3159 – A SINGLE-CELL PROTEIN-TRANSCRIPTOME ATLAS OF HAEMATOPOIESIS ACROSS THE HUMAN LIFESPAN
Experimental Hematology(2023)
Abstract
Throughout an individual's life, human haematopoiesis exhibits significant variations, likely as a response to evolving demands and physiological needs. Age-related changes in the blood system are also thought to impair its functionality. In this study, I introduce a multi-omic comprehensive atlas that combines single-cell surface protein detection and transcriptomic profiling for haematopoietic progenitor and mature cells across various stages of human development using CITE-seq. By taking advantage of a custom panel of 198 oligo conjugated antibodies, we successfully profiled over 250,000 cells collected from tissues representing different stages of human development, such as prenatal development (including yolk sac, embryonic and fetal liver, and bone marrow), newborn (cord blood), pediatric (bone marrow), as well as young and aged adult (bone marrow). I developed a bioinformatic pipeline to enable integrated analysis of samples from numerous individuals and tissues across the different developmental stages. Our latest unreported findings for differential abundance analysis indicate an initial lymphoid-skewed tendency emerging from FBM, intensifying during the pediatric phase, and gradually diminishing as one approaches adulthood. Preliminary data also reveal the presence of a distinct HSC population exclusive to the fetal stage. This extensive atlas serves as a valuable resource and reference, shedding light on the stage and tissue-specific characteristics of human haematopoiesis. Our analysis has revealed unique surface protein profiles and differentiation biases already present in the prenatal tissues (Jardine et al., Nature 2021). Throughout an individual's life, human haematopoiesis exhibits significant variations, likely as a response to evolving demands and physiological needs. Age-related changes in the blood system are also thought to impair its functionality. In this study, I introduce a multi-omic comprehensive atlas that combines single-cell surface protein detection and transcriptomic profiling for haematopoietic progenitor and mature cells across various stages of human development using CITE-seq. By taking advantage of a custom panel of 198 oligo conjugated antibodies, we successfully profiled over 250,000 cells collected from tissues representing different stages of human development, such as prenatal development (including yolk sac, embryonic and fetal liver, and bone marrow), newborn (cord blood), pediatric (bone marrow), as well as young and aged adult (bone marrow). I developed a bioinformatic pipeline to enable integrated analysis of samples from numerous individuals and tissues across the different developmental stages. Our latest unreported findings for differential abundance analysis indicate an initial lymphoid-skewed tendency emerging from FBM, intensifying during the pediatric phase, and gradually diminishing as one approaches adulthood. Preliminary data also reveal the presence of a distinct HSC population exclusive to the fetal stage. This extensive atlas serves as a valuable resource and reference, shedding light on the stage and tissue-specific characteristics of human haematopoiesis. Our analysis has revealed unique surface protein profiles and differentiation biases already present in the prenatal tissues (Jardine et al., Nature 2021).
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Key words
haematopoiesis,lifespan,single-cell,protein-transcriptome
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