scholarly journals Single-cell landscapes of primary glioblastomas and matched organoids and cell lines reveal variable retention of inter- and intra-tumor heterogeneity

2021 ◽  
Author(s):  
VG LeBlanc ◽  
DL Trinh ◽  
S Aslanpour ◽  
M Hughes ◽  
D Livingstone ◽  
...  

SummaryGlioblastomas (GBMs) are aggressive primary malignant brain tumors characterized by extensive levels of inter- and intra-tumor genetic and phenotypic heterogeneity. Patient-derived organoids (PDOs) have recently emerged as useful models to study such heterogeneity. Here, we present bulk exome as well as single-cell genome and transcriptome profiles of primary IDH wild type GBMs from ten patients, including two recurrent tumors, as well as PDOs and brain tumor-initiating cell (BTIC) lines derived from these patients. We find that PDOs are genetically similar to and variably retain gene expression characteristics of their parent tumors. At the phenotypic level, PDOs appear to exhibit similar levels of transcriptional heterogeneity as their parent tumors, whereas BTIC lines tend to be enriched for cells in a more uniform transcriptional state. The datasets introduced here will provide a valuable resource to help guide experiments using GBM-derived organoids, especially in the context of studying cellular heterogeneity.

2021 ◽  
Author(s):  
Gabriel H. Negreira ◽  
Pieter Monsieurs ◽  
Hideo Imamura ◽  
Ilse Maes ◽  
Nada Kuk ◽  
...  

Leishmania, a unicellular eukaryotic parasite, is a unique model for aneuploidy and cellular heterogeneity, along with their potential role in adaptation to environmental stresses. Somy variation within clonal populations was previously explored in a small subset of chromosomes using fluorescence hybridization methods. This phenomenon, termed mosaic aneuploidy (MA) might have important evolutionary and functional implications, but remains under-explored due to technological limitations. Here, we applied and validated a high throughput single-cell genome sequencing method to study for the first time the extent and dynamics of whole karyotype heterogeneity in two Leishmania clonal populations representing different stages of MA evolution in vitro. We found that drastic changes in karyotypes quickly emerge in a population stemming from an almost euploid founder cell. This possibly involves polyploidization/hybridization at an early stage of population expansion, followed by assorted ploidy reduction. During further stages of expansion, MA increases by moderate and gradual karyotypic alterations. MA usually affected a defined subset of chromosomes, of which some display enrichment in snoRNA genes which could represent an adaptative benefit to the amplification of these chromosomes. Our data provide the first complete characterization of MA in Leishmania and pave the way for further functional studies.


2018 ◽  
Vol 6 (19) ◽  
pp. e00383-18 ◽  
Author(s):  
David K. Ngugi ◽  
Ulrich Stingl

ABSTRACT Candidate division SA1 encompasses a phylogenetically coherent archaeal group ubiquitous in deep hypersaline anoxic brines around the globe. Recently, the genome sequences of two cultivated representatives from hypersaline soda lake sediments were published. Here, we present a single-cell genome sequence from Nereus Deep in the Red Sea that represents a putatively novel family within SA1.


Author(s):  
S. Bhattacharya ◽  
J. Lillis ◽  
C. Baker ◽  
M. Guo ◽  
J.R. Myers ◽  
...  

2018 ◽  
Vol 9 ◽  
Author(s):  
Zachary C. Landry ◽  
Kevin Vergin ◽  
Christopher Mannenbach ◽  
Stephen Block ◽  
Qiao Yang ◽  
...  

2015 ◽  
Vol 81 (22) ◽  
pp. 7860-7868 ◽  
Author(s):  
Jacob H. Munson-McGee ◽  
Erin K. Field ◽  
Mary Bateson ◽  
Colleen Rooney ◽  
Ramunas Stepanauskas ◽  
...  

ABSTRACTNanoarchaeotaare obligate symbionts with reduced genomes first described from marine thermal vent environments. Here, both community metagenomics and single-cell analysis revealed the presence ofNanoarchaeotain high-temperature (∼90°C), acidic (pH ≈ 2.5 to 3.0) hot springs in Yellowstone National Park (YNP) (United States). Single-cell genome analysis of two cells resulted in two nearly identical genomes, with an estimated full length of 650 kbp. Genome comparison showed that these two cells are more closely related to the recently proposedNanobsidianus stetterifrom a more neutral YNP hot spring than to the marineNanoarchaeum equitans. Single-cell and catalyzed reporter deposition-fluorescencein situhybridization (CARD-FISH) analysis of environmental hot spring samples identified the host of the YNPNanoarchaeotaas aSulfolobalesspecies known to inhabit the hot springs. Furthermore, we demonstrate thatNanoarchaeotaare widespread in acidic to near neutral hot springs in YNP. An integrated viral sequence was also found within oneNanoarchaeotasingle-cell genome and further analysis of the purified viral fraction from environmental samples indicates that this is likely a virus replicating within the YNPNanoarchaeota.


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