單細(xì)胞事業(yè)部 ｜ 歐易生物 V22.4.23

單細(xì)胞事業(yè)部 ｜ 歐易生物 V22.5 1

目 錄

一、疾病發(fā)展與機(jī)理

Targeting Degradation of the Transcription Factor C/EBPβ Reduces Lung Fibrosis by Restoring Activity of the

Ubiquitin-Editing Enzyme A20 in Macrophages……………………………………………………………………...... 5

Single-cell RNA sequencing highlights the role of inflammatory cancer-associated fibroblasts in bladder urothelial

carcinoma……………………………………………………………………………………………………………….. 8

Mesenchymal stem cells alleviate LPS-induced acute lung injury by inhibiting the proinflammatory function of Ly6C+

CD8+ T cells………………………………………………………………………………………………..................... 11

Immunosuppressive effects of mesenchymal stem cells on lung B cell gene expression in LPS-induced acute lung

injury……………………………………………………………………………………………………………………. 13

The T Cell Receptor Immune Repertoire Protects the Liver from Reconsitution……………………………………… 14

Mesenchymal stem cell-mediated immunomodulation of recruited mononuclear phagocytes during acute lung injury:

a high-dimensional analysis study.………………………………………………………………………….................... 18

Pathogenesis study based on high throughput single-cell sequencing analysis reveals novel transcriptional landscape

and heterogeneity of retinal cells in type 2 diabetic mice………………………………………………………………. 20

Single-cell transcriptomic analysis of eutopic endometrium and ectopic lesions of adenomyosis…………………….. 22

Phenotyping of immune and endometrial epithelial cells in endometrial carcinomas revealed by single-cell RNA

sequencing………………………………………………………………………………………………………………. 23

Study on the clinical mechanism of Tong-Xie-An-Chang Decoction in the treatment of diarrheal irritable bowel

syndrome based on single-cell sequencing technology…………………………………………………………………. 26

Single-cell transcriptomic analyses of cardiac immune cells reveal that Rel-driven CD72-positive macrophages induce

cardiomyocyte injury…………………………………………………………………………………………………… 29

Single-cell transcriptomic analysis of endometriosis provides insights into fibroblast fates and immune cell

heterogeneity……………………………………………………………………………………………………………. 31

Single-cell RNA sequencing reveals the cell landscape of a radiation-induced liver injury mouse model……………. 41

Islet β-cells physiological difference study of old and young mice based on single-cell transcriptomics……………….. 43

Stroke subtype-dependent synapse elimination by reactive gliosis in mice……………………………………………... 44

Single-Cell RNA-Seq of Bone Marrow Cells in Aplastic Anemia.……………………………………………………... 45

Single-cell RNA sequencing reveals B cell–related molecular biomarkers for Alzheimer’s disease…………………… 47

From nasal to basal: single-cell sequencing of the bursa of Fabricius highlights the IBDV infection mechanism in

chickens…………………………………………………………………………………………………………………. 48

LKB1 dificiency upregulates RELM-α to drive airway goblet cell metaplasia…………………………………………. 49

Systematic search for schizophrenia pathways sensitive to perturbation by immune activation……………………....... 51

Low XIST expression in Sertoli cells of Klinefelter syndrome patients caused the high susceptibility of these cells to

an extra X chromosome…………………………………………………………………………………………………. 52

Dihydroartemisinin Shows Promising Effects in the Treatment of Experimental Autoimmune Encephalomyelitis and

Maintains In§ammatory Homeostasis by Targeting AXL in Microglia…………………………………………………. 53

Single-Cell RNA Sequencing of the Rat Carotid Arteries Uncovers Potential Cellular Targets of Neointimal

Hyperplasia……………………………………………………………………………………………………………... 54

Single-Cell RNA Sequencing Reveals the Temporal Diversity and Dynamics of Cardiac Immunity after Myocardial

Infarction………………………………………………………………………………………………………………... 55

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Coal dust exposure triggers heterogeneity of transcriptional profiles in mouse pneumoconiosis and Vitamin D

remedies………………………………………………………………………………………………………………… 56

Heterogeneity of human corneal endothelium implicates lncRNA NEAT1 in Fuchs endothelial corneal dystrophy…… 57

Single-Cell RNA-Seq Analysis Reveals Macrophage Involved in the Progression of Human Intervertebral Disc

Degeneration……………………………………………………………………………………………………………. 63

Integrated hepatic single-cell RNA sequencing and untargeted metabolomics reveals the immune and metabolic

modulation of Qing-Fei-Pai-Du decoction in mice with coronavirus-induced pneumonia……………………………… 65

Single-cell RNA-sequencing analysis reveals the molecular mechanism of subchondral bone cell heterogeneity in the

development of osteoarthritis…………………………………………………………………………………………… 66

Maintaining hypoxia environment of subchondral bone alleviates 2 osteoarthritis progression……………………........ 68

EP3 enhances adhesion and cytotoxicity of NK cells toward hepatic stellate cells in a murine liver fibrosis model…..... 71

Single-Cell Sequencing of Immune Cells in Human Aortic Dissection Tissue Provides Insights Into Immune Cell

Heterogeneity…………………………………………………………………………………………………………… 74

Single-Cell RNA Sequencing Reveals Heterogeneity of Myf5-Derived Cells and Altered Myogenic Fate in the

Absence of SRSF2………………………………………………………………………………………………………. 76

二、 腫瘤微環(huán)境

Characteristics of a novel cell line ZJU-0430 established from human gallbladder carcinoma…………………………. 6

Combinatorial Photothermal 3D‐Printing Scaffold and Checkpoint Blockade Inhibits Growth/Metastasis of Breast

Cancer to Bone and Accelerates Osteogenesis………………………………………………………………………...... 7

Single-cell analysis of developing and azoospermia human testicles reveals central role of Sertoli cells……………..… 9

Single-cell transcriptome atlas of lung adenocarcinoma featured with ground glass nodules…………………………… 12

Identification of differentially expressed genes in lung adenocarcinoma cells using single-cell RNA sequencing not

detected using traditional RNA sequencing and microarray…………………………………………………………...... 16

Ligand-receptor interaction atlas within and between tumor cells and T cells in lung adenocarcinoma……………...…. 17

Landscape and dynamics of single tumor and immune cells in early and advanced-stage lung adenocarcinoma……...... 19

Blinatumomab-induced T cell activation at single cell transcriptome resolution……………………………………....... 24

Dissecting the single-cell transcriptome network underlying esophagus non-malignant tissues and esophageal

squamous cell carcinoma……………………………………………………………………………………………....... 30

Topological analysis of hepatocellular carcinoma tumour microenvironment based on imaging mass cytometry reveals

cellular neighbourhood regulated reversely by macrophages with different ontogeny……………………….................. 32

Single-cell transcriptomes reveal heterogeneity of high-grade serous ovarian carcinoma………………………………. 33

Single-Cell Transcriptomics of Glioblastoma Reveals a Unique Tumor Microenvironment and Potential

Immunotherapeutic Target Against Tumor-Associated Macrophage…………………………………………………… 34

Pro-inflammatory and proliferative microglia drive progression of glioblastoma………………………………………. 35

Visualization of endogenous p27 and Ki67 reveals the importance of a c-Myc-driven metabolic switch in promoting

survival of quiescent cancer cells……………………………………………………………………………………...... 36

Dissecting the single-cell transcriptome network in patients with esophageal squamous cell carcinoma receiving

operative paclitaxel plus platinum chemotherapy……………………………………………………………………….. 37

A case study of relapsed and refractory multiple myeloma reveals clonal evolution and gene regulatory networks of

plasma cells via combining consecutive genomics with single-cell transcriptomes…………………………………...... 39

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5mC regulator-mediated molecular subtypes depict the hallmarks of the tumor microenvironment and guide precision

medicine in bladder cancer……………………………………………………………………………………………… 40

Dissecting the heterogeneity of the microenvironment in primary and recurrent nasopharyngeal carcinomas using

single-cell RNA sequencing…………………………………………………………………………………………...... 59

Single-Cell Transcriptomes Combining with Consecutive Genomics Reveal Clonal Evolution and Gene Regulatory

Networks in Relapsed and Refractory Multiple Myeloma………………………………………………………………. 67

Single-cell and spatial analysis reveal interaction of FAP+ fibroblasts and SPP1+ macrophages in colorectal cancer….. 69

Hepatocellular carcinoma-infiltrating γδ T cells are functionally defected and allogenic Vδ2+ γδ T cell can be a

promising complement………………………………………………………………………………………………...... 70

Cisplatin resistance-related multi-omics differences and the establishment of machine learning models………………. 72

miR-6077 promotes cisplatin/pemetrexed resistance in lung adenocarcinoma via CDKN1A/ cell cycle arrest and

KEAP1/ferroptosis pathways…………………………………………………………………………………………… 73

Exploring the R-ISS stage-specific regular networks in the progression of multiple myeloma at single-cell resolution 75

三、 細(xì)胞圖譜

Single-cell transcriptomes of mouse bladder urothelium uncover novel cell type markers and urothelial differentiation

characteristics…………………………………………………………………………………………………………… 21

Transcriptomic Profiling of Human Placenta in Gestational Diabetes Mellitus at the Single-Cell Level……………...... 27

Molecular identity of human limbal heterogeneity involved in corneal homeostasis and privilege…………………….. 28

The histone demethylase Kdm6b regulates the maturation and cytotoxicity of TCRαβ+CD8αα+ intestinal

intraepithelial lymphocytes……………………………………………………………………………………………... 38

Single-Cell RNA Sequencing of Mouse Left Ventricle Reveals Cellular Diversity and Intercommunication………....... 42

Single-cell RNA-seq and chromatin accessibility profiling decipher the heterogeneity of mouse γ δ T cells…………… 46

Single-Cell Transcriptome Atlas of Human Mesenchymal Stem Cells Exploring Cellular Heterogeneity……………... 50

四、 生長發(fā)育

scRNA-seq of ovarian follicle granulosa cells from different fertility goats reveals distinct expression patterns……….. 25

Molecular identity of human limbal heterogeneity involved in corneal homeostasis and privilege…………………… 28

From nasal to basal: single-cell sequencing of the bursa of Fabricius highlights the IBDV infection mechanism in

chickens…………………………………………………………………………………………………………………. 48

五、空間轉(zhuǎn)錄組

Transcriptome-scale spatial gene expression in rat arcuate nucleus during puberty……………………………….……. 58

Transcriptomic Mapping of Human Parotid Gland at Single-Cell Resolution…………………………………………... 64

Single-cell and spatial analysis reveal interaction of FAP+ fibroblasts and SPP1+ macrophages in colorectal cancer...... 69

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六、 植物單細(xì)胞

Global Dynamic Molecular Profiling of Stomatal Lineage Cell Development by Single-Cell RNA Sequencing………. 10

Single-Cell RNA Sequencing Efficiently Predicts Transcription Factor Targets in Plants……………………………… 15

Identification of Novel Regulators Required for Early Development of Vein Pattern in the Cotyledons by Single-cell

RNA-seq…………………………………………………………………………………………………………........... 60

Single-cell RNA sequencing reveals the landscape of maize root tips and assists in identification of cell type-specific

nitrate-response genes…………………………………………………………………………………………………... 61

Identification of the Regulators of Epidermis Development under Drought- and Salt-Stressed Conditions by SingleCell RNA-Seq…………………………………………………………………………………………………………... 62

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2019 年 IF：31.741

01

SUMMARY

Although recent progress provides mechanistic in- sights into the pathogenesis of pulmonary fibrosis

(PF), rare anti-PF therapeutics show definitive promise for treating this disease. Repeated lung

epithelial injury results in injury-repairing response and inflammation, which drive the development

of PF. Here, we report that chronic lung injury inactivated the ubiquitin-editing enzyme A20, causing

progressive accumulation of the transcription factor C/EBPb in alveolar macrophages (AMs) from PF

patients and mice, which upregulated a number of immunosuppressive and profibrotic factors

promoting PF development. In response to chronic lung injury, elevated glycogen synthase kinase-3b

(GSK-3b) interacted with and phosphorylated A20 to suppress C/EBPb degradation. Ectopic

expression of A20 or pharmacological restoration of A20 activity by disturbing the A20-GSK-3b

interaction accelerated C/EBPb degradation and showed potent therapeutic efficacy against

experimental PF. Our study indicates that a regulatory mechanism of the GSK-3b-A20-C/EBPb axis

in AMs may be a potential target for treating PF and fibroproliferative lung diseases.

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02

2019 年 IF：5.722

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03

2020 年 IF：18.808

Cancer metastases are the main causes for the high mortality of cancer. The current treatment modality for bone

metastasis of breast cancer is dominantly destructive, which urges the engineering of multifunctional biomaterials,

not only for eliminating primary/metastases tumors effectively but also for enhancing bone–tissue regeneration.

Herein, an immune adjuvant (R837)-loaded and niobium carbide (Nb2C) MXene-modified 3D-printing

biodegradable scaffold (BG@NbSiR) is designed and constructed to effectively treat bone metastasis of breast

cancer. The engineered BG@ NbSiR scaffold can eradicate primary tumors, activate the immune response, suppress

metastases, prevent tumor relapses (long-term immunological memory) by synergizing with checkpoint blockade

immunotherapy, and accelerate osteogenesis as evidenced by multiple in vivo murine models. In particular, singlecell sequencing (scRNA-seq) is employed to further determine the critical factors responding to BG@NbSiR

scaffold-based photothermia plus checkpoint blockade-combined immunotherapy.

Several gene functional terms are identified in both

tumor biology (including copy number variation) and

immune response, which further reveal the underlying

therapeutic mechanisms from the perspective of singlecell transcriptome. This work not only demonstrates the

promising clinical application potentials of

BG@NbSiR scaffold- based therapy against bone

metastasis of breast cancer, but also provides distinctive

avenues to optimize the design and construction of

multifunctional tissue-engineering biomaterials based

on single-cell genomes.

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04

Although substantial progress has been made in cancer

biology and treatment, clinical outcomes of bladder

carcinoma (BC) patients are still not satisfactory. The

tumor micro- environment (TME) is a potential target.

Here, by single-cell RNA sequencing on 8 BC tumor

samples and 3 para tumor samples, we identify 19

different cell types in the BC micro- environment,

indicating high intra-tumoral heterogeneity. We find

that tumor cells down regulated MHC-II molecules,

suggesting that the downregulated immunogenicity of

cancer cells may contribute to the formation of an

immunosuppressive microenvironment. We also find

that monocytes undergo M2 polarization in the tumor

region and differentiate. Fur- thermore, the LAMP3 +

DC subgroup may be able to recruit regulatory T cells,

potentially taking part in the formation of an

immunosuppressive TME. Through correlation

analysis using public datasets containing over 3000 BC

samples, we identify a role for inflammatory cancerassociated fibroblasts (iCAFs) in tumor progression,

which is significantly related to poor prognosis.

Additionally, we characterize a regulatory network

depending on iCAFs. These results could help

elucidate the protumor mechanisms of iCAFs. Our

results provide deep insight into cancer immunology

and provide an essential resource for drug discovery in

the future.

2020 年 IF：14.912

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05

Clinical efficacy of treatments against non-obstructive azoospermia (NOA), which affects 1% of men, are

currently limited by the incomplete understanding of NOA pathogenesis and normal spermatogenic

microenvironment. Here, we profile >80,000 human testicular single- cell transcriptomes from 10 healthy

donors spanning the range from infant to adult and 7 NOA patients. We show that Sertoli cells, which form

the scaffold in the testicular micro- environment, are severely damaged in NOA patients and identify the

roadmap of Sertoli cell maturation. Notably, Sertoli cells of patients with congenital causes (Klinefelter

syndrome and Y chromosome microdeletions) are mature, but exhibit abnormal immune responses, while

the cells in idiopathic NOA (iNOA) are physiologically immature. Furthermore, we find that inhibition of

Wnt signaling promotes the maturation of Sertoli cells from iNOA patients, allowing these cells to regain

their ability to support germ cell survival. We provide a novel perspective on the development of diagnostic

methods and therapeutic targets for NOA.

2020 年 IF：14.912

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06

2020 年 IF：13.163

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07

2020 年 IF：8.461

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08

2020 年 IF：10.844

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09

2020 年 IF：6.834

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10

2020 年 IF：7.561

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11

2020 年 IF：5.751

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12

Overview of the 1,159,219 single cells from eighteen tumor samples and seven normal samples. a, The sample

origin of the cells; b, The cell types identified by marker genes.

2020 年 IF：5.66

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13

2020 年 IF：6.58

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14

2021 年 IF：11.553

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2021 年 IF：11.494

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Diabetic retinopathy (DR) is the leading cause of acquired blindness in middle-aged people. The

complex pathology of DR is difficult to dissect, given the convoluted cytoarch- itecture of the

retina. Here, we performed single-cell RNA sequencing (scRNA-seq) of retina from a model of

type 2 diabetes, induced in leptin receptor–deficient (db/db) and control db/m mice, with the aim

of elucidating the factors mediating the pathogenesis of DR. We identified 11 cell types and

determined cell-type-specific expression of DR-associated loci via genome-wide association

study (GWAS)-based enrichment analysis. DR also impacted cell-type-specific genes and

altered cell-cell communica- tion. Based on the scRNA-seq results, retinaldehyde-bind- ing

protein 1 (RLBP1) was investigated as a promising therapeutic target for DR. Retinal RLBP1

expression was decreased in diabetes, and its overexpression in Mu€ller glia mitigated DRassociated neurovascular degenera- tion. These data provide a detailed analysis of the retina

under diabetic and normal conditions, revealing new in- sights into pathogenic factors that may

be targeted to treat DR and related dysfunctions.

2021 年 IF：9.463

16

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17

2021 年 IF：6.832

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2021 年 IF：7.134

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19

2021 年 IF：5.683

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2021 年 IF：3.694

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21

2021 年 IF：2.002

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2021 年 IF：1.881

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2021 年 IF：5.55

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2021 年 IF：5.032

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2021 年 IF：10.784

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2021 年 IF：8.142

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2021 年 IF：7.134

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2021 年 IF：23.051

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Abstract

Background: High-grade serous ovarian carcinoma (HGSOC) is the most com- mon and aggressive

histotype of epithelial ovarian cancer. The heterogeneity and molecular basis of this disease remain

incompletely understood.

Methods: To address this question, we have performed a single-cell transcrip- tomics analysis of

matched primary and metastatic HGSOC samples.

Results: A total of 13 571 cells are categorized into six distinct cell types, includ- ing epithelial cells,

fibroblast cells, T cells, B cells, macrophages, and endothe- lial cells. A subset of aggressive epithelial

cells with hyperproliferative and drug- resistant potentials is identified.

Several new markers that are highly expressed in

epithelial cells are characterized, and their roles in

ovarian cancer cell growth and migration are further

confirmed. Dysregulation of multiple signaling pathways, including the translational machinery, is

associated with ovarian cancer metastasis through the

trajectory analysis. Moreover, single-cell regulatory

net- work inference and clustering (SCENIC) analysis

reveals the gene regulatory net- works and suggests the

JUN signaling pathway as a potential therapeutic

target for treatment of ovarian cancer, which is

validated using the JUN/AP-1 inhibitor T-5224.

Finally, our study depicts the epithelial-fibroblast cell

communication atlas and identifies several important

receptor-ligand complexes in ovarian can- cer

development.

2021 年 IF：11.491

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30

2021 年 IF：6.244

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2021 年 IF：9.423

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32

2021 年 IF：11.552

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2021 年 IF：7.48

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2021 年 IF：15.824

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? Abstract

This study attempted to investigate how clonal structure evolves, along with potential regulatory networks, as a result

of multiline therapies in relapsed/refractory multiple myeloma (RRMM). Eight whole exome sequencing (WES) and

one single cell RNA sequencing (scRNA-seq) were performed in order to assess dynamic genomic changes in

temporal consecutive samples of one RRMM patient from the time of diagnosis to death (about 37 months). The 63-

year-old female patient who suffered from MM (P1) had disease progression (PD) nine times from July 2017 (newly

diagnosed (ND)) to Aug 2020 (death), and the force to drive branching-pattern evolution of malignant PCs was found

to be sustained. The mutant-allele tumor heterogeneity (MATH) and tumor mutation burden (TMB) initially exhibited

a downward trend, which was then upward throughout the course of the disease. Various somatic single nucleotide

variants (SNVs) that had disappeared after the previous treatment were observed to reappear in later stages.

Chromosomal instability (CIN) and homologous recombination deficiency (HRD) scores were observed to be

increased during periods of all progression, especially in the period of extramedullary plasmacytoma. Finally, in

combination with WES and scRNA-seq of P1-PD9 (the nineth PD), the intro-heterogeneity and gene regulatory

networks of MM cells were deciphered. As verified by the overall survival of MM patients in the MMRF CoMMpass

and GSE24080 datasets, RUNX3 was identified as a potential driver for RRMM.

2021 年 IF：6.684

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36

2021 年 IF：8.772

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2021 年 IF：

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38

ABSTRACT

Previous studies have revealed the diversity of the whole cardiac cellulome but not refined the left ventricle, which

was essential for finding therapeutic targets. Here, we characterized single-cell transcriptional profiles of the

mouse left ventricular cellular landscape using single-cell RNA sequencing (10×Genomics). Detailed tDistributed Stochastic Neighbor Embedding (tSNE) analysis revealed the cell types of left ventricle with gene

markers. Left ventricular cellulome contained cardiomyocytes highly expressed Trdn, endothelial cells highly

expressed Pcdh17, fibroblast highly expressed Lama2 and macrophages highly expressed Hpgds, also proved by

in situ hybridization. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG)

enrichment analysis (ListHits>2, p<0.05) were employed with the DAVID database to investigate subtypes of

each cell type with the underlying functions of differentially expressed genes (DEGs). Endothelial cells included

five subtypes, fibroblasts comprised of seven subtypes and macrophages contained eleven subtypes. The key

representative DEGs (p<0.001) were Gja4 and Gja5 in cluster 3 of endothelial cells, Aqp2 and Thbs4 in cluster 2

of fibroblasts, as well as Clec4e and Trem-1 in in cluster 3 of marcophages perhaps involved in the occur of

atherosclerosis, heart failure and acute myocardial infarction proved by literature review. We also revealed

extensive networks of intercellular communication in left ventricle. We suggested possible therapeutic targets for

cardiovascular disease and autocrine and paracrine signaling underpins left ventricular homeostasis. This study

provided new insights into the structure and function of the mammalian left ventricular cellulome and offers an

important resource that will stimulate studies in cardiovascular research.

2021 年 IF：3.445

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2021 年 IF：4.232

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40

The pathological role of reactive gliosis in CNS repair remains controversial. In this study, using murine ischemic

and hemorrhagic stroke models, we demonstrated that microglia/ macrophages and astrocytes are differentially

involved in engulfing synapses in the reactive gliosis region. By specifically deleting MEGF10 and MERTK

phagocytic receptors, we deter- mined that inhibiting phagocytosis of microglia/macrophages or astrocytes in

ischemic stroke improved neurobehavioral outcomes and attenuated brain damage. In hemorrhagic stroke, inhibiting

phagocytosis of microglia/macrophages but not astrocytes improved neu- robehavioral outcomes. Single-cell RNA

sequencing revealed that phagocytosis related bio- logical processes and pathways were downregulated in astrocytes

of the hemorrhagic brain compared to the ischemic brain. Together, these findings suggest that reactive microgliosis

and astrogliosis play individual roles in mediating synapse engulfment in pathologically dis- tinct murine stroke

models and preventing this process could rescue synapse loss.

2021 年 IF：14.912

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2021 年 IF：4.59

Aplastic anemia (AA) is an autoimmune disease characterized by peripheral blood pancytopenia and bone marrow

failure. Recently, a research study verified bone marrow failure of AA patients resulting from hematopoietic stem and

progenitor cell (HSPC) attack by active T cells. Nonetheless, whether B cells, as one of the important immune cells,

destruct the hematopoiesis is still unclear. Here, a large-scale single-cell transcriptomic sequencing of 20,000 bone

marrow cells from AA patients and healthy donors was performed. A total of 17 clusters and differentially expressed

genes were identified in each cluster relative to other clusters, which were considered potential marker genes in each

cluster. The top differentially expressed genes in HSPCs (S100A8, RETN, and TNFAIP3), monocytes (CXCL8, JUN,

and IL1B), and neutrophils and granulocytes (CXCL8, NFKBIA, and MT-CYB) were related to immune and

inflammatory injury. Then, the B-cell receptor (BCR) diversities and pairing frequencies of V and J genes were analyzed.

The highest pairing frequencies in AA patients were IGHV3-20-IGKJ2, IGHV3-20-IGKJ4, and IGHV3-20-IGHLJ2.

Meanwhile, there were 3 V genes, including IGHV3-7, IGHV3-33, and IGLV2-11, with elevated expression in B cells

from AA patients. Cell type–specific ligand–receptor was further identified in B-cell interaction with hematopoietic cells

in the bone marrow. The changed ligand–receptor pairs involved antigen presentation, inflammation, apoptosis, and

proliferation of B cells. These data showed the transcriptomic landscape of hematopoiesis in AA at single-cell resolution,

providing new insights into hematopoiesis failure related with aberrance of B cells, and provide available targets of

treatment for AA.

Keywords: aplastic anemia, bone marrow, stem cell, BCR, single-cell RNA-seq

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42

ABSTRACT

The distinct characteristics of cd T cells determine their vital roles in the formation of local immune

responses and contribute to tissue homeostasis. However, the heterogeneity of cd T cells across tissues

remains unclear. By combining transcriptional and chromatin analyses with a truly unbiased fashion, we

constructed a single-cell transcriptome and chromatin accessibility landscape of mouse cd T cells in the

lymph, spleen, and thymus. We also revealed the heterogeneity of cd T1 and cd T17 cells across these

tissues and inferred their potential regulatory mechanisms. In the thymus, we reconstructed the

developmental trajectory and gained further insights into the signature genes from the mature stage,

intermediate stage, and immature stage of cd T cells on the basis of single-cell RNA sequencing and

single-cell assay for transposase-accessible chromatin sequencing data. Notably, a novel Gzma+ cd T cell

subset was identified with immature properties and only localized to the thymus. Finally, NR1D1, a

circadian transcription factor (TF), was validated as a key and negative regulator of cd T17 cell

differentiation by performing a combined analysis of TF motif enrichment, regulon enrichment, and

Nr1d1 knockout mice. In summary, our data represent a comprehensive mapping on the transcriptome

and chromatin accessibility dynamics of mouse cd T cells, providing a valuable resource and reference

for future studies on cd T cells.

2021 年 IF：11.78

單細(xì)胞事業(yè)部 ｜ 歐易生物 V22.5 47

43

2021 年 IF：8.718

單細(xì)胞事業(yè)部 ｜ 歐易生物 V22.5 48

44

2021 年 IF：7.34

單細(xì)胞事業(yè)部 ｜ 歐易生物 V22.5 49

45

2021 年 IF：9.261