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Article ; Online: Coming to "Grp(s)" with Senescence in the Alveolar Epithelium.

Winters, Nichelle I / Kropski, Jonathan A

American journal of respiratory and critical care medicine

2019 Volume 201, Issue 2, Page(s) 134–136

MeSH term(s)	Cellular Senescence ; Endoplasmic Reticulum Stress ; Humans ; Pulmonary Fibrosis ; Respiratory Mucosa
Language	English
Publishing date	2019-12-03
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.201910-2052ED
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Article ; Online: Epithelial Injury and Dysfunction in the Pathogenesis of Idiopathic PulmonaryFibrosis.

Winters, Nichelle I / Burman, Ankita / Kropski, Jonathan A / Blackwell, Timothy S

The American journal of the medical sciences

2019 Volume 357, Issue 5, Page(s) 374–378

Abstract: Idiopathic pulmonary fibrosis is a disease of older adults leading to progressive dyspnea and reduced exercise capacity, typically resulting in death within 3-5years of diagnosis. Underlying genetic susceptibility combined with environmental insults is ... ...

Abstract	Idiopathic pulmonary fibrosis is a disease of older adults leading to progressive dyspnea and reduced exercise capacity, typically resulting in death within 3-5years of diagnosis. Underlying genetic susceptibility combined with environmental insults is proposed to trigger a chronic wound repair response, leading to activation of the fibrotic cascade. Perturbations in several molecular pathways mediate vulnerability of the alveolar epithelium to injurious agents, including the unfolded protein response, autophagy, mitophagy, and cellular senescence. These cellular responses are intricately intertwined and link genetic susceptibility to the progressive fibrotic phenotype. Ongoing studies investigating these pathways in type II alveolar epithelial cells show promise for identifying new targeted interventions that could prevent or halt the progression of IPF.
MeSH term(s)	Aged ; Alveolar Epithelial Cells/physiology ; Humans ; Idiopathic Pulmonary Fibrosis/physiopathology ; Idiopathic Pulmonary Fibrosis/therapy ; Middle Aged
Language	English
Publishing date	2019-01-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	82078-7
ISSN	1538-2990 ; 0002-9629
ISSN (online)	1538-2990
ISSN	0002-9629
DOI	10.1016/j.amjms.2019.01.010
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Article ; Online: Resident progenitors, not exogenous migratory cells, generate the majority of visceral mesothelium in organogenesis.

Winters, Nichelle I / Williams, Annabelle M / Bader, David M

Developmental biology

2014 Volume 391, Issue 2, Page(s) 125–132

Abstract: Historically, analyses of mesothelial differentiation have focused on the heart where a highly migratory population of progenitors originating from a localized "extrinsic" source moves to and over the developing organ. This model long stood alone as the ... ...

Abstract	Historically, analyses of mesothelial differentiation have focused on the heart where a highly migratory population of progenitors originating from a localized "extrinsic" source moves to and over the developing organ. This model long stood alone as the paradigm for generation of this cell type. Here, using chick/quail chimeric grafting and subsequent identification of mesothelial cell populations, we demonstrate that a different mechanism for the generation of mesothelia exists in vertebrate organogenesis. In this newly discovered model, mesothelial progenitors are intrinsic to organs of the developing digestive and respiratory systems. Additionally, we demonstrate that the early heart stands alone in its ability to recruit an entirely exogenous mesothelial cell layer during development. Thus, the newly identified "organ intrinsic" model of mesotheliogenesis appears to predominate while the long-studied cardiac model of mesothelial development may be the outlier.
MeSH term(s)	Animals ; Cell Differentiation ; Cell Movement ; Chick Embryo ; Chimera ; Embryonic Stem Cells/metabolism ; Epithelium/embryology ; Gastrointestinal Tract/embryology ; Heart/embryology ; Organogenesis ; Quail ; Respiratory System/embryology
Language	English
Publishing date	2014-04-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1114-9
ISSN	1095-564X ; 0012-1606
ISSN (online)	1095-564X
ISSN	0012-1606
DOI	10.1016/j.ydbio.2014.04.003
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Article ; Online: Tenosynovial chondromatosis of the flexor hallucis longus in a 17-year-old girl.

Winters, Nichelle I / Thomson, A Brian / Flores, Raina R / Jordanov, Martin I

Pediatric radiology

2015 Volume 45, Issue 12, Page(s) 1874–1877

Abstract: Tenosynovial chondromatosis is a benign chondrogenic metaplasia of extra-articular synovial tissue. The most common locations for tenosynovial chondromatosis to develop are the hands and feet. The condition has rarely been reported in children. We ... ...

Abstract	Tenosynovial chondromatosis is a benign chondrogenic metaplasia of extra-articular synovial tissue. The most common locations for tenosynovial chondromatosis to develop are the hands and feet. The condition has rarely been reported in children. We present a case of tenosynovial chondromatosis of the flexor hallucis longus in a 17-year-old girl. The presentation was unusual not only due to the location and young age of the patient but also the absence of any palpable mass on physical exam and complete lack of calcification of the cartilage bodies. Initial diagnosis was made by MRI. The patient underwent tenosynovectomy with an excellent postoperative recovery at 6-month follow-up. Histopathology confirmed the diagnosis of tenosynovial chondromatosis.
MeSH term(s)	Adolescent ; Ankle/pathology ; Ankle/surgery ; Chondromatosis, Synovial/pathology ; Chondromatosis, Synovial/surgery ; Contrast Media ; Female ; Gadolinium ; Humans ; Image Enhancement ; Magnetic Resonance Imaging ; Tendons/pathology ; Tendons/surgery
Chemical Substances	Contrast Media ; Gadolinium (AU0V1LM3JT)
Language	English
Publishing date	2015-11
Publishing country	Germany
Document type	Case Reports ; Journal Article
ZDB-ID	124459-0
ISSN	1432-1998 ; 0301-0449
ISSN (online)	1432-1998
ISSN	0301-0449
DOI	10.1007/s00247-015-3383-z
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Article ; Online: Comprehensive timeline of mesodermal development in the quail small intestine.

Thomason, Rebecca T / Bader, David M / Winters, Nichelle I

Developmental dynamics : an official publication of the American Association of Anatomists

2012 Volume 241, Issue 11, Page(s) 1678–1694

Abstract: Background: To generate the mature intestine, splanchnic mesoderm diversifies into six different tissue layers each with multiple cell types through concurrent and complex morphogenetic events. Hindering the progress of research in the field is the lack ...

Abstract	Background: To generate the mature intestine, splanchnic mesoderm diversifies into six different tissue layers each with multiple cell types through concurrent and complex morphogenetic events. Hindering the progress of research in the field is the lack of a detailed description of the fundamental morphological changes that constitute development of the intestinal mesoderm. Results: We used immunofluorescence and morphometric analyses of wild-type and Tg(tie1:H2B-eYFP) quail embryos to establish a comprehensive timeline of mesodermal development in the avian intestine. The following landmark features were analyzed from appearance of the intestinal primordium through generation of the definitive structure: radial compartment formation, basement membrane dynamics, mesothelial differentiation, mesenchymal expansion and growth patterns, smooth muscle differentiation, and maturation of the vasculature. In this way, structural relationships between mesodermal components were identified over time. Conclusions: This integrated analysis presents a roadmap for investigators and clinicians to evaluate diverse experimental data obtained at individual stages of intestinal development within the longitudinal context of intestinal morphogenesis.
MeSH term(s)	Animals ; Fluorescent Antibody Technique ; Gene Expression Regulation, Developmental ; Intestine, Small/embryology ; Intestine, Small/metabolism ; Mesoderm/growth & development ; Mesoderm/metabolism ; Microscopy, Fluorescence ; Quail
Language	English
Publishing date	2012-09-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1102541-4
ISSN	1097-0177 ; 1058-8388
ISSN (online)	1097-0177
ISSN	1058-8388
DOI	10.1002/dvdy.23855
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Article ; Online: Identification of a novel developmental mechanism in the generation of mesothelia.

Winters, Nichelle I / Thomason, Rebecca T / Bader, David M

Development (Cambridge, England)

2012 Volume 139, Issue 16, Page(s) 2926–2934

Abstract: Mesothelium is the surface layer of all coelomic organs and is crucial for the generation of their vasculature. Still, our understanding of the genesis of this essential cell type is restricted to the heart where a localized exogenous population of cells, ...

Abstract	Mesothelium is the surface layer of all coelomic organs and is crucial for the generation of their vasculature. Still, our understanding of the genesis of this essential cell type is restricted to the heart where a localized exogenous population of cells, the proepicardium, migrates to and envelops the myocardium supplying mesothelial, vascular and stromal cell lineages. Currently it is not known whether this pattern of development is specific to the heart or applies broadly to other coelomic organs. Using two independent long-term lineage-tracing studies, we demonstrate that mesothelial progenitors of the intestine are intrinsic to the gut tube anlage. Furthermore, a novel chick-quail chimera model of gut morphogenesis reveals these mesothelial progenitors are broadly distributed throughout the gut primordium and are not derived from a localized and exogenous proepicardium-like source of cells. These data demonstrate an intrinsic origin of mesothelial cells to a coelomic organ and provide a novel mechanism for the generation of mesothelial cells.
MeSH term(s)	Animals ; Animals, Genetically Modified ; Cell Lineage ; Chick Embryo ; Coturnix ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/metabolism ; Epithelial Cells/cytology ; Epithelial Cells/metabolism ; Epithelium/embryology ; Epithelium/metabolism ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; Intestinal Mucosa/metabolism ; Intestines/cytology ; Intestines/embryology ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Transplantation Chimera/embryology ; Transplantation Chimera/genetics ; Transplantation Chimera/metabolism
Chemical Substances	Recombinant Proteins ; Green Fluorescent Proteins (147336-22-9)
Language	English
Publishing date	2012-07-04
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	90607-4
ISSN	1477-9129 ; 0950-1991
ISSN (online)	1477-9129
ISSN	0950-1991
DOI	10.1242/dev.082396
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Article: Resident progenitors, not exogenous migratory cells, generate the majority of visceral mesothelium in organogenesis

Winters, Nichelle I / Williams, Annabelle M / Bader, David M

Developmental biology. 2014 July 15, v. 391, no. 2

2014

Abstract: Historically, analyses of mesothelial differentiation have focused on the heart where a highly migratory population of progenitors originating from a localized “extrinsic” source moves to and over the developing organ. This model long stood alone as the ... ...

Abstract	Historically, analyses of mesothelial differentiation have focused on the heart where a highly migratory population of progenitors originating from a localized “extrinsic” source moves to and over the developing organ. This model long stood alone as the paradigm for generation of this cell type. Here, using chick/quail chimeric grafting and subsequent identification of mesothelial cell populations, we demonstrate that a different mechanism for the generation of mesothelia exists in vertebrate organogenesis. In this newly discovered model, mesothelial progenitors are intrinsic to organs of the developing digestive and respiratory systems. Additionally, we demonstrate that the early heart stands alone in its ability to recruit an entirely exogenous mesothelial cell layer during development. Thus, the newly identified “organ intrinsic” model of mesotheliogenesis appears to predominate while the long-studied cardiac model of mesothelial development may be the outlier.
Keywords	cell movement ; chicks ; heart ; models ; organogenesis ; quails
Language	English
Dates of publication	2014-0715
Size	p. 125-132.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	1114-9
ISSN	1095-564X ; 0012-1606
ISSN (online)	1095-564X
ISSN	0012-1606
DOI	10.1016/j.ydbio.2014.04.003
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Article ; Online: Thromboxane-Prostanoid Receptor Signaling Drives Persistent Fibroblast Activation in Pulmonary Fibrosis.

American journal of respiratory and critical care medicine

2022 Volume 206, Issue 5, Page(s) 596–607

Abstract: Rationale: ...

Abstract	Rationale:
MeSH term(s)	Animals ; Bleomycin/pharmacology ; F2-Isoprostanes/metabolism ; Fibroblasts/metabolism ; Humans ; Idiopathic Pulmonary Fibrosis/genetics ; Lung/metabolism ; Mice ; Mice, Inbred C57BL ; Prostaglandins/metabolism ; Receptors, Thromboxane/metabolism ; Thromboxanes/metabolism ; Transforming Growth Factor beta/metabolism
Chemical Substances	F2-Isoprostanes ; Prostaglandins ; Receptors, Thromboxane ; Thromboxanes ; Transforming Growth Factor beta ; Bleomycin (11056-06-7)
Language	English
Publishing date	2022-06-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202106-1503OC
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Article ; Online: Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity.

Nature communications

2021 Volume 12, Issue 1, Page(s) 4314

Abstract: Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyze the transcriptomes of 611,398 single cells isolated from healthy and CLD lungs to identify molecular ... ...

Abstract	Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyze the transcriptomes of 611,398 single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in patients with chronic lung diseases. We observe a similar cellular distribution and relative expression of SARS-CoV-2 entry factors in control and CLD lungs. CLD AT2 cells express higher levels of genes linked directly to the efficiency of viral replication and the innate immune response. Additionally, we identify basal differences in inflammatory gene expression programs that highlight how CLD alters the inflammatory microenvironment encountered upon viral exposure to the peripheral lung. Our study indicates that CLD is accompanied by changes in cell-type-specific gene expression programs that prime the lung epithelium for and influence the innate and adaptive immune responses to SARS-CoV-2 infection.
MeSH term(s)	Alveolar Epithelial Cells/metabolism ; Alveolar Epithelial Cells/pathology ; Angiotensin-Converting Enzyme 2/genetics ; Angiotensin-Converting Enzyme 2/metabolism ; COVID-19/genetics ; COVID-19/pathology ; Chronic Disease ; Humans ; Idiopathic Pulmonary Fibrosis/genetics ; Idiopathic Pulmonary Fibrosis/pathology ; Immunity, Innate/genetics ; Inflammation/genetics ; Lung/metabolism ; Lung/pathology ; Lung Diseases/genetics ; Lung Diseases/pathology ; SARS-CoV-2/pathogenicity ; SARS-CoV-2/physiology ; Transcriptome ; Virus Internalization ; Virus Replication/genetics
Chemical Substances	ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2021-07-14
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-24467-0
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Article: Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity.

bioRxiv : the preprint server for biology

2021

Abstract: Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyzed the transcriptomes of 605,904 single cells isolated from healthy and CLD lungs to identify molecular ... ...

Abstract	Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyzed the transcriptomes of 605,904 single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in patients with chronic lung diseases. We observed a similar cellular distribution and relative expression of SARS-CoV-2 entry factors in control and CLD lungs. CLD epithelial cells expressed higher levels of genes linked directly to the efficiency of viral replication and innate immune response. Additionally, we identified basal differences in inflammatory gene expression programs that highlight how CLD alters the inflammatory microenvironment encountered upon viral exposure to the peripheral lung. Our study indicates that CLD is accompanied by changes in cell-type-specific gene expression programs that prime the lung epithelium for and influence the innate and adaptive immune responses to SARS-CoV-2 infection.
Keywords	covid19
Language	English
Publishing date	2021-01-04
Publishing country	United States
Document type	Preprint
DOI	10.1101/2020.10.20.347187
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