Combined Single-Cell Functional and Gene Expression Analysis Resolves Heterogeneity within Stem Cell Populations
Open accessAbstract
Heterogeneity within the self-renewal durability of adult hematopoietic stem cells (HSCs) challenges our understanding of the molecular framework underlying HSC function. Gene expression studies have been hampered by the presence of multiple HSC subtypes and contaminating non-HSCs in bulk HSC populations. To gain deeper insight into the gene expression program of murine HSCs, we combined single-cell functional assays with flow cytometric index sorting and single-cell gene expression assays. Through bioinformatic integration of these datasets, we designed an unbiased sorting strategy that separates non-HSCs away from HSCs, and single-cell transplantation experiments using the enriched population were combined with RNA-seq data to identify key molecules that associate with long-term durable self-renewal, producing a single-cell molecular dataset that is linked to functional stem cell activity. Finally, we demonstrated the broader applicability of this approach for linking key molecules with defined cellular functions in another stem cell system.
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A t-SNE variant that learns a mapping via a deep neural network is limited to massive data sets because of its large parameter space.
“A t-SNE variant that learns a mapping based on a deep neural network has been suggested111; while it is applicable only to massive data sets because of its large parameter space, as single-cell data grow it may increase in utility.”
From Revealing the vectors of cellular identity with single-cell genomics (2016) · cites this paper as [111]
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Cites
Breiman, L. (2001) · Machine Learning · doi:10.1023/a:1010933404324 · Cited by 133,538 · see citing works
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709 · see citing works
(2008) · Journal of Machine Learning Research · Cited by 33,051 · see citing works
HTSeq—a Python framework to work with high-throughput sequencing data
Anders, S., Pyl, P. T., & Huber, W. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btu638 · Cited by 21,464 · see citing works
Full-length RNA-seq from single cells using Smart-seq2
Picelli, S., Faridani, O. R., Björklund, Å. K., Winberg, G., Sagasser, S., & Sandberg, R. (2014) · Nature Protocols · doi:10.1038/nprot.2014.006 · Cited by 4,137 · see citing works
Kiel, M. J., Yilmaz, Ö. H., Iwashita, T., Yilmaz, O. H., Terhorst, C., & Morrison, S. J. (2005) · Cell · doi:10.1016/j.cell.2005.05.026 · Cited by 3,168 · see citing works
Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo.
Goodell, M. A., Brose, K., Paradis, G. A., Conner, A. N., & Mulligan, R. C. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.4.1797 · Cited by 2,902 · see citing works
A clonogenic common myeloid progenitor that gives rise to all myeloid lineages
Akashi, K., Traver, D., Miyamoto, T., & Weissman, I. L. (2000) · Nature · doi:10.1038/35004599 · Cited by 2,617 · see citing works
Wilson, A., Laurenti, E., Oser, G., van der Wath, R. C., Blanco-Bose, W., Jaworski, M., Offner, S., Dunant, C. F., Eshkind, L., Bockamp, E., et al. (2008) · Cell · doi:10.1016/j.cell.2008.10.048 · Cited by 1,908 · see citing works
Amir, E.-A. D., Davis, K. L., Tadmor, M. D., Simonds, E. F., Levine, J. H., Bendall, S. C., Shenfeld, D. K., Krishnaswamy, S., Nolan, G. P., & Pe'er, D. (2013) · Nature Biotechnology · doi:10.1038/nbt.2594 · Cited by 1,550 · see citing works
Identification of Flt3+ Lympho-Myeloid Stem Cells Lacking Erythro-Megakaryocytic Potential
Adolfsson, J., Månsson, R., Buza-Vidas, N., Hultquist, A., Liuba, K., Jensen, C. T., Bryder, D., Yang, L., Borge, O. J., Thorén, L., et al. (2005) · Cell · doi:10.1016/j.cell.2005.02.013 · Cited by 1,229 · see citing works
Buettner, F., Natarajan, K. N., Casale, F. P., Proserpio, V., Scialdone, A., Theis, F. J., Teichmann, S. A., Marioni, J. C., & Stegle, O. (2015) · Nature Biotechnology · doi:10.1038/nbt.3102 · Cited by 1,136 · see citing works
Self-citationDnmt3a is essential for hematopoietic stem cell differentiation
Challen, G. A., Sun, D., Jeong, M., Luo, M., Jelinek, J., Berg, J. S., Bock, C., Vasanthakumar, A., Gu, H., Xi, Y., et al. (2012) · Nature Genetics · doi:10.1038/ng.1009 · Cited by 1,122 · see citing works
Accounting for technical noise in single-cell RNA-seq experiments
Brennecke, P., Anders, S., Kim, J. K., Kołodziejczyk, A. A., Zhang, X., Proserpio, V., Baying, B., Benes, V., Teichmann, S. A., Marioni, J. C., et al. (2013) · Nature Methods · doi:10.1038/nmeth.2645 · Cited by 979 · see citing works
Guo, G., Huss, M., Tong, G. Q., Wang, C., Sun, L., Clarke, N. D., & Robson, P. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.02.012 · Cited by 806 · see citing works
Fundamental properties of unperturbed haematopoiesis from stem cells in vivo
Busch, K., Klapproth, K., Barile, M., Flossdorf, M., Holland-Letz, T., Schlenner, S. M., Reth, M., Höfer, T., & Rodewald, H.-R. (2015) · Nature · doi:10.1038/nature14242 · Cited by 769 · see citing works
Yamamoto, R., Morita, Y., Ooehara, J., Hamanaka, S., Onodera, M., Rudolph, K. L., Ema, H., & Nakauchi, H. (2013) · Cell · doi:10.1016/j.cell.2013.08.007 · Cited by 745 · see citing works
Bryder, D., Rossi, D. J., & Weissman, I. L. (2006) · American Journal Of Pathology · doi:10.2353/ajpath.2006.060312 · Cited by 733 · see citing works
Adolfsson, J., Borge, O. J., Bryder, D., Theilgaard‐Mönch, K., Åstrand‐Grundström, I., Sitnicka, E., Sasaki, Y., & Jacobsen, S. E. W. (2001) · Immunity · doi:10.1016/s1074-7613(01)00220-5 · Cited by 712 · see citing works
Beerman, I., Bhattacharya, D., Zandi, S., Sigvardsson, M., Weissman, I. L., Bryder, D., & Rossi, D. J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000834107 · Cited by 711 · see citing works
Platelet-biased stem cells reside at the apex of the haematopoietic stem-cell hierarchy
Sanjuán-Pla, A., Macaulay, I. C., Jensen, C. T., Woll, P. S., Luis, T. C., Mead, A. J., Moore, S., Carella, C., Matsuoka, S., Jones, T., et al. (2013) · Nature · doi:10.1038/nature12495 · Cited by 653 · see citing works
Self-citationLong-Term Propagation of Distinct Hematopoietic Differentiation Programs In Vivo
Dykstra, B. J., Kent, D. G., Bowie, M. B., McCaffrey, L., Hamilton, M. J., Lyons, K., Lee, S.-J., Brinkman, R. R., & Eaves, C. J. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.05.015 · Cited by 632 · see citing works
Self-citationDistinct Hematopoietic Stem Cell Subtypes Are Differentially Regulated by TGF-β1
Challen, G. A., Boles, N. C., Chambers, S. M., & Goodell, M. A. (2010) · Cell stem cell · doi:10.1016/j.stem.2010.02.002 · Cited by 580 · see citing works
Inflammatory modulation of HSCs: viewing the HSC as a foundation for the immune response
King, K. Y., & Goodell, M. A. (2011) · Nature reviews. Immunology · doi:10.1038/nri3062 · Cited by 565 · see citing works
Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment
Morita, Y., Ema, H., & Nakauchi, H. (2010) · The Journal of Experimental Medicine · doi:10.1084/jem.20091318 · Cited by 456 · see citing works
Diverse and heritable lineage imprinting of early haematopoietic progenitors
Naik, S. H., Perié, L., Swart, E., Gerlach, C., van Rooij, N., de Boer, R. J., & Schumacher, T. N. (2013) · Nature · doi:10.1038/nature12013 · Cited by 416 · see citing works
Hematopoietic Cytokines Can Instruct Lineage Choice
Rieger, M. A., Hoppe, P. S., Smejkal, B. M., Eitelhuber, A. C., & Schroeder, T. (2009) · Science · doi:10.1126/science.1171461 · Cited by 404 · see citing works
Månsson, R., Hultquist, A., Luc, S., Yang, L., Anderson, K., Kharazi, S., Al-Hashmi, S., Liuba, K., Thorén, L., Adolfsson, J., et al. (2007) · Immunity · doi:10.1016/j.immuni.2007.02.013 · Cited by 353 · see citing works
Kiel, M. J., Radice, G. L., & Morrison, S. J. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.06.001 · Cited by 343 · see citing works
The stem cell niche: theme and variations
Ohlstein, B., Kai, T., Decotto, E., & Spradling, A. C. (2004) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2004.09.003 · Cited by 341 · see citing works
Kent, D. G., Copley, M. R., Benz, C., Wöhrer, S., Dykstra, B. J., Ma, E., Cheyne, J., Zhao, Y., Bowie, M. B., Zhao, Y. S., et al. (2009) · Blood · doi:10.1182/blood-2008-12-192054 · Cited by 336 · see citing works
Self-citationPhenotypic and functional characterisation of the luminal cell hierarchy of the mammary gland
Shehata, M., Teschendorff, A., Sharp, G., Novcic, N., Russell, I. A., Avril, S., Prater, M., Eirew, P., Caldas, C., Watson, C. J., et al. (2012) · Breast Cancer Research · doi:10.1186/bcr3334 · Cited by 306 · see citing works
Self-citationHeterogeneity and hierarchy of hematopoietic stem cells
Ema, H., Morita, Y., & Suda, T. (2013) · Experimental Hematology · doi:10.1016/j.exphem.2013.11.004 · Cited by 150 · see citing works
Roles of Sca-1 in hematopoietic stem/progenitor cell function
Bradfute, S. B., Graubert, T. A., & Goodell, M. A. (2005) · Experimental Hematology · doi:10.1016/j.exphem.2005.04.001 · Cited by 125 · see citing works
Weksberg, D. C., Chambers, S. M., Boles, N. C., & Goodell, M. A. (2007) · Blood · doi:10.1182/blood-2007-09-115006 · Cited by 123 · see citing works
Moignard, V., Macaulay, I., Swiers, G., Buettner, F., Schütte, J., Calero-Nieto, F., Kinston, S., Joshi, A., Hannah, R., Theis, F. J., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2709 · Cited by 116 · see citing works
Self-citationDevelopmental changes in hematopoietic stem cell properties
Copley, M. R., & Eaves, C. J. (2013) · Experimental & Molecular Medicine · doi:10.1038/emm.2013.98 · Cited by 91 · see citing works
Kent, D. G., Li, J., Tanna, H., Fink, J., Kirschner, K., Pask, D. C., Silber, Y., Hamilton, T. L., Sneade, R., Simons, B. D., et al. (2013) · PLoS Biology · doi:10.1371/journal.pbio.1001576 · Cited by 85 · see citing works
Self-citationGrinenko, T., Arndt, K., Portz, M., Mende, N., Günther, M., Cosgun, K. N., Alexopoulou, D., Lakshmanaperumal, N., Henry, I., Dahl, A., et al. (2014) · The Journal of Experimental Medicine · doi:10.1084/jem.20131115 · Cited by 84 · see citing works
Kent, D. G., Dykstra, B. J., Cheyne, J., Ma, E., & Eaves, C. J. (2008) · Blood · doi:10.1182/blood-2007-10-117820 · Cited by 63 · see citing works
Self-citationTranscriptional Regulation of Haematopoietic Stem Cells
Wilkinson, A. C., & Göttgens, B. (2013) · Advances in experimental medicine and biology · doi:10.1007/978-94-007-6621-1_11 · Cited by 58 · see citing works
Self-citationRecent Advances in Flow Cytometric Cell Sorting
Osborne, G. W. (2011) · Methods in cell biology · doi:10.1016/b978-0-12-374912-3.00021-3 · Cited by 36 · see citing works
Eirew, P. D., Stingl, J., & Eaves, C. J. (2010) · Nature Protocols · doi:10.1038/nprot.2010.148 · Cited by 36 · see citing works
Self-citationPrick, J. C. M., de Haan, G., Green, A. R., & Kent, D. G. (2014) · Experimental Hematology · doi:10.1016/j.exphem.2014.07.268 · Cited by 20 · see citing works
Self-citation
Flagged first, then by citations
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Sorted by citations
Simultaneous epitope and transcriptome measurement in single cells
Stoeckius, M., Hafemeister, C., Stephenson, W., Houck-Loomis, B., Chattopadhyay, P. K., Swerdlow, H., Satija, R., & Smibert, P. (2017) · Nature Methods · doi:10.1038/nmeth.4380 · Cited by 3,098 · see citing works
A step-by-step workflow for low-level analysis of single-cell RNA-seq data with Bioconductor
Lun, A. T. L., McCarthy, D. J., & Marioni, J. C. (2016) · F1000Research · doi:10.12688/f1000research.9501.2 · Cited by 1,586 · see citing works
Integrative single-cell analysis
Stuart, T., & Satija, R. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0093-7 · Cited by 1,460 · see citing works
BCG Educates Hematopoietic Stem Cells to Generate Protective Innate Immunity against Tuberculosis
Kaufmann, E., Sanz, J., Dunn, J. L., Khan, N., Mendonça, L. E., Pacis, A., Tzelepis, F., Pernet, E., Dumaine, A., Grenier, J.-C., et al. (2018) · Cell · doi:10.1016/j.cell.2017.12.031 · Cited by 1,191 · see citing works
Human haematopoietic stem cell lineage commitment is a continuous process
Velten, L., Haas, S. F., Raffel, S., Blaszkiewicz, S., Islam, S., Hennig, B. P., Hirche, C., Lutz, C., Buss, E. C., Nowak, D., et al. (2017) · Nature Cell Biology · doi:10.1038/ncb3493 · Cited by 925 · see citing works
Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
Cossarizza, A., Chang, H., Radbruch, A., Acs, A., Adam, D., Adam‐Klages, S., Agace, W. W., Aghaeepour, N., Akdiş, M., Allez, M., et al. (2019) · European Journal of Immunology · doi:10.1002/eji.201970107 · Cited by 982 · see citing works
From haematopoietic stem cells to complex differentiation landscapes
Laurenti, E., & Göttgens, B. (2018) · Nature · doi:10.1038/nature25022 · Cited by 830 · see citing works
Self-citationA step-by-step workflow for low-level analysis of single-cell RNA-seq data
Lun, A. T. L., McCarthy, D. J., & Marioni, J. C. (2016) · F1000Research · doi:10.12688/f1000research.9501.1 · Cited by 1,511 · see citing works
A single-cell resolution map of mouse hematopoietic stem and progenitor cell differentiation
Nestorowa, S., Hamey, F. K., Pijuan Sala, B., Diamanti, E., Shepherd, M., Laurenti, E., Wilson, N. K., Kent, D. G., & Göttgens, B. (2016) · Blood · doi:10.1182/blood-2016-05-716480 · Cited by 768 · see citing works
Self-citationDe Novo Prediction of Stem Cell Identity using Single-Cell Transcriptome Data
Grün, D., Muraro, M. J., Boisset, J.-C., Wiebrands, K., Lyubimova, A., Dharmadhikari, G., van den Born, M., van Es, J., Jansen, E., Clevers, H., et al. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.05.010 · Cited by 586 · see citing works
Revealing the vectors of cellular identity with single-cell genomics
Wagner, A., Regev, A., & Yosef, N. (2016) · Nature Biotechnology · doi:10.1038/nbt.3711 · Cited by 632 · see citing works
Missing data and technical variability in single-cell RNA-sequencing experiments
Hicks, S. C., Townes, F. W., Teng, M., & Irizarry, R. A. (2018) · Biostatistics · doi:10.1093/biostatistics/kxx053 · Cited by 635 · see citing works
Power analysis of single-cell RNA-sequencing experiments
Svensson, V., Natarajan, K. N., Ly, L.-H., Miragaia, R. J., Labalette, C., Macaulay, I. C., Cvejic, A., & Teichmann, S. A. (2017) · Nature Methods · doi:10.1038/nmeth.4220 · Cited by 568 · see citing works
Self-citationSingle-cell transcriptomics to explore the immune system in health and disease
Stubbington, M. J. T., Rozenblatt–Rosen, O., Regev, A., & Teichmann, S. A. (2017) · Science · doi:10.1126/science.aan6828 · Cited by 560 · see citing works
Aging of hematopoietic stem cells
de Haan, G., & Lazare, S. S. (2018) · Blood · doi:10.1182/blood-2017-06-746412 · Cited by 432 · see citing works
Vitamin A-Retinoic Acid Signaling Regulates Hematopoietic Stem Cell Dormancy
Cabezas-Wallscheid, N., Buettner, F., Sommerkamp, P., Klimmeck, D., Ladel, L., Thalheimer, F. B., Pastor-Flores, D., Roma, L. P., Renders, S., Zeisberger, P., et al. (2017) · Cell · doi:10.1016/j.cell.2017.04.018 · Cited by 454 · see citing works
Self-citationGiustacchini, A., Thongjuea, S., Barkas, N., Woll, P. S., Povinelli, B. J., Booth, C. A. G., Sopp, P., Norfo, R., Rodriguez-Meira, A., Ashley, N., et al. (2017) · Nature Medicine · doi:10.1038/nm.4336 · Cited by 403 · see citing works
Hierarchically related lineage-restricted fates of multipotent haematopoietic stem cells
Carrelha, J., Meng, Y., Kettyle, L. M., Luis, T. C., Norfo, R., Alcolea, V., Boukarabila, H., Grasso, F., Gambardella, A. R., Grover, A., et al. (2018) · Nature · doi:10.1038/nature25455 · Cited by 385 · see citing works
Hematopoietic Stem Cells Are the Major Source of Multilineage Hematopoiesis in Adult Animals
Sawai, C. M., Babovic, S., Upadhaya, S., Knapp, D. J. H. F., Lavin, Y., Lau, C. M., Goloborodko, A., Feng, J., Fujisaki, J., Ding, L., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.08.007 · Cited by 381 · see citing works
Single‐cell analysis reveals cancer stem cell heterogeneity in hepatocellular carcinoma
Zheng, H., Pomyen, Y., Hernandez, M. O., Li, C., Livák, F., Tang, W., Dang, H. T., Greten, T. F., Davis, J. L., Zhao, Y., et al. (2018) · Hepatology · doi:10.1002/hep.29778 · Cited by 350 · see citing works
Detection and removal of barcode swapping in single-cell RNA-seq data
Griffiths, J. A., Richard, A. C., Bach, K., Lun, A. T. L., & Marioni, J. C. (2018) · Nature Communications · doi:10.1038/s41467-018-05083-x · Cited by 324 · see citing works
Bowling, S., Sritharan, D., Osorio, F. G., Nguyen, M., Cheung, P., Rodriguez-Fraticelli, A., Patel, S. H., Yuan, W.-C., Fujiwara, Y., Li, B. E., et al. (2020) · Cell · doi:10.1016/j.cell.2020.04.048 · Cited by 337 · see citing works
Challenges and emerging directions in single-cell analysis
Yuan, G., Cai, L., Elowitz, M. B., Enver, T., Fan, G., Guo, G., Irizarry, R. A., Kharchenko, P. V., Kim, J., Orkin, S. H., et al. (2017) · Genome biology · doi:10.1186/s13059-017-1218-y · Cited by 339 · see citing works
Highly multiplexed simultaneous detection of RNAs and proteins in single cells
Frei, A. P., Bava, F.-A., Zunder, E. R., Hsieh, E. W. Y., Chen, S.-Y., Nolan, G. P., & Gherardini, P. F. (2016) · Nature Methods · doi:10.1038/nmeth.3742 · Cited by 330 · see citing works
The chronic myeloid leukemia stem cell: stemming the tide of persistence
Holyoake, T. L., & Vetrie, D. L. P. (2017) · Blood · doi:10.1182/blood-2016-09-696013 · Cited by 312 · see citing works
GiniClust: detecting rare cell types from single-cell gene expression data with Gini index
Jiang, L., Chen, H., Pinello, L., & Yuan, G. (2016) · Genome biology · doi:10.1186/s13059-016-1010-4 · Cited by 296 · see citing works
M3Drop: dropout-based feature selection for scRNASeq
Andrews, T. S., & Hemberg, M. (2018) · Bioinformatics · doi:10.1093/bioinformatics/bty1044 · Cited by 283 · see citing works
Advanced Applications of RNA Sequencing and Challenges
Han, Y., Gao, S., Muegge, K., Zhang, W., & Zhou, B. (2015) · Bioinformatics and Biology Insights · doi:10.4137/bbi.s28991 · Cited by 277 · see citing works
New paradigms on hematopoietic stem cell differentiation
Cheng, H., Zheng, Z., & Cheng, T. (2019) · Protein & Cell · doi:10.1007/s13238-019-0633-0 · Cited by 275 · see citing works
Single-cell lineage tracing unveils a role for TCF15 in haematopoiesis
Rodriguez-Fraticelli, A., Weinreb, C., Wang, S., Migueles, R. P., Jankovic, M., Usart, M., Klein, A. M., Lowell, S., & Camargo, F. D. (2020) · Nature · doi:10.1038/s41586-020-2503-6 · Cited by 255 · see citing works
Single-cell analysis reveals the continuum of human lympho-myeloid progenitor cells
Karamitros, D., Stoilova, B., Aboukhalil, Z., Hamey, F., Reinisch, A., Samitsch, M., Quek, L. S., Otto, G., Repapi, E., Doondeea, J. B., et al. (2017) · Nature Immunology · doi:10.1038/s41590-017-0001-2 · Cited by 247 · see citing works
Self-citationEpithelial-Mesenchymal Micro-niches Govern Stem Cell Lineage Choices
Yang, H., Adam, R. C., Ge, Y., Hua, Z. L., & Fuchs, E. V. (2017) · Cell · doi:10.1016/j.cell.2017.03.038 · Cited by 249 · see citing works
A single-cell hematopoietic landscape resolves 8 lineage trajectories and defects in Kit mutant mice
Dahlin, J. S., Hamey, F. K., Pijuan-Sala, B., Shepherd, M., Lau, W. W. Y., Nestorowa, S., Weinreb, C., Wolock, S., Hannah, R., Diamanti, E., et al. (2018) · Blood · doi:10.1182/blood-2017-12-821413 · Cited by 233 · see citing works
Self-citationThe Human Cell Atlas bone marrow single-cell interactive web portal
Hay, S. B., Ferchen, K., Chetal, K., Grimes, H. L., & Salomonis, N. (2018) · Experimental Hematology · doi:10.1016/j.exphem.2018.09.004 · Cited by 256 · see citing works
Identifying cell populations with scRNASeq
Andrews, T. S., & Hemberg, M. (2017) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2017.07.002 · Cited by 240 · see citing works
DNA methylation disruption reshapes the hematopoietic differentiation landscape
Izzo, F., Lee, S. C., Poran, A., Chaligne, R., Gaiti, F., Gross, B., Murali, R. R., Deochand, S. D., Ang, C., Jones, P. W., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-0595-4 · Cited by 236 · see citing works
Peng, G., Suo, S., Chen, J., Chen, W., Liu, C. X., Fang, Y., Wang, R., Chen, S., Sun, N., Cui, G., et al. (2016) · Developmental Cell · doi:10.1016/j.devcel.2016.02.020 · Cited by 235 · see citing works
Epigenetic Memory Underlies Cell-Autonomous Heterogeneous Behavior of Hematopoietic Stem Cells
Yu, V. W. C., Yusuf, R. Z., Oki, T., Wu, J. W., Sáez, B., Wang, X., Cook, C., Baryawno, N., Ziller, M. J., Lee, E., et al. (2017) · Cell · doi:10.1016/j.cell.2017.02.010 · Cited by 233 · see citing works
Haematopoietic stem cell self-renewal in vivo and ex vivo
Wilkinson, A. C., Igarashi, K. J., & Nakauchi, H. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-020-0241-0 · Cited by 226 · see citing works
Myeloid progenitor cluster formation drives emergency and leukaemic myelopoiesis
Hérault, A., Binnewies, M., Leong, S., Calero‐Nieto, F. J., Zhang, S. Y., Kang, Y.-A., Wang, X., Pietras, E. M., Chu, S. H., Barry-Holson, K. Q., et al. (2017) · Nature · doi:10.1038/nature21693 · Cited by 207 · see citing works
Self-citationLarge-Scale Clonal Analysis Resolves Aging of the Mouse Hematopoietic Stem Cell Compartment
Yamamoto, R., Wilkinson, A. C., Ooehara, J., Lan, X., Lai, C.-Y., Nakauchi, Y., Pritchard, J. K., & Nakauchi, H. (2018) · Cell Stem Cell · doi:10.1016/j.stem.2018.03.013 · Cited by 202 · see citing works
Dou, M., Clair, G., Tsai, C., Xu, K., Chrisler, W., Sontag, R. L., Zhao, R., Moore, R. J., Liu, T., Paša‐Tolić, L., et al. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.9b03349 · Cited by 201 · see citing works
Epigenetic Memory Underlies Cell-Autonomous Heterogeneous Behavior of Hematopoietic Stem Cells
Yu, V. W. C., Yusuf, R. Z., Oki, T., Wu, J. W., Sáez, B., Wang, X., Cook, C., Baryawno, N., Ziller, M. J., Lee, E., et al. (2016) · Cell · doi:10.1016/j.cell.2016.10.045 · Cited by 197 · see citing works
Pal, B., Chen, Y., Vaillant, F., Jamieson, P. R., Gordon, L., Rios, A. C., Wilcox, S., Fu, N. Y., Liu, K. H., Jackling, F. C., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01560-x · Cited by 189 · see citing works
scIGANs: single-cell RNA-seq imputation using generative adversarial networks
Xu, Y., Zhang, Z., You, L., Liu, J., Fan, Z., & Zhou, X. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa506 · Cited by 182 · see citing works
Regulation of Hematopoiesis and Osteogenesis by Blood Vessel–Derived Signals
Ramasamy, S. K., Kusumbe, A. P., Itkin, T., Gur‐Cohen, S., Lapidot, T., & Adams, R. H. (2016) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-111315-124936 · Cited by 169 · see citing works
Hematopoietic Hierarchy – An Updated Roadmap
Zhang, Y., Gao, S., Xia, J., & Liu, F. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.06.001 · Cited by 167 · see citing works
Single-cell RNA-sequencing uncovers transcriptional states and fate decisions in haematopoiesis
Athanasiadis, E. I., Botthof, J. G., Andrés-Terré, H., Ferreira, L., Lió, P., & Cvejic, A. (2017) · Nature Communications · doi:10.1038/s41467-017-02305-6 · Cited by 163 · see citing works
Cell size is a determinant of stem cell potential during aging
Lengefeld, J., Cheng, C., Maretich, P., Blair, M., Hagen, H. R., McReynolds, M. R., Sullivan, E. J., Majors, K., Roberts, C., Kang, J. H., et al. (2021) · Science Advances · doi:10.1126/sciadv.abk0271 · Cited by 160 · see citing works
Psaila, B., Barkas, N., Iskander, D., Roy, A., Anderson, S. M., Ashley, N., Caputo, V. S., Lichtenberg, J., Loaiza, S., Bodine, D. M., et al. (2016) · Genome biology · doi:10.1186/s13059-016-0939-7 · Cited by 155 · see citing works
Haematopoietic stem cells: past, present and future
Ng, A. P., & Alexander, W. S. (2017) · Cell Death Discovery · doi:10.1038/cddiscovery.2017.2 · Cited by 154 · see citing works
Sanchez-Castillo, M., Blanco, D., Tienda-Luna, I. M., Carrion, M. C., & Huang, Y. (2018) · Bioinformatics · doi:10.1093/bioinformatics/btx605 · Cited by 151 · see citing works
Self-citationHematopoietic stem/progenitor cell commitment to the megakaryocyte lineage
Woolthuis, C. M., & Park, C. Y. (2016) · Blood · doi:10.1182/blood-2015-07-607945 · Cited by 138 · see citing works
Gur‐Cohen, S., Itkin, T., Chakrabarty, S., Graf, C., Kollet, Ó., Ludin, A., Golan, K., Kalinkovich, A., Ledergor, G., Wong, E., et al. (2015) · Nature Medicine · doi:10.1038/nm.3960 · Cited by 142 · see citing works
Long-term ex vivo expansion of mouse hematopoietic stem cells
Wilkinson, A. C., Ishida, R., Nakauchi, H., & Yamazaki, S. (2020) · Nature Protocols · doi:10.1038/s41596-019-0263-2 · Cited by 125 · see citing works
Single-cell transcriptional analysis reveals ILC-like cells in zebrafish
Hernández, P. P., Strzelecka, P. M., Athanasiadis, E. I., Hall, D., Robalo, A. F., Collins, C., Boudinot, P., Levraud, J., & Cvejic, A. (2018) · Science Immunology · doi:10.1126/sciimmunol.aau5265 · Cited by 130 · see citing works
Macrophages and Cardiovascular Health
Frodermann, V., & Nahrendorf, M. (2018) · Physiological Reviews · doi:10.1152/physrev.00068.2017 · Cited by 126 · see citing works
Single-cell epigenomic variability reveals functional cancer heterogeneity
Litzenburger, U. M., Buenrostro, J. D., Wu, B., Shen, Y., Sheffield, N. C., Kathiria, A., Greenleaf, W. J., & Chang, H. Y. (2017) · Genome Biology · doi:10.1186/s13059-016-1133-7 · Cited by 115 · see citing works
Nguyen, Q. H., Lukowski, S. W., Chiu, H. S., Senabouth, A., Bruxner, T. J. C., Christ, A. N., Palpant, N. J., & Powell, J. E. (2018) · Genome Research · doi:10.1101/gr.223925.117 · Cited by 118 · see citing works
Single Cell RNA Sequencing of Rare Immune Cell Populations
Nguyen, A., Khoo, W. H., Moran, I., Croucher, P. I., & Phan, T. G. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01553 · Cited by 120 · see citing works
Single-cell genomics: coming of age
Linnarsson, S., & Teichmann, S. A. (2016) · Genome biology · doi:10.1186/s13059-016-0960-x · Cited by 118 · see citing works
Zhou, H.-Y., Wang, F., & Tao, P. (2018) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.8b00652 · Cited by 119 · see citing works
Dignum, T., Varnum‐Finney, B., Srivatsan, S. R., Dozono, S., Waltner, O. G., Heck, A. M., Ishida, T., Nourigat-Mckay, C., Jackson, D. L., Rafii, S., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109675 · Cited by 112 · see citing works
Droplet-based single cell RNAseq tools: a practical guide
Salomon, R., Kaczorowski, D., Valdes-Mora, F., Nordon, R. E., Neild, A., Farbehi, N., Bartonicek, N., & Gallego-Ortega, D. (2019) · Lab on a Chip · doi:10.1039/c8lc01239c · Cited by 109 · see citing works
The hematopoietic stem-cell niche in health and leukemia
Sánchez‐Aguilera, A., & Méndez‐Ferrer, S. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2306-y · Cited by 105 · see citing works
Reconstructing blood stem cell regulatory network models from single-cell molecular profiles
Hamey, F., Nestorowa, S., Kinston, S., Kent, D. G., Wilson, N. K., & Göttgens, B. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1610609114 · Cited by 102 · see citing works
Self-citationStudying hematopoiesis using single-cell technologies
Ye, F., Huang, W., & Guo, G. (2017) · Journal of Hematology & Oncology · doi:10.1186/s13045-017-0401-7 · Cited by 100 · see citing works
Schönberger, K., Obier, N., Romero-Mulero, M. C., Cauchy, P., Mess, J., Pavlovich, P. V., Zhang, Y. W., Mitterer, M., Rettkowski, J., Lalioti, M., et al. (2021) · Cell stem cell · doi:10.1016/j.stem.2021.10.002 · Cited by 94 · see citing works
Gu, W., Nowak, W. N., Xie, Y., Bras, A. L., Hu, Y., Deng, J., Bhaloo, S. I., Lu, Y., Yuan, H., Fidanis, E., et al. (2019) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.119.312732 · Cited by 95 · see citing works
Haemopedia: An Expression Atlas of Murine Hematopoietic Cells
de Graaf, C. A., Choi, J., Baldwin, T. M., Bolden, J. E., Fairfax, K. A., Robinson, A. J., Biben, C., Morgan, C., Ramsay, K. A., Ng, A. P., et al. (2016) · Stem Cell Reports · doi:10.1016/j.stemcr.2016.07.007 · Cited by 89 · see citing works
Hui, T., Cao, Q., Wegrzyn-Woltosz, J., O’Neill, K., Hammond, C. A., Knapp, D. J. H. F., Laks, E., Moksa, M., Aparicio, S. A. J. R., Eaves, C. J., et al. (2018) · Stem Cell Reports · doi:10.1016/j.stemcr.2018.07.003 · Cited by 94 · see citing works
BTR: training asynchronous Boolean models using single-cell expression data
Lim, C. Y., Wang, H., Woodhouse, S., Piterman, N., Wernisch, L., Fisher, J., & Göttgens, B. (2016) · BMC Bioinformatics · doi:10.1186/s12859-016-1235-y · Cited by 81 · see citing works
Self-citationGrinenko, T., Eugster, A., Thielecke, L., Ramasz, B., Krüger, A., Dietz, S., Glauche, I., Gerbaulet, A., Bonin, M. V., Başak, O., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04188-7 · Cited by 87 · see citing works
Harnessing Hematopoietic Stem Cell Low Intracellular Calcium Improves Their Maintenance In Vitro
Luchsinger, L. L., Strikoudis, A., Danzl, N. M., Bush, E. C., Finlayson, M. O., Satwani, P., Sykes, M., Yazawa, M., & Snoeck, H. (2019) · Cell stem cell · doi:10.1016/j.stem.2019.05.002 · Cited by 88 · see citing works
Quantitative proteomics reveals specific metabolic features of acute myeloid leukemia stem cells
Raffel, S., Klimmeck, D., Falcone, M., Demir, A., Pouya, A., Zeisberger, P., Lutz, C., Tinelli, M., Bischel, O. E., Bullinger, L., et al. (2020) · Blood · doi:10.1182/blood.2019003654 · Cited by 88 · see citing works
Cosgrove, J., Hustin, L., de Boer, R. J., & Perié, L. (2021) · Trends in Immunology · doi:10.1016/j.it.2021.10.006 · Cited by 88 · see citing works
Niche derived netrin-1 regulates hematopoietic stem cell dormancy via its receptor neogenin-1
Renders, S., Svendsen, A. F., Panten, J., Rama, N., Maryanovich, M., Sommerkamp, P., Ladel, L., Redavid, A. R., Gibert, B., Lazare, S., et al. (2021) · Nature Communications · doi:10.1038/s41467-020-20801-0 · Cited by 83 · see citing works
Deciphering the metabolic heterogeneity of hematopoietic stem cells with single-cell resolution
Cao, J., Yao, Q. J., Wu, J., Chen, X., Huang, L., Liu, W., Qian, K., Wan, J., & Zhou, B. O. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2023.12.005 · Cited by 87 · see citing works
Shin, J. J., Schröder, M., Caiado, F., Wyman, S. K., Bray, N., Bordi, M., DeWitt, M. A., Vu, J. T., Kim, W., Hockemeyer, D. F., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108093 · Cited by 84 · see citing works
Woo, J. J., Clair, G., Williams, S., Feng, S., Tsai, C., Moore, R. J., Chrisler, W., Smith, R. D., Kelly, R., Paša‐Tolić, L., et al. (2022) · Cell Systems · doi:10.1016/j.cels.2022.02.003 · Cited by 83 · see citing works
Epigenetic Regulators as the Gatekeepers of Hematopoiesis
Rodrigues, C. P., Shvedunova, M., & Akhtar, A. (2020) · Trends in Genetics · doi:10.1016/j.tig.2020.09.015 · Cited by 85 · see citing works
Sommerkamp, P., Romero-Mulero, M. C., Narr, A., Ladel, L., Hustin, L., Schönberger, K., Renders, S., Altamura, S., Zeisberger, P., Jäcklein, K., et al. (2021) · Blood · doi:10.1182/blood.2020007876 · Cited by 83 · see citing works
Heterogeneity of Cancer Stem Cells: Rationale for Targeting the Stem Cell Niche
Boesch, M., Sopper, S., Zeimet, A. G., Reimer, D., Gastl, G. A., Ludewig, B., & Wolf, D. G. F. (2016) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2016.10.003 · Cited by 80 · see citing works
New insights into hematopoietic differentiation landscapes from single-cell RNA sequencing
Watcham, S., Kuciński, I., & Göttgens, B. (2019) · Blood · doi:10.1182/blood-2018-08-835355 · Cited by 77 · see citing works
Self-citationSpatial Genome Re-organization between Fetal and Adult Hematopoietic Stem Cells
Chen, C.-Y., Yu, W.-B., Tober, J., Gao, P., He, B., Lee, K., Trieu, T., Blobel, G., Speck, N., & Tan, K. (2019) · bioRxiv · doi:10.1016/j.celrep.2019.11.065 · Cited by 65 · see citing works
Molecular and cellular mechanisms of aging in hematopoietic stem cells and their niches
Zhang, L., Mack, R. M., Breslin, P., & Zhang, J. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00994-z · Cited by 78 · see citing works
Single‐cell technologies are revolutionizing the approach to rare cells
Proserpio, V., & Lönnberg, T. (2015) · Immunology and Cell Biology · doi:10.1038/icb.2015.106 · Cited by 76 · see citing works
Multi-site Neurogenin3 Phosphorylation Controls Pancreatic Endocrine Differentiation
Azzarelli, R., Hurley, C., Sznurkowska, M. K., Rulands, S., Hardwick, L. J. A., Gamper, I., Ali, F. R., McCracken, L., Hindley, C. J., McDuff, F. K. E., et al. (2017) · Developmental Cell · doi:10.1016/j.devcel.2017.04.004 · Cited by 78 · see citing works
Self-citationVariation is function: Are single cell differences functionally important?
Dueck, H., Eberwine, J. H., & Kim, J. (2015) · BioEssays · doi:10.1002/bies.201500124 · Cited by 76 · see citing works
Single-cell transcriptional analysis of normal, aberrant, and malignant hematopoiesis in zebrafish
Moore, F. E., Garcia, E. G., Lobbardi, R., Jain, E., Tang, Q., Moore, J. C., Cortes, M., Molodtsov, A. K., Kasheta, M., Luo, C. C., et al. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20152013 · Cited by 76 · see citing works
Mammalian Transcription Factor Networks: Recent Advances in Interrogating Biological Complexity
Wilkinson, A. C., Nakauchi, H., & Göttgens, B. (2017) · Cell Systems · doi:10.1016/j.cels.2017.07.004 · Cited by 76 · see citing works
Self-citationDefining Cell Identity with Single‐Cell Omics
Mincarelli, L., Lister, A., Lipscombe, J., & Macaulay, I. C. (2018) · PROTEOMICS · doi:10.1002/pmic.201700312 · Cited by 75 · see citing works
Self-citationApplication of single-cell genomics in cancer: promise and challenges
Wills, Q. F., & Mead, A. J. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv235 · Cited by 75 · see citing works
Optimal transport for single-cell and spatial omics
Bunne, C., Schiebinger, G., Krause, A., Regev, A., & Cuturi, M. (2024) · Nature Reviews Methods Primers · doi:10.1038/s43586-024-00334-2 · Cited by 71 · see citing works
Transcriptional control of dendritic cell development and functions
Amon, L., Lehmann, C. H. K., Barańska, A., Schoen, J., Heger, L., & Dudziak, D. (2019) · International review of cytology · doi:10.1016/bs.ircmb.2019.10.001 · Cited by 71 · see citing works
Impact of Mesenchymal Stem Cell Senescence on Inflammaging
Lee, B.-C., & Yu, K. (2020) · BMB Reports · doi:10.5483/bmbrep.2020.53.2.291 · Cited by 70 · see citing works
Sachs, K., Sarver, A. L., Noble-Orcutt, K. E., LaRue, R. S., Antony, M. L., Chang, D., Lee, Y., Navis, C. M., Hillesheim, A. L., Nykaza, I. R., et al. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-2932 · Cited by 67 · see citing works
Hematopoietic Stem Cell Factors: Their Functional Role in Self-Renewal and Clinical Aspects
Mann, Z., Sengar, M., Verma, Y. K., Rajalingam, R., & Raghav, P. K. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.664261 · Cited by 69 · see citing works
GATA2 Promotes Hematopoietic Development and Represses Cardiac Differentiation of Human Mesoderm
Castaño, J., Aranda, S., Bueno, C., Calero‐Nieto, F. J., Mejía-Ramírez, E., Mosquera, J. L., Blanco, E., Wang, X., Prieto, C., Zabaleta, L., et al. (2019) · Stem Cell Reports · doi:10.1016/j.stemcr.2019.07.009 · Cited by 66 · see citing works
Self-citationFate mapping of hematopoietic stem cells reveals two pathways of native thrombopoiesis
Morcos, M. N. F., Li, C., Munz, C. M., Greco, A., Dressel, N., Reinhardt, S., Sameith, K., Dahl, A., Becker, N. B., Roers, A., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-31914-z · Cited by 65 · see citing works
- Authors
- Wilson, N. K., Kent, D. G., Buettner, F., Shehata, M., Macaulay, I. C., Calero-Nieto, F. J., Sánchez Castillo, M., Oedekoven, C. A., Diamanti, E., Schulte, R., Ponting, C. P., Voet, T., Caldas, C., Stingl, J., Green, A. R., Theis, F. J., & Göttgens, B.
- Affiliations
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- Helmholtz Munich (DE)
- University of Cambridge (GB)
- Wellcome Sanger Institute (GB)
- Corresponding author
- Göttgens, Berthold
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2015-06
- Volume
- 16
- Issue
- 6
- Pages
- 712-724
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC4460190
- OpenAlex
- W1563425389
- Cited by
- 466
- References
- 44
- Citations by year
- 2026: 19 · 2025: 35 · 2024: 34 · 2023: 32 · 2022: 34 · 2021: 38 · 2020: 52 · 2019: 48 · 2018: 59 · 2017: 50 · 2016: 49 · 2015: 14 · 2014: 1
- FWCI
- 44.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Cell stem cell (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Lirias (submittedVersion, cc-by)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Site cant be reached (submittedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Funders
- Wellcome Trust (97922)
- Cancer Research UK (A17197, C14303, C14303 / A17197, 12765, 16942)
- National Institute for Health and Care Research (NF-SI-0611-10154)
- Leukaemia and Lymphoma Research
- Hutchison Whampoa Limited
- Directorate for Biological Sciences
- Canadian Institutes of Health Research
- Medical Research Council (MR/M008975/1, MC_PC_12009)
- Biotechnology and Biological Sciences Research Council (BB/I00050X/1)
- Cambridge Institute for Medical Research, University of Cambridge
- NIHR Cambridge Biomedical Research Centre
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- hematopoietic stem cells, stem cell heterogeneity, self-renewal, single-cell RNA sequencing, single-cell transplantation, gene expression profiling, stem cell function
- MeSH terms
- Animals, Cell Differentiation, Clone Cells, Gene Expression Regulation, Hematopoietic Stem Cells, Humans, Mice, Inbred C57BL, Genome, Hematopoietic Stem Cell Transplantation, Cell Lineage, Gene Expression Profiling, Cell Proliferation, Single-Cell Analysis
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