Person:
Paschini, Margherita

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Paschini

First Name

Margherita

Name

Paschini, Margherita
Author's Publications: search.filters.isAuthorOfPublication.c88d097c-3c2c-4447-86de-ce6df165d652

Search Results

Now showing 1 - 3 of 3
  • Thumbnail Image
    Publication
    Anatomically and Functionally Distinct Lung Mesenchymal Populations Marked by Lgr5 and Lgr6
    (Cell Press, 2017) Lee, Joo-Hyeon; Tammela, Tuomas; Hofree, Matan; Choi, Jinwook; Marjanovic, Nemanja Despot; Han, Seungmin; Canner, David; Wu, Katherine; Paschini, Margherita; Bhang, Dong Ha; Jacks, Tyler; Regev, Aviv; Kim, Carla
    Summary The diversity of mesenchymal cell types in the lung that influence epithelial homeostasis and regeneration is poorly defined. We used genetic lineage tracing, single-cell RNA sequencing, and organoid culture approaches to show that Lgr5 and Lgr6, well-known markers of stem cells in epithelial tissues, are markers of mesenchymal cells in the adult lung. Lgr6+ cells comprise a subpopulation of smooth muscle cells surrounding airway epithelia and promote airway differentiation of epithelial progenitors via Wnt-Fgf10 cooperation. Genetic ablation of Lgr6+ cells impairs airway injury repair in vivo. Distinct Lgr5+ cells are located in alveolar compartments and are sufficient to promote alveolar differentiation of epithelial progenitors through Wnt activation. Modulating Wnt activity altered differentiation outcomes specified by mesenchymal cells. This identification of region- and lineage-specific crosstalk between epithelium and their neighboring mesenchymal partners provides new understanding of how different cell types are maintained in the adult lung.
  • Thumbnail Image
    Publication
    Lkb1 inactivation drives lung cancer lineage switching governed by Polycomb Repressive Complex 2
    (Nature Publishing Group, 2017) Zhang, Haikuo; Fillmore Brainson, Christine; Koyama, Shohei; Redig, Amanda J; Chen, Ting; Li, Shuai; Gupta, Manav; Garcia-de-Alba, Carolina; Paschini, Margherita; Herter-Sprie, Grit S.; Lu, Gang; Zhang, Xin; Marsh, Bryan P.; Tuminello, Stephanie J.; Xu, Chunxiao; Chen, Zhao; Wang, Xiaoen; Akbay, Esra A.; Zheng, Mei; Palakurthi, Sangeetha; Sholl, Lynette; Rustgi, Anil K.; Kwiatkowski, David; Diehl, J Alan; Bass, Adam; Sharpless, Norman E.; Dranoff, Glenn; Hammerman, Peter S.; Ji, Hongbin; Bardeesy, Nabeel; Saur, Dieter; Watanabe, Hideo; Kim, Carla; Wong, Kwok-Kin
    Adenosquamous lung tumours, which are extremely poor prognosis, may result from cellular plasticity. Here, we demonstrate lineage switching of KRAS+ lung adenocarcinomas (ADC) to squamous cell carcinoma (SCC) through deletion of Lkb1 (Stk11) in autochthonous and transplant models. Chromatin analysis reveals loss of H3K27me3 and gain of H3K27ac and H3K4me3 at squamous lineage genes, including Sox2, ΔNp63 and Ngfr. SCC lesions have higher levels of the H3K27 methyltransferase EZH2 than the ADC lesions, but there is a clear lack of the essential Polycomb Repressive Complex 2 (PRC2) subunit EED in the SCC lesions. The pattern of high EZH2, but low H3K27me3 mark, is also prevalent in human lung SCC and SCC regions within ADSCC tumours. Using FACS-isolated populations, we demonstrate that bronchioalveolar stem cells and club cells are the likely cells-of-origin for SCC transitioned tumours. These findings shed light on the epigenetics and cellular origins of lineage-specific lung tumours.
  • No Thumbnail Available
    Publication
    Erratum: Lkb1 inactivation drives lung cancer lineage switching governed by Polycomb Repressive Complex 2
    (Springer Science and Business Media LLC, 2017-06-09) Zhang, Haikuo; Brainson, Christine Fillmore; Koyama, Shohei; Redig, Amanda J.; Chen, Ting; Li, Shuai; Gupta, Manav; Garcia-de-Alba, Carolina; Paschini, Margherita; Herter-Sprie, Grit S.; Lu, Gang; Zhang, Xin; Marsh, Bryan P; Tuminello, Stephanie J.; Xu, Chunxiao; Chen, Zhao; Wang, Xiaoen; Akbay, Esra A.; Zheng, Mei; Palakurthi, Sangeetha; Sholl, Lynette; Rustgi, Anil K.; Kwiatkowski, David; Diehl, J. Alan; Bass, Adam; Sharpless, Norman E.; Dranoff, Glenn; Hammerman, Peter S.; Ji, Hongbin; Bardeesy, Nabeel; Saur, Dieter; Watanabe, Hideo; Kim, Carla; Wong, Kwok-Kin