,2008,294(6):L1158-L1165
[19]Zacharek SJ,Fillmore CM,Lau AN,et al.Lung stem cell self-renewal relies on BMI1-dependent control of expression at Imprinted Loci.Cell Stem Cell,2011,9(3):272-280
[20]Lee JH,Bhang DH,Beede A,et al.Lung stem cell differentiation in mice directed by endothelial cells via a BMP4-NFATc1-thrombospondin-1 axis.Cell,2014,156(3):440-455
[21]Barkauskas CE,Cronce MJ,Rackley CR,et al.Type 2alveolar cells are stem cells in adult lung.J Clin Invest,2013,123(7):3025-3036
[22]Tian X,Pu WT and Zhou B.Cellular origin and developmental program of coronary angiogenesis.Circ Res,2015,116(3):515-530
[23]Liu K,Yu W,Tang MX,et al.A dual genetic tracing system identifies diverse and dynamic origins of cardiac valve mesenchyme.Development,2018,145(18):dev167775
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