Dr. Tushar Desai specializes clinically in the treatment of general pulmonary and Interstitial Lung Diseases like Idiopathic Pulmonary Fibrosis (IPF). He has practiced pulmonary medicine since 2002.
Dr. Desai conducts basic and translational research on lung stem cells that repair and regenerate the lung after injury, and their role in diseases like IPF, Chronic Obstructive Pulmonary Disease (COPD), and lung adenocarcinoma. His lab also studies the molecular signals that regulate lung stem cell activity, and how the signals can be manipulated to restore their activity. He participates in research involving gene correction of CFTR in lung stem cells from patients with Cystic fibrosis followed by autologous stem cell transplantation to provide lifelong restoration of physiological activity.
- Pulmonary Disease
- Interstitial Lung Diseases
Member, Cardiovascular Institute
Member, Stanford Cancer Institute
Director of Graduate Studies, Stem Cell Biology PhD program (2021 - Present)
Director of Translational Lung Biology, Department of Medicine (2020 - Present)
Honors & Awards
Robert A. and Gertrude T. Hudson Endowed Professor, Stanford University School of Medicine (2020)
Elected Member, American Society for Clinical Investigation (2019)
Lung Force Gala Honoree, American Lung Association (2018)
Woods Family Endowed Faculty Scholar in Pediatric Translational Medicine, Stanford Child Health Research Institute (2016-2021)
Stanford Medical Student Teaching Recognition, Stanford University School of Medicine (2011-2014)
Robert Dawson Evans Fellow Excellence in Teaching Award, Boston University School of Medicine, Department of Internal Medicine (2000)
House Officer Research Award, University of Michigan Hospitals, Department of Internal Medicine (1998)
Worth F. Bloom M25 Prize, Tufts University School of Medicine (1995)
Boards, Advisory Committees, Professional Organizations
Member, American Society for Clinical Investigation (2019 - Present)
Member, Scientific Advisory Board, UK Regenerative Medicine Platform, Engineered Cell Environment Hub (2018 - Present)
Member, Scientific Advisory Committee, American Thoracic Society (ATS) (2015 - Present)
Fellowship: Boston University Pulmonary and Critical Care Fellowship (2002) MA
Residency: University of Michigan Health System Internal Medicine Residency (1998) MI
MD, MPH, Tufts University School of Medicine (1995)
BA, Amherst College, Psychology (1991)
Dawn T. Bravo, Sriram Vaidyanathan, Matthew H. Porteus, Calvin J. Kuo, Jayakar Nayak, Ameen Salahudeen and Tushar J. Desai. "United States Patent 17/353,049 Compositions and methods for airway tissue regeneration", Leland Stanford Junior University, Jun 21, 2021
Tushar Desai, Pehr Harbury, Daniel Riordan. "United States Patent 62/475,090 Molecular profiling using proximity ligation- in situ hybridization", Leland Stanford Junior University, Mar 22, 2017
Current Research and Scholarly Interests
My lab is focused on understanding the causes of and working towards specific molecular and cell-based treatments for lung diseases like cancer, pulmonary fibrosis, COPD. We focus our attention on lung stem cells and the molecular signals that regulate their activity to repair and regenerate lung tissue after injury. These same stem cells can become dysfunctional, generating cancer if they become overactive, and resulting in respiratory failure if they lose their potency. We are focused on Wnt signaling because this appears to be a key signal that confers stem cell potency in both mouse and human lung, and is overactive in diseases like lung adenocarcinoma and Idiopathic Pulmonary Fibrosis (IPF). My lab also studies the role of TERT in lung stem cell biology and repair of acute lung injury, which is a culprit gene mutation in IPF. Our experimental approaches involve mouse genetics, single cell genomics, organoid culture, lung slice culture, and we perform histological analysis of lung tissue using advanced fluorescence microscopy technologies. A portion of my lab is also involved in the invention of new technologies to facilitate highly multiplexed staining of protein (immunostaining) and RNA (in situ hybridization) of human tissues.
Lung stem cells can also be exploited to treat monogenic diseases, by using CRISPR to correct the genetic mutation then transplanting them back into the patient. This strategy of ex vivo gene correction in stem cells followed by autologous stem cell transplantation is already being trialed in blood disorders like Sickle cell anemia. We are part of a Stanford group that is using CRISPR to correct CFTR mutations in airway stem cells and working towards developing a protocol for safe and effective autologous transplantation into the sinuses of Cystic fibrosis patients. We hope to advance this cell-based therapeutic approach of transplanting stem cells into the airways and gas exchange region of the lungs to treat diseases resulting from loss of stem cell potency.
Detection of Integrin avb6 in IPF, PSC, and COVID19 Using PET/CT
Detection of Integrin avb6 in Idiopathic Pulmonary Fibrosis, Primary Sclerosing Cholangitis, and Coronavirus Disease 2019 with [18F]FP-R01-MG-F2 with PET/CT
- Stem Cell Intensive
STEMREM 200 (Aut)
- Stem Cells Immersion: Applications in Medicine, Business and Law
STEMREM 203 (Aut, Win)
Independent Studies (6)
- Directed Reading in Medicine
MED 299 (Aut, Win, Spr, Sum)
- Early Clinical Experience in Medicine
MED 280 (Aut, Win, Spr, Sum)
- Graduate Research
MED 399 (Aut, Win, Spr, Sum)
- Graduate Research
STEMREM 399 (Aut, Win, Spr, Sum)
- Medical Scholars Research
MED 370 (Aut, Win, Spr, Sum)
- Undergraduate Research
MED 199 (Aut, Win, Spr, Sum)
- Directed Reading in Medicine
Med Scholar Project Advisor
Joshua Guild, Marina Martinez
Doctoral Dissertation Reader (AC)
Shannon Choi, Katarina Klett
Postdoctoral Faculty Sponsor
Nicholas Juul, Ian Stancil, Jung Ki Yoon
Doctoral Dissertation Advisor (AC)
Joshua Guild, Courtney Stockman
Laura Amaya, Alvaro Amorin, Jessica Arozqueta Basurto, Khristian Bauer-Rowe, Jeremy Bjelajac, Quenton Bubb, Andrew Burden, Carsten Charlesworth, Lori Dershowitz, Sarah DiIorio, Carolyn Dundes, William Feist, Franco Felix, Jonas Fowler, Francisco Galdos, Hana Ghanim, Karen Gonzalez, Malachia Hoover, Nicole Horsley, Austin Huang, Omair Khan, Lauren Koepke, Ishan Kumar, John Lu, Shamik Mascharak, Jeeyoon Na, Jennifer Parker, Kenisha Puckett, Suyash Raj, Joshua Rico, Julien Roth, Julie Sanchez, Archana Shankar, Aaron Tan, Sicong Wang, Maya Weigel, Sarah Wilson
Postdoctoral Research Mentor
Nicholas Juul, Jung Ki Yoon
Graduate and Fellowship Programs
Pulmonary & Critical Care Medicine (Fellowship Program)
Alveolar cell fate selection and lifelong maintenance of AT2 cells by FGF signaling.
2022; 13 (1): 7137
The lung's gas exchange surface is comprised of alveolar AT1 and AT2 cells that are corrupted in several common and deadly diseases. They arise from a bipotent progenitor whose differentiation is thought to be dictated by differential mechanical forces. Here we show the critical determinant is FGF signaling. Fgfr2 is expressed in the developing progenitors in mouse then restricts to nascent AT2 cells and remains on throughout life. Its ligands are expressed in surrounding mesenchyme and can, in the absence of exogenous mechanical cues, induce progenitors to form alveolospheres with intermingled AT2 and AT1cells. FGF signaling directly and cell autonomously specifies AT2 fate; progenitors lacking Fgfr2 in vitro and in vivo exclusively acquire AT1 fate. Fgfr2 loss in AT2 cells perinatally results in reprogramming to AT1 identity, whereas loss or inhibition later in life triggers AT2 apoptosis and compensatory regeneration. We propose that Fgfr2 signaling selects AT2 fate during development, induces a cell non-autonomous AT1 differentiation signal, then continuously maintains AT2 identity and survival throughout life.
View details for DOI 10.1038/s41467-022-34059-1
View details for PubMedID 36414616
Developmental Insights into Lung Cancer
ANNUAL REVIEW OF CANCER BIOLOGY, VOL 5, 2021
2021; 5: 351–69
View details for DOI 10.1146/annurev-cancerbio-070820-032858
View details for Web of Science ID 000627716400019
- Lung stem cells and therapy for cystic fibrosis Lung Stem Cells in Development, Health and Disease (ERS Monograph) edited by Nikolic, M. Z., Hogan, B. L. 2021: 306-321
Progenitor identification and SARS-CoV-2 infection in human distal lung organoids.
The distal lung contains terminal bronchioles and alveoli that facilitate gas exchange. Three-dimensional in vitro human distal lung culture systems would strongly facilitate investigation of pathologies including interstitial lung disease, cancer, and SARS-CoV-2-associated COVID-19 pneumonia. We generated long-term feeder-free, chemically defined culture of distal lung progenitors as organoids derived from single adult human alveolar epithelial type II (AT2) or KRT5+ basal cells. AT2 organoids exhibited AT1 transdifferentiation potential while basal cell organoids developed lumens lined by differentiated club and ciliated cells. Single cell analysis of basal organoid KRT5+ cells revealed a distinct ITGA6+ITGB4+ mitotic population whose proliferation further segregated to a TNFRSF12Ahi subfraction comprising ~10% of KRT5+ basal cells, residing in clusters within terminal bronchioles and exhibiting enriched clonogenic organoid growth activity. Distal lung organoids were created with apical-out polarity to display ACE2 on the exposed external surface, facilitating SARS-CoV-2 infection of AT2 and basal cultures and identifying club cells as a novel target population. This long-term, feeder-free organoid culture of human distal lung, coupled with single cell analysis, identifies unsuspected basal cell functional heterogeneity and establishes a facile in vitro organoid model for human distal lung infections including COVID-19-associated pneumonia.
View details for DOI 10.1038/s41586-020-3014-1
View details for PubMedID 33238290
SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes
We investigated SARS-CoV-2 potential tropism by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. We co-detected these transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission. These genes are co-expressed in nasal epithelial cells with genes involved in innate immunity, highlighting the cells' potential role in initial viral infection, spread and clearance. The study offers a useful resource for further lines of inquiry with valuable clinical samples from COVID-19 patients and we provide our data in a comprehensive, open and user-friendly fashion at www.covid19cellatlas.org.
View details for DOI 10.1038/s41591-020-0868-6
View details for Web of Science ID 000528517900001
View details for PubMedID 32327758
Niche Cells and Signals that Regulate Lung Alveolar Stem Cells In Vivo.
Cold Spring Harbor perspectives in biology
The distal lung is a honeycomb-like collection of delicate gas exchange sacs called alveoli lined by two interspersed epithelial cell types: the cuboidal, surfactant-producing alveolar type II (AT2) and the flat, gas-exchanging alveolar type I (AT1) cell. During aging, a subset of AT2 cells expressing the canonical Wnt target gene, Axin2, function as stem cells, renewing themselves while generating new AT1 and AT2 cells. Wnt activity endows AT2 cells with proliferative competency, enabling them to respond to activating cues, and simultaneously blocks AT2 to AT1 cell transdifferentiation. Acute alveolar injury rapidly expands the AT2 stem cell pool by transiently inducing Wnt signaling activity in "bulk" AT2 cells, facilitating rapid epithelial repair. AT2 cell "stemness" is thus tightly regulated by access to Wnts, supplied by a specialized single-cell fibroblast niche during maintenance and by AT2 cells themselves during injury repair. Two non-AT2 "reserve" cell populations residing in the distal airways also contribute to alveolar repair, but only after widespread epithelial injury, when they rapidly proliferate, migrate, and differentiate into airway and alveolar lineages. Here, we review alveolar renewal and repair with a focus on the niches, rather than the stem cells, highlighting what is known about the cellular and molecular mechanisms by which they control stem cell activity in vivo.
View details for DOI 10.1101/cshperspect.a035717
View details for PubMedID 32179507
An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics.
2019; 10 (1): 963
Aging promotes lung function decline and susceptibility to chronic lung diseases, which are the third leading cause of death worldwide. Here, we use single cell transcriptomics and mass spectrometry-based proteomics to quantify changes in cellular activity statesacross30 cell types and chart the lung proteome of young and old mice. We show that aging leads to increased transcriptional noise, indicating deregulated epigenetic control. We observe cell type-specific effects of aging, uncovering increased cholesterol biosynthesis in type-2 pneumocytes and lipofibroblasts and altered relative frequency of airway epithelial cells as hallmarks of lung aging. Proteomic profiling reveals extracellular matrix remodeling in old mice, including increased collagen IV and XVI and decreased Fraser syndrome complex proteins and collagen XIV. Computational integration of the aging proteome with the single cell transcriptomes predicts the cellular source of regulated proteins and creates an unbiased reference map of the aging lung.
View details for PubMedID 30814501
High-Efficiency, Selection-free Gene Repair in Airway Stem Cells from Cystic Fibrosis Patients Rescues CFTR Function in Differentiated Epithelia.
Cell stem cell
Cystic fibrosis (CF) is a monogenic disorder caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. Mortality in CF patients is mostly due to respiratory sequelae. Challenges with gene delivery have limited attempts to treat CF using in vivo gene therapy, and low correction levels have hindered ex vivo gene therapy efforts. We have used Cas9 and adeno-associated virus 6 to correct the ΔF508 mutation in readily accessible upper-airway basal stem cells (UABCs) obtained from CF patients. On average, we achieved 30%-50% allelic correction in UABCs and bronchial epithelial cells (HBECs) from 10 CF patients and observed 20%-50% CFTR function relative to non-CF controls in differentiated epithelia. Furthermore, we successfully embedded the corrected UABCs on an FDA-approved porcine small intestinal submucosal membrane (pSIS), and they retained differentiation capacity. This study supports further development of genetically corrected autologous airway stem cell transplant as a treatment for CF.
View details for DOI 10.1016/j.stem.2019.11.002
View details for PubMedID 31839569
Single-cell Wnt signaling niches maintain stemness of alveolar type 2 cells.
Science (New York, N.Y.)
Alveoli, the lung's respiratory units, are tiny sacs where oxygen enters the bloodstream. They are lined by flat AT1 cells, which mediate gas exchange, and AT2 cells, which secret surfactant. Rare AT2s also function as alveolar stem cells. We show that AT2 lung stem cells display active Wnt signaling and many of them are near single, Wnt-expressing fibroblasts. Blocking Wnt secretion depletes these stem cells. Daughter cells leaving the Wnt niche transdifferentiate into AT1s: maintaining Wnt signaling prevents transdifferentiation whereas abrogating Wnt signaling promotes it. Injury induces AT2 autocrine Wnts, recruiting 'bulk' AT2s as progenitors. Thus, individual AT2 stem cells reside in single cell fibroblast niches providing juxtacrine Wnts that maintain them, whereas injury induces autocrine Wnts that transiently expand the progenitor pool. This simple niche maintains the gas exchange surface, and is coopted in cancer.
View details for PubMedID 29420258
Automated cell type classification in intact tissues by single-cell molecular profiling.
A major challenge in biology is identifying distinct cell classes and mapping their interactions in vivo. Tissue-dissociative technologies enable deep single cell molecular profiling but do not provide spatial information. We developed a proximity ligation- in situ hybridization technology (PLISH) with exceptional signal strength, specificity, and sensitivity in tissue. Multiplexed data sets can be acquired using barcoded probes and rapid label-image-erase cycles, with automated calculation of single cell profiles, enabling clustering and anatomical re-mapping of cells. We apply PLISH to expression profile ~2,900 cells in intact mouse lung, which identifies and localizes known cell types, including rare ones. Unsupervised classification of the cells indicates differential expression of 'housekeeping' genes between cell types, and re-mapping of two sub-classes of Club cells highlights their segregated spatial domains in terminal airways. By enabling single cell profiling of various RNA species in situ, PLISH can impact many areas of basic and medical research.
View details for PubMedID 29319504
Trinucleotide repeat containing 6c (TNRC6c) is essential for microvascular maturation during distal airspace sacculation in the developing lung.
2017; 430 (1): 214-223
GW182 (also known asTNRC6) family members are critically involved in the final effector phase of miRNA-mediated mRNA repression. The three mammalian paralogs, TNRC6a, b and c, are thought to be redundant based on Argonaute (Ago) binding, tethering assays, and RNAi silencing of individual members in cell lines. To test this idea, we generated TNRC6a, b and c knockout mice. TNRC6a mutants die at mid-gestation, while b- and c- deleted mice are born at a Mendelian ratio. However, the majority of TNRC6b and all TNRC6c mutants die within 24h after birth, the latter with respiratory failure. Necropsy of TNRC6c mutants revealed normal-appearing airways that give rise to abnormally thick-walled distal gas exchange sacs. Immunohistological analysis of mutant lungs demonstrated a normal distribution of bronchiolar and alveolar cells, indicating that loss of TNRC6c did not abrogate epithelial cell differentiation. The cellular kinetics and relative proportions of endothelial, epithelial, and mesenchymal cells were also not altered. However, the underlying capillary network was simplified and endothelial cells had failed to become tightly apposed to the surface epithelium in TNRC6c mutants, presumably causing the observed respiratory failure. TGFβ family mutant mice exhibit a similar lung phenotype of thick-walled air sacs and neonatal lethality, and qRT-PCR confirmed dynamic downregulation of TGFβ1 and TGFβR2 in TNRC6c mutant lungs during sacculation. VEGFR, but not VEGF-A ligand, was also lower, likely reflecting the overall reduced capillary density in TNRC6c mutants. Together, these results demonstrate that GW182 paralogs are not functionally redundant in vivo. Surprisingly, despite regulating a general cellular process, TNRC6c is selectively required only in the distal lung and not until late in gestation for proper expression of the TGFβ family genes that drive sacculation. These results imply a complex and indirect mode of regulation of sacculation by TNRC6c, mediated in part by dynamic transcriptional repression of an inhibitor of TGFβ family gene expression.
View details for DOI 10.1016/j.ydbio.2017.07.018
View details for PubMedID 28811219
Keeping it together: Pulmonary alveoli are maintained by a hierarchy of cellular programs.
2015; 37 (9): 1028-1037
The application of in vivo genetic lineage tracing has advanced our understanding of cellular mechanisms for tissue renewal in organs with slow turnover, like the lung. These studies have identified an adult stem cell with very different properties than classically understood ones that maintain continuously cycling tissues such as the intestine. A portrait has emerged of an ensemble of cellular programs that replenish the cells that line the gas exchange (alveolar) surface, enabling a response tailored to the extent of cell loss. A capacity for differentiated cells to undergo direct lineage transitions allows for local restoration of proper cell balance at sites of injury. We present these recent findings as a paradigm for how a relatively quiescent tissue compartment can maintain homeostasis throughout a lifetime punctuated by injuries ranging from mild to life-threatening, and discuss how dysfunction or insufficiency of alveolar repair programs produce serious health consequences like cancer and fibrosis.
View details for DOI 10.1002/bies.201500031
View details for PubMedID 26201286
Cellular mechanisms of alveolar pathology in childhood interstitial lung diseases: current insights from mouse genetics
CURRENT OPINION IN PEDIATRICS
2015; 27 (3): 341-347
Childhood interstitial lung diseases (ILDs) are a diverse class of disorders affecting the alveolar gas exchange region that lack specific treatments and are usually fatal. Here, we integrate recent insights into alveolar cell biology with histopathology from well characterized mutations of surfactant-associated genes. We take a reductionist approach by parsing discrete histological features and correlating each to perturbation of a particular function of the alveolar epithelial type II (AT2) cell, the central driver of disease, to generate a working model for the cellular mechanisms of disease pathogenesis.The application of genetically modified mice and single cell genomics has yielded new insights into lung biology, including the identification of a bipotent alveolar progenitor in development, mapping of adult AT2 stem cells in vivo, and demonstration that latent cooperative interactions with fibroblasts can be pathologically activated by targeted injury of the AT2 cell.As we learn more about individual and cooperative roles for alveolar cells in health, we can dissect how perturbations of specific cellular functions contribute to disease in childhood ILDs. We hope our updated model centered around the AT2 cell as the initiator of disease provides a cellular framework that researchers can build upon and revise as they identify the specific molecular signals within and between alveolar cells that mediate the diverse pathologic features, so that targeted pharmacologic and cell-based treatments for patients can ultimately be engineered.
View details for DOI 10.1097/MOP.0000000000000227
View details for Web of Science ID 000354214800013
View details for PubMedID 25888154
View details for PubMedCentralID PMC4466102
Reconstructing lineage hierarchies of the distal lung epithelium using single-cell RNA-seq.
2014; 509 (7500): 371-375
The mammalian lung is a highly branched network in which the distal regions of the bronchial tree transform during development into a densely packed honeycomb of alveolar air sacs that mediate gas exchange. Although this transformation has been studied by marker expression analysis and fate-mapping, the mechanisms that control the progression of lung progenitors along distinct lineages into mature alveolar cell types are still incompletely known, in part because of the limited number of lineage markers and the effects of ensemble averaging in conventional transcriptome analysis experiments on cell populations. Here we show that single-cell transcriptome analysis circumvents these problems and enables direct measurement of the various cell types and hierarchies in the developing lung. We used microfluidic single-cell RNA sequencing (RNA-seq) on 198 individual cells at four different stages encompassing alveolar differentiation to measure the transcriptional states which define the developmental and cellular hierarchy of the distal mouse lung epithelium. We empirically classified cells into distinct groups by using an unbiased genome-wide approach that did not require a priori knowledge of the underlying cell types or the previous purification of cell populations. The results confirmed the basic outlines of the classical model of epithelial cell-type diversity in the distal lung and led to the discovery of many previously unknown cell-type markers, including transcriptional regulators that discriminate between the different populations. We reconstructed the molecular steps during maturation of bipotential progenitors along both alveolar lineages and elucidated the full life cycle of the alveolar type 2 cell lineage. This single-cell genomics approach is applicable to any developing or mature tissue to robustly delineate molecularly distinct cell types, define progenitors and lineage hierarchies, and identify lineage-specific regulatory factors.
View details for DOI 10.1038/nature13173
View details for PubMedID 24739965
Alveolar progenitor and stem cells in lung development, renewal and cancer.
2014; 507 (7491): 190-194
View details for DOI 10.1038/nature12930
View details for PubMedID 24499815
Stem cells: Differentiated cells in a back-up role.
2013; 503 (7475): 204-205
View details for DOI 10.1038/nature12706
View details for PubMedID 24196710
Distinct roles for retinoic acid receptors alpha and beta in early lung morphogenesis
2006; 291 (1): 12-24
Retinoic acid (RA) signaling is required for normal development of multiple organs. However, little is known about how RA influences the initial stages of lung development. Here, we used a combination of genetic, pharmacological and explant culture approaches to address this issue, and to investigate how signaling by different RA receptors (RAR) mediates the RA effects. We analyzed initiation of lung development in retinaldehyde dehydrogenase-2 (Raldh2) null mice, a model in which RA signaling is absent from the foregut from its earliest developmental stages. We provide evidence that RA is dispensable for specification of lung cell fate in the endoderm. By using synthetic retinoids to selectively activate RAR alpha or beta signaling in this model, we demonstrate novel and unique functions of these receptors in the early lung. We show that activation of RAR beta, but not alpha, induces expression of the fibroblast growth factor Fgf10 and bud morphogenesis in the lung field. Similar analysis of wild type foregut shows that endogenous RAR alpha activity is required to maintain overall RA signaling, and to refine the RAR beta effects in the lung field. Our data support the idea that balanced activation of RAR alpha and beta is critical for proper lung bud initiation and endodermal differentiation.
View details for DOI 10.1016/j.ydbio.2005.10.045
View details for Web of Science ID 000236128300002
View details for PubMedID 16427040
Retinoic acid selectively regulates Fgf10 expression and maintains cell identity in the prospective lung field of the developing foregut
2004; 273 (2): 402-415
Although respiratory tract defects that result from disruption of retinoic acid (RA) signaling have been widely reported, the mechanism by which endogenous RA regulates early lung morphogenesis is unknown. Here, we provide novel evidence that a major role for RA is to selectively maintain mesodermal proliferation and induce fibroblast growth factor 10 (Fgf10) expression in the foregut region where the lung forms. By using a pan-RAR antagonist (BMS493) in foregut explant cultures, we show that bud initiation is selectively blocked in the prospective respiratory region by failure to induce Fgf10 in the corresponding mesoderm. The RA regulation of Fgf10 expression occurs only in this region, within a defined developmental window, and is not seen in other foregut derivatives such as thyroid and pancreas where Fgf10 is also required for normal development. Furthermore, we show that RA activity is essential in the lung field to maintain lung cell identity in the endoderm; RAR antagonism disrupts expression of thyroid transcription factor 1 (Ttf1), an early marker of the respiratory region in the endoderm, and surfactant protein C (Sp-C) mRNAs. Our observations in mouse foregut cultures are corroborated by data from an in vivo model of vitamin A deficiency in rats. Our study supports RA as an essential regulator of gene expression and cellular activities during primary bud formation.
View details for DOI 10.1016/j.ydbio.2004.04.039
View details for Web of Science ID 000223681000018
View details for PubMedID 15328022
- COPD: Clinical Manifestations, Diagnosis, and Treatment Baum's Textbook of Pulmonary Diseases (Eds: James D. Crapo, Jeffrey Glassroth, Joel Karlinsky, and Talmadge E. King Jr.) 2004; 7th ed
Growth factors in lung development and disease: friends or foe?
2002; 3: 2-?
Growth factors mediate tissue interactions and regulate a variety of cellular functions that are critical for normal lung development and homeostasis. Besides their involvement in lung pattern formation, growth and cell differentiation during organogenesis, these factors have been also implicated in modulating injury-repair responses of the adult lung. Altered expression of growth factors, such as transforming growth factor beta1, vascular endothelial growth factor and epidermal growth factor, and/or their receptors, has been found in a number of pathological lung conditions. In this paper, we discuss the dual role of these molecules in mediating beneficial feedback responses or responses that can further damage lung integrity; we shall also discuss the basis for their prospective use as therapeutic agents.
View details for PubMedID 11806837
View details for PubMedCentralID PMC64813