scholarly journals Single cell transcriptomics suggest that human adipocyte progenitor cells constitute a homogeneous cell population

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Juan R. Acosta ◽  
Simon Joost ◽  
Kasper Karlsson ◽  
Anna Ehrlund ◽  
Xidan Li ◽  
...  
2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14044-e14044
Author(s):  
Roland Kälin ◽  
Linzhi Cai ◽  
Dongxu Zhao ◽  
Huabin Zhang ◽  
Wenlong Zhang ◽  
...  

e14044 Background: Aggressive brain tumors like glioblastoma depend on support by their local environment. While the role of tumor-associated myeloid cells on glioblastoma progression is well-documented, we have only partial knowledge of the pathological impact of glioblastoma -parenchymal progenitor cells. Methods: We investigated the glioblastoma microenvironment with transgenic lineage-tracing models ( nestin-creER2, R26-tdTomato and sox2-creER2,R26-tdTomato), intravital imaging, single-cell transcriptomics, immunofluorescence and flow-cytometry as well as histopathology and characterized a previously unknown tumor-associated progenitor cell. In functional experiments, we studied the knockout of the transcription factor SOX2 in these tumor-associated cells. Results: Lineage-traced cells from mouse glioblastoma were obtained by flow-cytometry and single cell transcriptomes compared to established gene expression data from brain tumor parenchymal cells. The traced tumor-associated cells had a transcriptomic profile largely resembling myeloid cells and expressed microglia-/macrophage-markers on the protein-level. However, transgenic models and bone-marrow chimera revealed that the traced cells were clearly distinct from microglia or macrophages. The traced tumor associated cells with a myeloid expression profile derived from a SOX2-dependent progenitor cell. Consequently, conditional Sox2-knockout ablated the entire myeloid-like cell population. Remarkably, this tumor-associated cell population had a large impact on disease-progression causing significant reduction of glioblastoma –vascularization to 53%, changing vascular function and leading to a decrease in tumor volume to 42% as compared to controls. The myeloid-like progenitor cells were identified in human brain tumors by immunofluorescence and in scRNA-seq data. Conclusions: We identified a previously unacknowledged population of tumor-associated progenitor cells with a myeloid-like expression profile that transiently appeared during glioblastoma growth. These progenitors have strong impact on glioblastoma progression and point towards a new and promising therapeutic target in order to support anti-angiogenic regimen in glioblastoma.


1968 ◽  
Vol 19 (03/04) ◽  
pp. 483-491 ◽  
Author(s):  
M Nakahara ◽  
D. R Celander

SummaryMitochondrial, lysosomal, and microsomal fractions of pig and cow myocardial cells were screened for their ability to effect lysis of bovine fibrin plates prepared with Profibrinolysin-containing and profibrinolysin-free reagents. Little if any activity was observed on profibrinolysin-free fibrin plates. Maximum activity on Profibrinolysin-containing plates was found in association with the microsomes. Extraction of the microsome preparations with 0.15 M KCl and 2.0 M KCl dissolved activator molecules with different pH solubility and stability characteristics. The activator activity of the 2.0 M KCl extract was in general more stable to acid pH than that of the 0.15 M KCl extract.The activator characteristic of the microsomal suspensions and of both types of microsome extracts was stable to acetone precipitation. However, the 2.0 M KCl extract lost its relatively greater stability to acid pH when precipitated with acetone. The significance of the chemical environment as a determining factor in final properties of purified enzyme molecules is discussed. The importance of using a relatively homogeneous cell population as starting material is also emphasized.


1980 ◽  
Vol 238 (5) ◽  
pp. H740-H744
Author(s):  
W. M. Long ◽  
G. J. Bagby ◽  
J. J. Spitzer

An approach is described that allows metabolic data obtained from a mixture of vital dye-excluding (T-) and nonexcluding (T+) myocytes to be extrapolated to a homogeneous cell population. Myocytes from adult dog hearts were dispersed by enzymatic treatment and separated into two fractions: one containing predominantly T-, and the other containing predominately T+ cells. Measuring the oxidation rate and viability of each fraction allows the determination of the rate of oxidation of a homogeneous cell population when palmitate, glucose, or lactate is the oxidizable substrate. The calculated rate of oxidation of these substrates by 100% T- cells was: 0.15, 0.46, and 2.99 nmol . mg protein-1 . min-1, respectively. Oxidation of palmitate and lactate by T+ cells was one-fifth of the T-cell rate. Glucose oxidation of T+ cells was not significantly different from zero. Use of this procedure will permit study of myocardial metabolism when experimental procedures may cause altered cell viability.


Biology Open ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. bio051797 ◽  
Author(s):  
Aitana M. Castro Colabianchi ◽  
María B. Tavella ◽  
Laura E. Boyadjián López ◽  
Marcelo Rubinstein ◽  
Lucía F. Franchini ◽  
...  

ABSTRACTThe blastula Chordin- and Noggin-expressing (BCNE) center comprises animal-dorsal and marginal-dorsal cells of the amphibian blastula and contains the precursors of the brain and the gastrula organizer. Previous findings suggested that the BCNE behaves as a homogeneous cell population that only depends on nuclear β-catenin activity but does not require Nodal and later segregates into its descendants during gastrulation. In contrast to previous findings, in this work, we show that the BCNE does not behave as a homogeneous cell population in response to Nodal antagonists. In fact, we found that chordin.1 expression in a marginal subpopulation of notochordal precursors indeed requires Nodal input. We also establish that an animal BCNE subpopulation of cells that express both, chordin.1 and sox2 (a marker of pluripotent neuroectodermal cells), and gives rise to most of the brain, persisted at blastula stage after blocking Nodal. Therefore, Nodal signaling is required to define a population of chordin.1+ cells and to restrict the recruitment of brain precursors within the BCNE as early as at blastula stage. We discuss our findings in Xenopus in comparison to other vertebrate models, uncovering similitudes in early brain induction and delimitation through Nodal signaling.This article has an associated First Person interview with the first author of the paper.


2020 ◽  
Author(s):  
Aitana M. Castro Colabianchi ◽  
María B. Tavella ◽  
Laura E. Boyadjián López ◽  
Marcelo Rubinstein ◽  
Lucía F. Franchini ◽  
...  

ABSTRACTThe Blastula Chordin- and Noggin Expressing Center (BCNE) comprises animal-dorsal and marginal-dorsal cells of the amphibian blastula and contains the precursors of the brain and of the gastrula organizer. Previous findings suggested that the BCNE behaves as a homogeneous cell population that depends only on nuclear β-catenin activity but does not require Nodal and segregates into its descendants later, during gastrulation. In this work, we analyzed if the BCNE is already compartmentalized at the blastula stage. In contrast to previous findings, we show that the BCNE does not behave as a homogeneous cell population in response to Nodal antagonists. In fact, we found that the chordin.1 expression in a marginal subpopulation of notochordal precursors indeed requires Nodal input. We also establish that an animal BCNE subpopulation of cells that express both, chordin.1 and sox2 (a marker of pluripotent neuroectodermal cells), and gives rise to most of the brain, persisted at blastula stage after blocking Nodal. Moreover, RT-qPCR analysis showed that chordin.1 and sox2 expression increased at blastula stage after blocking Nodal. Therefore, Nodal signaling is required to define a population of chordin.1+ cells and to restrict the recruitment of brain precursors within the BCNE as early as at blastula stage.


Cellulose ◽  
2018 ◽  
Vol 25 (12) ◽  
pp. 7299-7314 ◽  
Author(s):  
Hyo Jeong Kim ◽  
Dongyeop X. Oh ◽  
Seunghwan Choy ◽  
Hoang-Linh Nguyen ◽  
Hyung Joon Cha ◽  
...  

2019 ◽  
Author(s):  
Lorenz Adlung ◽  
Paul Stapor ◽  
Christian Tönsing ◽  
Leonard Schmiester ◽  
Luisa E. Schwarzmüller ◽  
...  

SummarySurvival or apoptosis is a binary decision in individual cells. Yet, at the cell population level, a graded increase in survival of CFU-E cells is observed upon stimulation with Erythropoietin (Epo). To identify components of JAK2/STAT5 signal transduction that contribute to the graded population response, a cell population-level model calibrated with experimental data was extended to study the behavior in single cells. The single-cell model showed that the high cell-to-cell variability in nuclear phosphorylated STAT5 is caused by variability in the amount of EpoR:JAK2 complexes and of SHP1 as well as the extent of nuclear import due to the large variance in the cytoplasmic volume of CFU-E cells. 24 to 118 pSTAT5 molecules in the nucleus for 120 min are sufficient to ensure cell survival. Thus, variability in membrane-associated processes are responsible to convert a switch-like behavior at the single-cell level to a graded population level response.HighlightsMathematical modeling enables integration of heterogeneous dataSingle-cell modeling captures binary decision processMultiple sources of cell-to-cell variability in erythroid progenitor cellsMinimal amount of active STAT5 sufficient for survival of erythroid progenitor cells


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