TY  - JOUR
A1  - Liu, Fengming
A1  - Han, Kun
A1  - Blair, Robert
A1  - Kenst, Kornelia
A1  - Qin, Zhongnan
A1  - Upcin, Berin
A1  - Wörsdörfer, Philipp
A1  - Midkiff, Cecily C.
A1  - Mudd, Joseph
A1  - Belyaeva, Elizaveta
A1  - Milligan, Nicholas S.
A1  - Rorison, Tyler D.
A1  - Wagner, Nicole
A1  - Bodem, Jochen
A1  - Dölken, Lars
A1  - Aktas, Bertal H.
A1  - Vander Heide, Richard S.
A1  - Yin, Xiao-Ming
A1  - Kolls, Jay K.
A1  - Roy, Chad J.
A1  - Rappaport, Jay
A1  - Ergün, Süleyman
A1  - Qin, Xuebin
T1  - SARS-CoV-2 Infects Endothelial Cells In Vivo and In Vitro
JF  - Frontiers in Cellular and Infection Microbiology
N2  - SARS-CoV-2 infection can cause fatal inflammatory lung pathology, including thrombosis and increased pulmonary vascular permeability leading to edema and hemorrhage. In addition to the lung, cytokine storm-induced inflammatory cascade also affects other organs. SARS-CoV-2 infection-related vascular inflammation is characterized by endotheliopathy in the lung and other organs. Whether SARS-CoV-2 causes endotheliopathy by directly infecting endothelial cells is not known and is the focus of the present study. We observed 1) the co-localization of SARS-CoV-2 with the endothelial cell marker CD31 in the lungs of SARS-CoV-2-infected mice expressing hACE2 in the lung by intranasal delivery of adenovirus 5-hACE2 (Ad5-hACE2 mice) and non-human primates at both the protein and RNA levels, and 2) SARS-CoV-2 proteins in endothelial cells by immunogold labeling and electron microscopic analysis. We also detected the co-localization of SARS-CoV-2 with CD31 in autopsied lung tissue obtained from patients who died from severe COVID-19. Comparative analysis of RNA sequencing data of the lungs of infected Ad5-hACE2 and Ad5-empty (control) mice revealed upregulated KRAS signaling pathway, a well-known pathway for cellular activation and dysfunction. Further, we showed that SARS-CoV-2 directly infects mature mouse aortic endothelial cells (AoECs) that were activated by performing an aortic sprouting assay prior to exposure to SARS-CoV-2. This was demonstrated by co-localization of SARS-CoV-2 and CD34 by immunostaining and detection of viral particles in electron microscopic studies. Moreover, the activated AoECs became positive for ACE-2 but not quiescent AoECs. Together, our results indicate that in addition to pneumocytes, SARS-CoV-2 also directly infects mature vascular endothelial cells in vivo and ex vivo, which may contribute to cardiovascular complications in SARS-CoV-2 infection, including multipleorgan failure.
KW  - endothelial cell infection
KW  - animal models
KW  - SARS-CoV-2
KW  - aorta ring
KW  - hACE2
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241948
SN  - 2235-2988
VL  - 11
ER  - 
TY  - JOUR
A1  - Aktas, Bertal H.
A1  - Upcin, Berin
A1  - Henke, Erik
A1  - Padmasekar, Manju
A1  - Qin, Xuebin
A1  - Ergün, Süleyman
T1  - The Best for the Most Important: Maintaining a Pristine Proteome in Stem and Progenitor Cells
JF  - Stem Cells International
N2  - Pluripotent stem cells give rise to reproductively enabled offsprings by generating progressively lineage-restricted multipotent stem cells that would differentiate into lineage-committed stem and progenitor cells. These lineage-committed stem and progenitor cells give rise to all adult tissues and organs. Adult stem and progenitor cells are generated as part of the developmental program and play critical roles in tissue and organ maintenance and/or regeneration. The ability of pluripotent stem cells to self-renew, maintain pluripotency, and differentiate into a multicellular organism is highly dependent on sensing and integrating extracellular and extraorganismal cues. Proteins perform and integrate almost all cellular functions including signal transduction, regulation of gene expression, metabolism, and cell division and death. Therefore, maintenance of an appropriate mix of correctly folded proteins, a pristine proteome, is essential for proper stem cell function. The stem cells' proteome must be pristine because unfolded, misfolded, or otherwise damaged proteins would interfere with unlimited self-renewal, maintenance of pluripotency, differentiation into downstream lineages, and consequently with the development of properly functioning tissue and organs. Understanding how various stem cells generate and maintain a pristine proteome is therefore essential for exploiting their potential in regenerative medicine and possibly for the discovery of novel approaches for maintaining, propagating, and differentiating pluripotent, multipotent, and adult stem cells as well as induced pluripotent stem cells. In this review, we will summarize cellular networks used by various stem cells for generation and maintenance of a pristine proteome. We will also explore the coordination of these networks with one another and their integration with the gene regulatory and signaling networks.
KW  - Endoplasmic-Reticulum Stress
KW  - Heme-regulated inhibitor
KW  - Human Muse Cells
KW  - Transcription factor NRF1
KW  - ER-Stress
KW  - Hematopoietic Stem
KW  - Quality-control
KW  - Messenger-RNAs
KW  - Neural Differentiation
KW  - Translation Initiation
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227769
ER  -