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Single-cell transcriptomic landscape of human blood cells.

ABSTRACT: High throughput single-cell RNA-seq has been successfully implemented to dissect the cellular and molecular features underlying hematopoiesis. However, an elaborate and comprehensive transcriptome reference of the whole blood system is lacking. Here, we profiled the transcriptomes of 7551 human blood cells representing 32 immunophenotypic cell types, including hematopoietic stem cells, progenitors and mature blood cells derived from 21 healthy donors. With high sequencing depth and coverage, we constructed a single-cell transcriptional atlas of blood cells (ABC) on the basis of both protein-coding genes and long noncoding RNAs (lncRNAs), and showed a high consistence between them. Notably, putative lncRNAs and transcription factors regulating hematopoietic cell differentiation were identified. While common transcription factor regulatory networks were activated in neutrophils and monocytes, lymphoid cells dramatically changed their regulatory networks during differentiation. Furthermore, we showed a subset of nucleated erythrocytes actively expressing immune signals, suggesting the existence of erythroid precursors with immune functions. Finally, a web portal offering transcriptome browsing and blood cell type prediction has been established. Thus, our work provides a transcriptional map of human blood cells at single-cell resolution, thereby offering a comprehensive reference for the exploration of physiological and pathological hematopoiesis.

SUBMITTER: Xie X

PROVIDER: S-EPMC8288407 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Single-cell transcriptomic landscape of human blood cells.

Xie Xiaowei X Liu Mengyao M Zhang Yawen Y Wang Bingrui B Zhu Caiying C Wang Chenchen C Li Qing Q Huo Yingying Y Guo Jiaojiao J Xu Changlu C Hu Linping L Pang Aiming A Ma Shihui S Wang Lina L Cao Wenbin W Chen Shulian S Li Qiuling Q Zhang Sudong S Zhao Xueying X Zhou Wen W Luo Hongbo H Zheng Guoguang G Jiang Erlie E Feng Sizhou S Chen Lixiang L Shi Lihong L Cheng Hui H Hao Sha S Zhu Ping P Cheng Tao T

National science review 20200824 3

High throughput single-cell RNA-seq has been successfully implemented to dissect the cellular and molecular features underlying hematopoiesis. However, an elaborate and comprehensive transcriptome reference of the whole blood system is lacking. Here, we profiled the transcriptomes of 7551 human blood cells representing 32 immunophenotypic cell types, including hematopoietic stem cells, progenitors and mature blood cells derived from 21 healthy donors. With high sequencing depth and coverage, we ...[more]

PMID: 34691592

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Project description:Study questionWhat is the molecular landscape underlying the functional decline of human testicular ageing?Summary answerThe present study provides a comprehensive single-cell transcriptomic atlas of testes from young and old humans and offers insights into the molecular mechanisms and potential targets for human testicular ageing.What is known alreadyTesticular ageing is known to cause male age-related fertility decline and hypogonadism. Dysfunction of testicular cells has been considered as a key factor for testicular ageing.Study design, size, durationHuman testicular biopsies were collected from three young individuals and three old individuals to perform single-cell RNA sequencing (scRNA-seq). The key results were validated in a larger cohort containing human testicular samples from 10 young donors and 10 old donors.Participants/materials, setting, methodsscRNA-seq was used to identify gene expression signatures for human testicular cells during ageing. Ageing-associated changes of gene expression in spermatogonial stem cells (SSCs) and Leydig cells (LCs) were analysed by gene set enrichment analysis and validated by immunofluorescent and functional assays. Cell-cell communication analysis was performed using CellChat.Main results and the role of chanceThe single-cell transcriptomic landscape of testes from young and old men was surveyed, revealing age-related changes in germline and somatic niche cells. In-depth evaluation of the gene expression dynamics in germ cells revealed that the disruption of the base-excision repair pathway is a prominent characteristic of old SSCs, suggesting that defective DNA repair in SSCs may serve as a potential driver for increased de novo germline mutations with age. Further analysis of ageing-associated transcriptional changes demonstrated that stress-related changes and cytokine pathways accumulate in old somatic cells. Age-related impairment of redox homeostasis in old LCs was identified and pharmacological treatment with antioxidants alleviated this cellular dysfunction of LCs and promoted testosterone production. Lastly, our results revealed that decreased pleiotrophin signalling was a contributing factor for impaired spermatogenesis in testicular ageing.Large scale dataThe scRNA-seq sequencing and processed data reported in this paper were deposited at the Genome Sequence Archive (https://ngdc.cncb.ac.cn/), under the accession number HRA002349.Limitations, reasons for cautionOwing to the difficulty in collecting human testis tissue, the sample size was limited. Further in-depth functional and mechanistic studies are warranted in future.Wider implications of the findingsThese findings provide a comprehensive understanding of the cell type-specific mechanisms underlying human testicular ageing at a single-cell resolution, and suggest potential therapeutic targets that may be leveraged to address age-related male fertility decline and hypogonadism.Study funding/competing interest(s)This work was supported by the National Key Research and Development Program of China (2022YFA1104100), the National Natural Science Foundation of China (32130046, 82171564, 82101669, 82371611, 82371609, 82301796), the Natural Science Foundation of Guangdong Province, China (2022A1515010371), the Major Project of Medical Science and Technology Development Research Center of National Health Planning Commission, China (HDSL202001000), the Open Project of NHC Key Laboratory of Male Reproduction and Genetics (KF202001), the Guangdong Province Regional Joint Fund-Youth Fund Project (2021A1515110921, 2022A1515111201), and the China Postdoctoral Science Foundation (2021M703736). The authors declare no conflict of interest.

Project description:IntroductionAdvanced paternal age of reproduction is an increasing trend, especially in developed countries and areas. This trend results in elevated risks of adverse reproductive outcomes such as reduced fertility rates, increased pregnancy loss, and poor childhood health. Yet, a systematic profiling of aging-associated molecular and cellular alterations in testicular tissue is still missing.ObjectivesWe aimed to dissect aging-associated molecular characteristics in testes of mice.MethodsSingle-cell transcriptomic sequencing and analysis were conducted in testes of young (2 months old) and old mice (24 months old). Immunofluorescences and immunochemistry were used to characterize aging-associated phenotypes and verify single cell sequence results.ResultsHere, we constructed the first single-cell transcriptomic atlases of testes of young and old mice. In-depth dissection of aging-dependent transcriptional alterations in specific cell types revealed multiple dysregulated biological processes such as increased 'senescence-associated secretory phenotype' and 'inflammation', which were major aging-associated characteristics. Further analysis of aging-related differentially expressed genes uncovered a disrupted balance of undifferentiated and differentiated spermatogonia stem cells in spermatogonia, indicative of a potential role of spermatogonia stem cells in aging-associated subfertility. Importantly, for the first time, our results identified an increased subtype of aging-specific macrophages, which may contribute to a hostile proinflammatory microenvironment during testicular aging.ConclusionTaken together, our findings depict the distinct single-cell transcriptional features of the aged mouse testes and provide enormous resources for a comprehensive understanding of the cell-type-specific molecular mechanisms underlying mouse testicular aging, which may shed light on developing novel potential diagnostic biomarkers and therapeutic targets for age-associated male subfertility.

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Single-cell transcriptomic landscape of human blood cells.

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Single-cell transcriptomic landscape of human blood cells.

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