scholarly journals Intravital microscopy to illuminate cell state plasticity during metastasis

2021 ◽  
Vol 72 ◽  
pp. 28-35
Author(s):  
Jacco van Rheenen ◽  
Colinda L.G.J. Scheele
Author(s):  
Aparna Nathan ◽  
Jessica Beynor ◽  
Yuriy Baglaenko ◽  
Sara Suliman ◽  
Kazuyoshi Ishigaki ◽  
...  
Keyword(s):  
T Cells ◽  

Author(s):  
Emmanuel Gabriel ◽  
Minhyung Kim ◽  
Daniel Fisher ◽  
Catherine Mangum ◽  
Kristopher Attwood ◽  
...  

Author(s):  
Kevin Y. Huang ◽  
Enrico Petretto

Single-cell transcriptomics analyses of the fibrotic lung uncovered two cell states critical to lung injury recovery in the alveolar epithelium- a reparative transitional cell state in the mouse and a disease-specific cell state (KRT5-/KRT17+) in human idiopathic pulmonary fibrosis (IPF). The murine transitional cell state lies between the differentiation from type 2 (AT2) to type 1 pneumocyte (AT1), and the human KRT5-/KRT17+ cell state may arise from the dysregulation of this differentiation process. We review major findings of single-cell transcriptomics analyses of the fibrotic lung and re-analyzed data from 7 single-cell RNA sequencing studies of human and murine models of IPF, focusing on the alveolar epithelium. Our comparative and cross-species single-cell transcriptomics analyses allowed us to further delineate the differentiation trajectories from AT2 to AT1 and AT2 to the KRT5-/KRT17+ cell state. We observed AT1 cells in human IPF retain the transcriptional signature of the murine transitional cell state. Using pseudotime analysis, we recapitulated the differentiation trajectories from AT2 to AT1 and from AT2 to KRT5-/KRT17+ cell state in multiple human IPF studies. We further delineated transcriptional programs underlying cell state transitions and determined the molecular phenotypes at terminal differentiation. We hypothesize that in addition to the reactivation of developmental programs (SOX4, SOX9), senescence (TP63, SOX4) and the Notch pathway (HES1) are predicted to steer intermediate progenitors to the KRT5-/KRT17+ cell state. Our analyses suggest that activation of SMAD3 later in the differentiation process may explain the fibrotic molecular phenotype typical of KRT5-/KRT17+ cells.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Emmanuel M. Gabriel ◽  
Minhyung Kim ◽  
Daniel T. Fisher ◽  
Catherine Mangum ◽  
Kristopher Attwood ◽  
...  

AbstractAberrancies in the tumor microvasculature limit the systemic delivery of anticancer agents, which impedes tumor response. Using human intravital microscopy (HIVM), we hypothesized that HIVM would be feasible in patients with peritoneal carcinomatosis (PC). During cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for PC, HIVM was performed in both tumor and non-tumor areas. The primary outcome was HIVM feasibility to measure vessel characteristics. We secondarily evaluated associations between HIVM vessel characteristics and oncologic outcomes (RECIST response to neoadjuvant therapy and disease-specific survival). Thirty patients with PC were enrolled. Nineteen patients (63.3%) received neoadjuvant therapy. HIVM was feasible in all patients. Compared to non-tumor (control) areas, PC areas had a lower density of functional vessels, higher proportion of non-functional vessels, smaller lumenal diameters, and lower blood flow velocity. Qualitative differences in these vessel characteristics were observed among patients who had partial response, stable disease, or progressive disease after receiving neoadjuvant therapy. However, no statistically significant relationships were found between HIVM vessel characteristics and oncologic outcomes. These novel findings comprise the first-in-human, real-time evidence of the microscopic differences between normal and tumor-associated vessels and form the basis for our larger, ongoing clinical trial appropriately powered to determine the clinical utility of HIVM (NCT03823144).


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yue Liu ◽  
Zongjin Li

AbstractAcute kidney injury (AKI) is a common clinical symptom, which is mainly manifested by elevated serum creatinine and blood urea nitrogen levels. When AKI is not repaired in time, the patient is prone to develop chronic kidney disease (CKD). The kidney is composed of more than 30 different cells, and its structure is complex. It is extremely challenging to understand the lineage relationships and cell fate of these cells in the process of kidney injury and regeneration. Since the 20th century, lineage tracing technology has provided an important mean for studying organ development, tissue damage repair, and the differentiation and fate of single cells. However, traditional lineage tracing methods rely on sacrificing animals to make tissue slices and then take snapshots with conventional imaging tools to obtain interesting information. This method cannot achieve dynamic and continuous monitoring of cell actions on living animals. As a kind of intravital microscopy (IVM), two-photon microscopy (TPM) has successfully solved the above problems. Because TPM has the ability to penetrate deep tissues and can achieve imaging at the single cell level, lineage tracing technology with TPM is gradually becoming popular. In this review, we provided the key technical elements of lineage tracing, and how to use intravital imaging technology to visualize and quantify the fate of renal cells.


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