Single-Cell RNA-seq Reveals Characteristics of Malignant Cells and Immune Microenvironment in Subcutaneous Panniculitis-Like T-Cell Lymphoma

Li, Zifeng; Wang, Hongsheng; Dong, Rui; Man, J. C. H. de; Sun, Li; Qian, Xiaowen; Zhu, Xiaohua; Cao, Ping; Yu, Yi; Le, Jie; Fu, Yang Xin; Wang, Ping; Jiang, Wenjin; Shen, Chen; Ma, Yangyang; Chen, Lian; Xu, Yaochen; Shi, Jiantao; Zhang, Hui; Qian, Maoxiang; Zhai, Xiaowen

doi:10.3389/fonc.2021.611580

Cited by 9 publications

(12 citation statements)

References 38 publications

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“…RUNX1 and GATA2 are essential for normal megakaryopoiesis ( 7 ). ELF1 (E74-like ETS transcription factor 1) is one the top 10 transcriptional factors (TFs) among MKs ( 5 ) in yolk sac (YS), which warrants further research. Experiments showed that platelet factor 4 ( PF4 ), an inhibitor of megakaryopoiesis ( 8 ), is regulated by ELF1 ( 9 ).…”

Section: Resultsmentioning

confidence: 99%

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Revealing the intratumoral heterogeneity of non-DS acute megakaryoblastic leukemia in single-cell resolution

Li²,

Yang³

et al. 2022

Front. Oncol.

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Pediatric acute megakaryoblastic leukemia (AMKL) is a subtype of acute myeloid leukemia (AML) characterized by abnormal megakaryoblasts, and it is divided into the AMKL patients with Down syndrome (DS-AMKL) and AMKL patients without DS (non-DS-AMKL). Pediatric non-DS-AMKL is a heterogeneous disease with extremely poor outcome. We performed single-cell RNA sequencing (scRNA-seq) of the bone marrow from two CBFA2T3-GLIS2 fusion-positive and one RBM15-MKL1 fusion-positive non-DS-AMKL children. Meanwhile, we downloaded the scRNA-seq data of normal megakaryocyte (MK) cells of the fetal liver and bone marrow from healthy donors as normal controls. We conducted cell clustering, cell-type identification, inferCNV analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and Monocle2 analysis to investigate the intratumoral heterogeneity of AMKL. Using canonical markers, we identified and characterized the abnormal blasts and other normal immune cells from three AMKL samples. We found intratumoral heterogeneity of AMKL in various cell-type proportions, malignant cells’ diverse copy number variations (CNVs), maturities, significant genes expressions, and enriched pathways. We also identified potential markers for pediatric AMKL, namely, RACK1, ELOB, TRIR, NOP53, SELENOH, and CD81. Our work offered insight into the heterogeneity of pediatric acute megakaryoblastic leukemia and established the single-cell transcriptomic landscape of AMKL for the first time.

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Section: Resultsmentioning

confidence: 99%

“…Most previous studies were transcriptional profiling of AMKL, which undermined the heterogeneity of tumors. Recently, single-cell RNA sequencing (scRNA-seq) was performed in numerous cancers to study the intratumoral heterogeneity, developing trajectory, and immune microenvironment ( 5 , 6 ).…”

Section: Introductionmentioning

confidence: 99%

Revealing the intratumoral heterogeneity of non-DS acute megakaryoblastic leukemia in single-cell resolution

Li²,

Yang³

et al. 2022

Front. Oncol.

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“…Thus, targeting of the TIM-4-AMPKa1 interaction would be effective to augment antitumor immunity and improve cancer chemotherapy ( 20 ). Recently, it has been reported that TIM-4 is specifically expressed in subcutaneous panniculitis T-cell lymphoma (SPTCL) malignant cells, indicating that TIM-4 may be a potential novel marker for SPTCL ( 34 ).Indeed, TIM-4 has been reported as a potential target for cancer diagnosis and therapy ( 35 ).Besides, TIM-4 is detected in several kinds of cancer including glioma, colorectal cancer, parapharyngeal liposarcoma, and so on. Consistently, our studies show that the expression of TIM-4 in NSCLC is significantly higher than adjacent tissues and increased expression of TIM-4 promotes metastasis of NSCLC.…”

Section: Discussionmentioning

confidence: 99%

N-Glycosylation at Asn291 Stabilizes TIM-4 and Promotes the Metastasis of NSCLC

Chen

Wang

et al. 2022

Front. Oncol.

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T-cell immunoglobulin domain and mucin domain 4 (TIM-4) is a transmembrane protein that promotes epithelial-mesenchymal transition (EMT), migration and invasion of non-small cell lung cancer (NSCLC) cells. Most transmembrane proteins are modified by N-glycosylation and the importance of protein N-glycosylation in cancer cell metastasis has been well appreciated. However, whether TIM-4 is modified by N-glycosylation and the role of TIM-4 N-glycosylation in NSCLC remains largely unknown. In the current study, we reported that TIM-4 was extensively N-glycosylated at Asn291. After the removal of N-glycosylation, the stability of TIM-4 protein was decreased and TIM-4 was more susceptible to degradation by ER-localized ubiquitin ligase-mediated ERAD. Thus, the expression of TIM-4 on the cell surface was decreased, which suppressed TIM-4-mediated metastasis in NSCLC. In summary, the present study identifies TIM-4 N-glycosylation and its role in NSCLS migration, which would provide a valuable biomarker for developing drugs targeting N-glycosylation at Asn291 on TIM-4.

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“…Subcutaneous panniculitis-like T-cell lymphoma (SPTcL) is a malignant primary T-cell lymphoma. delay in diagnosis and a high misdiagnosis rate affect the prognosis and survival of patients (83). Through single-cell RNA sequencing, TIM-4 was identified as a potential novel marker for SPTCL, which was specifically differentially expressed in the SPTCL cells.…”

Section: Regulatory Role Of Tim-4 In the Occurrence And Development O...mentioning

confidence: 99%

“…Through single-cell RNA sequencing, TIM-4 was identified as a potential novel marker for SPTCL, which was specifically differentially expressed in the SPTCL cells. This offers insight into the heterogeneity of SPTcL (83). TIM-4 is involved in a variety of cellular biological functions of tumor cells.…”

Section: Regulatory Role Of Tim-4 In the Occurrence And Development O...mentioning

confidence: 99%

Function and characteristics of TIM‑4 in immune regulation and disease (Review)

Wang

Chen

et al. 2022

Int J Mol Med

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T-cell/transmembrane immunoglobulin and mucin domain containing 4 (TIM-4) is a phosphatidylserine receptor that is mainly expressed on antigen-presenting cells and is involved in the recognition and efferocytosis of apoptotic cells. TIM-4 has been found to be expressed in immune cells such as natural killer T, B and mast cells and to participate in multiple aspects of immune regulation, suggesting that TIM-4 may be involved in a variety of immune-related diseases. Recent studies have confirmed that TIM-4 is also abnormally expressed in a variety of malignant tumor cells and is closely associated with the occurrence and development of tumors and the tumor immune microenvironment. The present study aimed to describe the expression and functional characteristics of TIM-4 in detail and to comprehensively discuss its role in pathophysiological processes such as infection, allergy, metabolism, autoimmunity and tumor immunity. The current review provided a comprehensive understanding of the functions and characteristics of TIM-4, as well as novel ideas for the diagnosis and treatment of diseases. Contents 1. Introduction 2. Regulatory role of TIM-4 in efferocytosis 3. Functional characteristics of TIM-4 in different immune cells 4. Regulatory role of TIM-4 in the occurrence and development of diseases 5. conclusion

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Single-Cell RNA-seq Reveals Characteristics of Malignant Cells and Immune Microenvironment in Subcutaneous Panniculitis-Like T-Cell Lymphoma

Cited by 9 publications

References 38 publications

Revealing the intratumoral heterogeneity of non-DS acute megakaryoblastic leukemia in single-cell resolution

Revealing the intratumoral heterogeneity of non-DS acute megakaryoblastic leukemia in single-cell resolution

N-Glycosylation at Asn291 Stabilizes TIM-4 and Promotes the Metastasis of NSCLC

Function and characteristics of TIM‑4 in immune regulation and disease (Review)

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