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      Decoding human fetal liver haematopoiesis

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      Author(s): 1 , 1 , 1 , 1 , 1 , 1 , 2 , 3 , 1 , 3 , 1 , 1 , 1 , 5 , 3 , 3 , 3 , 4 , 1 , 1 , 1 , 1 , 1 , 18 , 1 , 1 , 6 , 3 , 1 , 3 , 3 , 7 , 8 , 1 , 1 , 1 , 7 , 3 , 10 , 10 , 10 , 10 , 10 , 10 , 12 , 10 , 10 , 1 , 11 , 9 , 13 , 10 , 14 , 5 , 15 , 2 , 2 , 16 , * , 2 , * , 3 , 17 , * , 1 , 3 , 18 , *
      Publication date (Electronic):
      Journal: Nature
      Keywords: human development, haematopoiesis, immunology, single cell RNA-sequencing, liver, skin, kidney, yolk-sac

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          Summary

          Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells/multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Using single cell transcriptome profiling of ~140,000 liver and ~74,000 skin, kidney and yolk sac cells, we identify the repertoire of human blood and immune cells during development. We infer differentiation trajectories from HSC/MPPs and evaluate the impact of tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, NK and ILC precursors in the yolk sac. We demonstrate a shift in fetal liver haematopoietic composition during gestation away from being erythroid-predominant, accompanied by a parallel change in HSC/MPP differentiation potential, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a valuable reference for harnessing the therapeutic potential of HSC/MPPs.

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          A single-cell molecular map of mouse gastrulation and early organogenesis

          Blanca Pijuan-Sala, Jonathan A. Griffiths, Carolina Guibentif … (2019)
          Across the animal kingdom, gastrulation represents a key developmental event during which embryonic pluripotent cells diversify into lineage-specific precursors that will generate the adult organism. Here we report the transcriptional profiles of 116,312 single cells from mouse embryos collected at nine sequential time-points ranging from 6.5 to 8.5 days post-fertilisation. We reconstruct a molecular map of cellular differentiation from pluripotency towards all major embryonic lineages, and explore the complex events involved in the convergence of visceral and primitive streak-derived endoderm. Furthermore, we demonstrate how combining temporal and transcriptional information illuminates gene function by single-cell profiling of Tal1 −/− chimeric embryos, with our analysis revealing defects in early mesoderm diversification. Taken together, this comprehensive delineation of mammalian cell differentiation trajectories in vivo represents a baseline for understanding the effects of gene mutations during development as well as a baseline for the optimisation of in vitro differentiation protocols for regenerative medicine.
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            Is Open Access

            AnimalTFDB 3.0: a comprehensive resource for annotation and prediction of animal transcription factors

            Hui Hu, Ya-Ru Miao, Long-Hao Jia … (2018)
            Abstract The Animal Transcription Factor DataBase (AnimalTFDB) is a resource aimed to provide the most comprehensive and accurate information for animal transcription factors (TFs) and cofactors. The AnimalTFDB has been maintained and updated for seven years and we will continue to improve it. Recently, we updated the AnimalTFDB to version 3.0 (http://bioinfo.life.hust.edu.cn/AnimalTFDB/) with more data and functions to improve it. AnimalTFDB contains 125,135 TF genes and 80,060 transcription cofactor genes from 97 animal genomes. Besides the expansion in data quantity, some new features and functions have been added. These new features are: (i) more accurate TF family assignment rules; (ii) classification of transcription cofactors; (iii) TF binding sites information; (iv) the GWAS phenotype related information of human TFs; (v) TF expressions in 22 animal species; (vi) a TF binding site prediction tool to identify potential binding TFs for nucleotide sequences; (vii) a separate human TF database web interface (HumanTFDB) was designed for better utilizing the human TFs. The new version of AnimalTFDB provides a comprehensive annotation and classification of TFs and cofactors, and will be a useful resource for studies of TF and transcription regulation.
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              Functionally Distinct Subsets of Lineage-Biased Multipotent Progenitors Control Blood Production in Normal and Regenerative Conditions.

              Eric Pietras, Damien Reynaud, Yoon-A Kang … (2015)
              Despite great advances in understanding the mechanisms underlying blood production, lineage specification at the level of multipotent progenitors (MPPs) remains poorly understood. Here, we show that MPP2 and MPP3 are distinct myeloid-biased MPP subsets that work together with lymphoid-primed MPP4 cells to control blood production. We find that all MPPs are produced in parallel by hematopoietic stem cells (HSCs), but with different kinetics and at variable levels depending on hematopoietic demands. We also show that the normally rare myeloid-biased MPPs are transiently overproduced by HSCs in regenerating conditions, hence supporting myeloid amplification to rebuild the hematopoietic system. This shift is accompanied by a reduction in self-renewal activity in regenerating HSCs and reprogramming of MPP4 fate toward the myeloid lineage. Our results support a dynamic model of blood development in which HSCs convey lineage specification through independent production of distinct lineage-biased MPP subsets that, in turn, support lineage expansion and differentiation.
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                Author and article information

                Journal
                Journal ID (nlm-journal-id): 0410462
                Journal ID (nlm-ta): Nature
                Journal ID (iso-abbrev): Nature
                Title: Nature
                ISSN (Print): 0028-0836
                ISSN (Electronic): 1476-4687
                Publication date Nihms-submitted: 10 September 2019
                Publication date (Electronic): 09 October 2019
                Publication date (Print): October 2019
                Publication date PMC-release: 09 April 2020
                Volume: 574
                Issue: 7778
                Pages: 365-371
                Affiliations
                [1 ]Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
                [2 ]Department of Haematology and Wellcome and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, CB2 2XY, UK
                [3 ]Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK
                [4 ]European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge, CB10 1SD UK
                [5 ]Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 Rue Moreau, F-75012 Paris, France
                [6 ]Department of Pathology, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne NE2 4LP, UK
                [7 ]Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK
                [8 ]School of Computing, Newcastle University, NE4 5TG, UK
                [9 ]Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA 02129, USA
                [10 ]Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA
                [11 ]Haematology Department, Royal Victoria Infirmary, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK
                [12 ]Data Sciences Platform, Broad Institute of Harvard and MIT, Cambridge, MA, USA
                [13 ]Department of Paediatrics, University of Oxford, Oxford OX3 9DS, UK
                [14 ]Howard Hughes Medical Institute, Koch Institute of Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
                [15 ]MRC Molecular Haematology Unit and Department of Paediatrics, Weatherall Institute of Molecular Medicine, University of Oxford, and BRC Blood Theme, NIHR Oxford Biomedical Centre, Oxford OX3 9DS, UK
                [16 ]Department of Paediatrics, University of Cambridge, Cambridge CB2 0SP, UK
                [17 ]Theory of Condensed Matter Group, Cavendish Laboratory/Department of Physics, University of Cambridge, Cambridge CB3 0HE, UK
                [18 ]Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne NE2 4LP, UK
                Author notes
                [* ]Corresponding authors
                Article
                Manuscript ID: EMS84343
                DOI: 10.1038/s41586-019-1652-y
                PMC ID: 6861135
                PubMed ID: 31597962
                SO-VID: 0808555f-7589-49d3-a5aa-e2b905b955cb
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                Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

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                Subject: Article

                ScienceOpen disciplines: Uncategorized
                Keywords: human development,haematopoiesis,immunology,single cell rna-sequencing,liver,skin,kidney,yolk-sac
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                ScienceOpen disciplines: Uncategorized
                Keywords: human development, haematopoiesis, immunology, single cell rna-sequencing, liver, skin, kidney, yolk-sac

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