Selected Publications

Hernandez BJ, Cain MP, Lynch AM, Flores JR, Tuvim MJ, Dickey BF, Chen J. Intermediary role of lung alveolar type 1 cells in epithelial repair upon Sendai virus infection. Am J Respir Cell Mol Biol. June 2022. PMID: 35679221. See editorial.

Image caption: Optical projection tomography images of mouse lungs immunostained for SOX2+ airways at baseline (top left), 9-day (top right) and 28-day (bottom row; optical section on the right) after Sendai virus infection, showing loss and then recovery of airway cells and their invasion into the alveolar region. Image courtesy of Jichao Chen.

Narvaez Del Pilar O, Gacha-Garay MJ, Chen J.  Three-axis classification of mouse lung mesenchymal cells reveals two populations of myofibroblasts. Development 149(6), March 2022. PMID: 35302583. See preLights.

Image caption: Genetic sparse cell labeling showing distinct morphology of mouse lung mesenchymal cells including pericytes (top row), alveolar myofibroblasts (second row), ductal myofibroblasts (third row), and distal interstitial cells (bottom row). Image courtesy of Odemaris Narvaez del Pilar.

Little DR, Lynch AM, Yan Y, Akiyama H, Kimura S, Chen J. Lung lineage transcription factor NKX2-1 epigenetically resolves opposing cell fates in vivo. Nat Commun. May 4, 12(1):2509, 2021. PMID: 33947861.

Image caption: En face view of mouse lung alveoli at postnatal day 6, showing that the lung lineage transcription factor NKX2-1 (green) is present in both alveolar type 1 cells (flat as outlined by E-Cadherin in violet) and type 2 cells (cuboidal and expressing LAMP3 in magenta) and is found to epigenetically regulate the two opposing cell fates in vivo. Image courtesy of Jichao Chen.

Vila Ellis L, Chen J. A cell-centric view of lung alveologenesis. Dev Dyn. ePub 11/9, 2020. PMID: 33169483.

Image caption: En face view of an alveolar island in a postnatal day 9 mouse lung, immunostained for the epithelium (AQP5 in green), capillaries (ICAM2 in red), alveolar myofibroblasts (SMA in grey), and Car4 endothelial cells (magenta). Image courtesy of Lisandra Vila Ellis and Jichao Chen.

Cain MP, Hernandez BJ, Chen J. Quantitative single-cell interactomes in normal and virus-infected mouse lungs. Dis Model Mech. ePub 5/27, 2020. PMID: 32461220.

Image caption: Section immunostaining of a mature mouse lung with an airway and a vessel in the center to show cells of the four lineages are intermixed and within a signaling distance. Airway and alveolar epithelial cell nuclei are genetically labelled with Rosa^Sun1GFP/+; Shh^Cre/+ and immunostained for GFP (green). Endothelial cell nuclei are marked by a transcription factor ERG (red). Immune cells are stained for a membrane marker CD45 (orange). DAPI-stained nuclei (blue) that are negative for the other markers show mesenchymal cells. Image courtesy of Margo Cain.

Gerner-Mauro KN, Akiyama H, Chen J. Redundant and additive functions of the four Lef/Tcf transcription factors in lung epithelial progenitors. Proc Natl Acad Sci U S A. ePub 5/15, 2020. PMID: 32414917.

Image caption: Optical projection images of embryonic day 15 mouse lungs upon pan-epithelial triple or quadruple deletion of the 4 Lef/Tcf paralogs, shown at the same scale. While triple mutants with functional TCF7 (green) or TCF7L1 (yellow) are normal, those with functional LEF1 (magenta) or TCF7L2 (red) are hypoplastic; the quadruple mutant (cyan) barely forms a lung. Image courtesy of Kamryn Gerner-Mauro.

Vila Ellis L, Cain MP, Hutchison V, Flodby P, Crandall ED, Borok Z, Zhou B, Ostrin EJ, Wythe JD, Chen J. Epithelial Vegfa specifies a distinct endothelial population in the mouse lung. Dev Cell. 52 (5):617-630.e6, 2020. PMID: 32059772. See editorial.

Image caption: Confocal projection image of genetically-labeled endothelial cells in a postnatal day 5 mouse lung, showing a newly identified endothelial cell type (Car4+) with elaborate net-like morphology (one cell near bottom; the concentrated red signal corresponds to the nucleus), in comparison to other conventional capillary endothelial cells (four cells above). Diagram inset shows Car4 endothelial cells have unique locations: separated from the gas-exchange alveolar type 1 cells by a limited basement membrane without intervening pericytes. Image courtesy of Jichao Chen.

Little DR, Gerner-Mauro KN, Flodby P, Crandall ED, Borok Z, Akiyama H, Kimura S, Ostrin EJ, Chen J. Transcriptional control of lung alveolar type 1 cell development and maintenance by NK homeobox 2-1 (cover article). Proc Natl Acad Sci U S A. 116 (41): 20545-20555, 2019. PMID: 31548395.

Image caption: Scanning electron micrograph of an alveolar type 1 (AT1) cell-specific Nkx2-1 mutant lung, showing shrunken AT1 cells with aberrant apical microvilli-like structures characteristic of the gastrointestinal epithelium. Danielle R. Little et al. found that developing and mature AT1 cells, which constitute most of the gas exchange surface in the lungs, lose defining molecular and cellular features in the absence of the transcription factor NK homeobox 2-1 (NKX2-1) and instead adopt gastrointestinal cell features. The results suggest that NKX2-1 expression is essential for differentiation and maintenance of AT1 cells. Image courtesy of Danielle R. Little and Kenneth Dunner Jr.

Ostrin EJ, Little DR, Gerner-Mauro KN, Sumner EA, Ríos-Corzo R, Ambrosio E, Holt SE, Forcioli-Conti NR, Akiyama H, Hanash SM, Kimura S, Huang SXL, Chen J. Beta-Catenin maintains lung epithelial progenitors after lung specification (cover article). Development 145 (5), 2018. PMID: 29440304.

Image caption: A 3D-printed epithelial tree of an embryonic day 14.5 mouse lung showing thousands of branches formed by the epithelial progenitors within 4 days of development. Image courtesy of Kamryn Gerner-Mauro and Jichao Chen.

Yang J, Hernandez BJ, Martinez Alanis D, Narvaez Del Pilar O, Vila-Ellis L, Akiyama H, Evans SE, Ostrin EJ, Chen J. Development and Plasticity of Alveolar Type 1 Cells (cover article). Development 143 (1) :54-65, 2016. PMID: 26586225.

Image caption: Three-dimensional rendering of a confocal image stack showing a single alveolar type 1 cell with expansive cellular extensions (green, GFP, genetically labelled with Hopx^CreER/+; Rosa^mTmG/+) intertwined with the vasculature (blue, ICAM2) in the mouse lung. Image courtesy of Jichao Chen.

Yang J, Chen J. Developmental Programs of Lung Epithelial Progenitors: a Balanced Progenitor Model. Wiley Interdiscip Rev Dev Biol 3 (5) :331-47, 2014. PMID: 25124755.

Image caption: Optical projection image of an embryonic day 9.5 mouse embryo (posing as Rodin's Thinker) immunostained for E-Cadherin, showing budding of lung primordia from the ventral foregut. Image courtesy of Jichao Chen.

Alanis DM, Chang DR, Akiyama H, Krasnow MA, Chen J. Two Nested Developmental Waves Demarcate a Compartment Boundary in the Mouse Lung. Nat Commun 5:3923, 2014. PMID: 24879355.

Image caption: Optical projection tomography images of an embryonic day 16.5 mouse lung immunostained for SOX9 (green) epithelial progenitors and their SOX2 (magenta) progeny. Image courtesy of Jichao Chen.

Chang DR, Martinez Alanis D, Miller RK, Ji H, Akiyama H, McCrea PD, Chen J. Lung epithelial branching program antagonizes alveolar differentiation (cover article). Proc Natl Acad Sci U S A. 110 (45): 18042-51, 2013. PMID: 24058167. See editorial.

Image caption: An embryonic mouse lung undergoing a developmental process called branching morphogenesis, which builds a tree-like tubular network. E-cadherin, a protein expressed in the epithelium, is shown in blue, and Sox9, a protein expressed in branching tips and cartilage rings, is shown in yellow. Daniel Chang et al. found that branching morphogenesis antagonizes a second developmental process known as alveolar differentiation, which generates specialized epithelial cells for gas exchange. The findings reveal a previously unappreciated link between branching morphogenesis and alveolar differentiation in lung development. Image courtesy of Jichao Chen.