Single-cell RNA-seq reveals a distinct transcriptome signature of aneuploid hematopoietic cells

Zhao, Xin; Gao, Shaojian; Wu, Zhijie; Kajigaya, Sachiko; Feng, Xingmin; Liu, Qingguo; Townsley, Danielle M.; Cooper, James N.; Chen, Jinguo; Keyvanfar, Keyvan; Ibanez, Maria del Pilar Fernandez; Wang, Xujing; Young, Neal S.

doi:10.1182/blood-2017-08-803353

Cited by 54 publications

(56 citation statements)

References 56 publications

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“…In aneuploid mouse embryonic fibroblast cell lines, the RNA expression from the gained chromosomes was also found to be overall proportional to chromosome copy numbers (Williams et al, 2008). Similar observations were also made in human monosomy 7 myeloid malignancies in a recent single-cell RNA sequencing analysis (Zhao et al, 2017). …”

Section: Effects Of Aneuploidy On Gene Expressionsupporting

confidence: 80%

Cellular Stress Associated with Aneuploidy

et al. 2018

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Aneuploidy, chromosome stoichiometry that deviates from exact multiples of the haploid compliment of an organism, exists in eukaryotic microbes, several normal human tissues, and the majority of solid tumors. Here, we review the current understanding about the cellular stress states that may result from aneuploidy. The topics of aneuploidy-induced proteotoxic, metabolic, replication, and mitotic stress are assessed in the context of the gene dosage imbalance observed in aneuploid cells. We also highlight emerging findings related to the downstream effects of aneuploidy-induced cellular stress on the immune surveillance against aneuploid cells.

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Section: Effects Of Aneuploidy On Gene Expressionsupporting

confidence: 80%

Cellular Stress Associated with Aneuploidy

et al. 2018

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“…This was confirmed in single hematopoietic stem/progenitor cells (HSPCs) using single-cell RNA sequencing. 44 Thus, significant reduction of expression levels is not a useful indicator in searching for or evaluating them.…”

Section: New Approachesmentioning

confidence: 99%

The enigma of monosomy 7

Inaba

Honda

Matsui

2018

Blood

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Since a report of some 50 years ago describing refractory anemia associated with group C monosomy, monosomy 7 (-7) and interstitial deletions of chromosome 7 (del(7q)) have been established as one of the most frequent chromosomal aberrations found in essentially all types of myeloid tumors regardless of patient age and disease etiology. In the last century, researchers sought recessive myeloid tumor-suppressor genes by attempting to determine commonly deleted regions (CDRs) in del(7q) patients. However, these efforts were not successful. Today, tumor suppressors located in 7q are believed to act in a haploinsufficient fashion, and powerful new technologies such as microarray comparative genomic hybridization and high-throughput sequencing allow comprehensive searches throughout the genes encoded on 7q. Among those proposed as promising candidates, 4 have been validated by gene targeting in mouse models. (sterile α motif domain 9) and (SAMD9-like) encode related endosomal proteins, mutations of which cause hereditary diseases with strong propensity to infantile myelodysplastic syndrome (MDS) harboring monosomy 7. Because MDS develops in -deficient mice over their lifetime,/ are likely responsible for sporadic MDS with -7/del(7q) as the sole anomaly. (enhancer of zeste homolog 2) and (mixed lineage leukemia 3) encode histone-modifying enzymes; loss-of-function mutations of these are detected in some myeloid tumors at high frequencies. In contrast to /, loss of or likely contributes to myeloid tumorigenesis in cooperation with additional specific gene alterations such as of or genes involved in the p53/Ras pathway, respectively. Distinctive roles with different significance of the loss of multiple responsible genes render the complex nature of myeloid tumors carrying -7/del(7q).

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“…Therefore, in the present study, only patient B cells from BM were used in the following analyses. Marker-based classification of cell subpopulations from patient B. CD34, CD38, mast/stem cell growth factor receptor Kit (KIT or CD117) and HLA-DRA have been used to sort LSCs or hematopoietic stem/progenitor cells in different leukemia samples (41)(42)(43)(44). Therefore, these four markers were selected to broadly classify the cell sub-populations from patient B.…”

Section: Resultsmentioning

confidence: 99%

Single‑cell RNA sequencing of t(8;21) acute myeloid leukemia for risk prediction

Xiong

Huang

et al. 2020

Oncol Rep

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Single-cell RNA sequencing (scRNA-seq) of bone marrow or peripheral blood samples from patients with acute myeloid leukemia (AML) enables the characterization of heterogeneous malignant cells. A total of 87 cells from two patients with t(8;21) AML were analyzed using scRNA-seq. Clustering methods were used to separate leukemia cells into different sub-populations, and the expression patterns of specific marker genes were used to annotate these populations. Among the 31 differentially expressed genes in the cells of a patient who relapsed after hematopoietic stem cell transplantation, 13 genes were identified to be associated with leukemia. Furthermore, three genes, namely AT-rich interaction domain 2, lysine methyltransferase 2A and synaptotagmin binding cytoplasmic RNA interacting protein were validated as possible prognostic biomarkers using two bulk expression datasets. Taking advantage of scRNA-seq, the results of the present study may provide clinicians with several possible biomarkers to predict the prognostic outcomes of t(8;21) AML.

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Single-cell RNA-seq reveals a distinct transcriptome signature of aneuploid hematopoietic cells

Abstract: Key Points We distinguished aneuploid cells from diploid cells within the hematopoietic stem and progenitor cells using scRNA-seq. Monosomy 7 cells showed downregulated pathways involved in immune response and maintenance of DNA stability.

Cited by 54 publications

References 56 publications

Cellular Stress Associated with Aneuploidy

Cellular Stress Associated with Aneuploidy

The enigma of monosomy 7

Single‑cell RNA sequencing of t(8;21) acute myeloid leukemia for risk prediction

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