Single-cell multi-omics map of human fetal blood in Down syndrome
Open accessAbstract
Down syndrome predisposes individuals to haematological abnormalities, such as increased number of erythrocytes and leukaemia in a process that is initiated before birth and is not entirely understood1–3. Here, to understand dysregulated haematopoiesis in Down syndrome, we integrated single-cell transcriptomics of over 1.1 million cells with chromatin accessibility and spatial transcriptomics datasets using human fetal liver and bone marrow samples from 3 fetuses with disomy and 15 fetuses with trisomy. We found that differences in gene expression in Down syndrome were dependent on both cell type and environment. Furthermore, we found multiple lines of evidence that haematopoietic stem cells (HSCs) in Down syndrome are ‘primed’ to differentiate. We subsequently established a Down syndrome-specific map linking non-coding elements to genes in disomic and trisomic HSCs using 10X multiome data. By integrating this map with genetic variants associated with blood cell counts, we discovered that trisomy restructured regulatory interactions to dysregulate enhancer activity and gene expression critical to erythroid lineage differentiation. Furthermore, as mutations in Down syndrome display a signature of oxidative stress4,5, we validated both increased mitochondrial mass and oxidative stress in Down syndrome, and observed that these mutations preferentially fell into regulatory regions of expressed genes in HSCs. Together, our single-cell, multi-omic resource provides a high-resolution molecular map of fetal haematopoiesis in Down syndrome and indicates significant regulatory restructuring giving rise to co-occurring haematological conditions. Using single-cell and multi-omics data of fetal blood, a high-resolution molecular map of dysregulated haematopoiesis in Down syndrome is provided.
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These findings underscore a global epigenetic rewiring beyond localized chromosomal effects, aligning with prior observations of genomewide Ts21 chromatin reorganization.
“These findings underscore a global epigenetic rewiring beyond localized chromosomal effects, aligning with prior observations of genomewide Ts21 chromatin reorganization (24-26).”
From Molecular and cellular processes disrupted in the early postnatal Down syndrome prefrontal cortex (2026) · cites this paper as [26]
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limma powers differential expression analyses for RNA-sequencing and microarray studies
Ritchie, M. E., Phipson, B., Wu, D., Hu, Y., Law, C. W., Shi, W., & Smyth, G. K. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv007 · Cited by 40,458 · see citing works
Fast, sensitive and accurate integration of single-cell data with Harmony
Korsunsky, I., Millard, N., Fan, J., Slowikowski, K., Zhang, F., Wei, K., Baglaenko, Y., Brenner, M., Loh, P.-R., & Raychaudhuri, S. (2019) · Nature Methods · doi:10.1038/s41592-019-0619-0 · Cited by 10,488 · see citing works
SCANPY: large-scale single-cell gene expression data analysis
Wolf, F. A., Angerer, P., & Theis, F. J. (2018) · Genome Biology · doi:10.1186/s13059-017-1382-0 · Cited by 8,881 · see citing works
Spatial reconstruction of single-cell gene expression data
Satija, R., Farrell, J. A., Gennert, D., Schier, A. F., & Regev, A. (2015) · Nature Biotechnology · doi:10.1038/nbt.3192 · Cited by 7,055 · cited 2× · see citing works
“0.3) implementation 56 .”
MethodInfluentialDissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq
Tirosh, I., Izar, B., Prakadan, S. M., Wadsworth, M. H., Treacy, D., Trombetta, J. J., Rotem, A., Rodman, C., Lian, C., Murphy, G., et al. (2016) · Science · doi:10.1126/science.aad0501 · Cited by 4,944 · see citing works
Generalizing RNA velocity to transient cell states through dynamical modeling
Bergen, V., Lange, M., Peidli, S., Wolf, F. A., & Theis, F. J. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0591-3 · Cited by 2,951 · see citing works
Scrublet: computational identification of cell doublets in single-cell transcriptomic data
Wolock, S. L., Lopez, R., & Klein, A. M. (2018) · doi:10.1101/357368 · Cited by 2,758 · cited 1× · see citing works
“We further applied Scrublet 55 to remove potential doublets.”
MethodScrublet: computational identification of cell doublets in single-cell transcriptomic data
Wolock, S. L., Lopez, R., & Klein, A. M. (2019) · Cell Systems · doi:10.1016/j.cels.2018.11.005 · Cited by 2,758 · see citing works
Deep generative modeling for single-cell transcriptomics
Lopez, R., Regier, J., Cole, M. B., Jordan, M. I., & Yosef, N. (2018) · Nature Methods · doi:10.1038/s41592-018-0229-2 · Cited by 2,530 · see citing works
Expanded encyclopaedias of DNA elements in the human and mouse genomes
The ENCODE Project Consortium, Abascal, F., Acosta, R., Addleman, N. J., Adrian, J., Afzal, V., Ai, R., Aken, B., Akiyama, J. A., Jammal, O. A., et al. (2020) · Nature · doi:10.1038/s41586-020-2493-4 · Cited by 2,378 · see citing works
JASPAR 2022: the 9th release of the open-access database of transcription factor binding profiles
Castro-Mondragon, J. A., Riudavets-Puig, R., Rauluseviciute, I., Berhanu Lemma, R., Turchi, L., Blanc-Mathieu, R., Lucas, J., Boddie, P., Khan, A., Manosalva Pérez, N., et al. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkab1113 · Cited by 1,935 · see citing works
Single-cell chromatin state analysis with Signac
Stuart, T., Srivastava, A., Madad, S., Lareau, C. A., & Satija, R. (2021) · Nature Methods · doi:10.1038/s41592-021-01282-5 · Cited by 1,769 · see citing works
FoxOs Are Critical Mediators of Hematopoietic Stem Cell Resistance to Physiologic Oxidative Stress
Tothova, Z., Kollipara, R., Huntly, B. J., Lee, B. H., Castrillon, D. H., Cullen, D. E., McDowell, E. P., Lazo-Kallanian, S., Williams, I. R., Sears, C., et al. (2007) · Cell · doi:10.1016/j.cell.2007.01.003 · Cited by 1,562 · see citing works
Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells
Ito, K., Hirao, A., Arai, F., Takubo, K., Matsuoka, S., Miyamoto, K., Ohmura, M., Naka, K., Hosokawa, K., Ikeda, Y., et al. (2006) · Nature Medicine · doi:10.1038/nm1388 · Cited by 1,362 · see citing works
Cell2location maps fine-grained cell types in spatial transcriptomics
Kleshchevnikov, V., Shmatko, A., Dann, E., Aivazidis, A., King, H. W., Li, T., Elmentaite, R., Lomakin, A., Kedlian, V., Gayoso, A., et al. (2022) · Nature Biotechnology · doi:10.1038/s41587-021-01139-4 · Cited by 1,279 · see citing works
Chen, Y., Lun, A. T. L., & Smyth, G. K. (2016) · F1000Research · doi:10.12688/f1000research.8987.2 · Cited by 1,247 · see citing works
Activity-by-contact model of enhancer–promoter regulation from thousands of CRISPR perturbations
Fulco, C. P., Nasser, J., Jones, T. R., Munson, G., Bergman, D. T., Subramanian, V., Grossman, S. R., Anyoha, R., Doughty, B. R., Patwardhan, T. A., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0538-0 · Cited by 1,111 · see citing works
Lun, A. T. L., Riesenfeld, S. J., Andrews, T. S., Dao, T. P., Gomes, T., Jamboree, P. I. T. 1. H. C. A., & Marioni, J. C. (2019) · Genome biology · doi:10.1186/s13059-019-1662-y · Cited by 1,042 · see citing works
Confronting false discoveries in single-cell differential expression
Squair, J. W., Gautier, M., Kathe, C., Anderson, M. A., James, N. D., Hutson, T. H., Hudelle, R., Qaiser, T., Matson, K. J. E., Barraud, Q., et al. (2021) · doi:10.1101/2021.03.12.435024 · Cited by 1,017 · 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
Risks of leukaemia and solid tumours in individuals with Down's syndrome
Hasle, H., Clemmensen, I. H., & Mikkelsen, M. (2000) · The Lancet · doi:10.1016/s0140-6736(99)05264-2 · Cited by 898 · see citing works
VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease
Kim, J., Gupta, R., Blanco, L. P., Yang, S., Shteinfer-Kuzmine, A., Wang, K., Zhu, J., Yoon, H. E., Wang, X., Kerkhofs, M., et al. (2019) · Science · doi:10.1126/science.aav4011 · Cited by 793 · see citing works
Down syndrome phenotypes: the consequences of chromosomal imbalance.
Korenberg, J. R., Chen, X. N., Schipper, R. D., Sun, Z., Gonsky, R., Gerwehr, S., Carpenter, N. J., Däumer, C., Dignan, P. S. J., & Distèche, C. M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.11.4997 · Cited by 784 · see citing works
CellRank for directed single-cell fate mapping
Lange, M., Bergen, V., Klein, M., Setty, M. N., Reuter, B., Bakhti, M., Lickert, H., Ansari, M., Gote-Schniering, J., Schiller, H. B., et al. (2022) · Nature Methods · doi:10.1038/s41592-021-01346-6 · Cited by 734 · see citing works
The Polygenic and Monogenic Basis of Blood Traits and Diseases
Vuckovic, D., Bao, E. L., Akbari, P., Lareau, C. A., Mousas, A., Jiang, T., Chen, M.-H., Raffield, L. M., Tardaguila, M., Huffman, J. E., et al. (2020) · Cell · doi:10.1016/j.cell.2020.08.008 · Cited by 671 · see citing works
Decoding human fetal liver haematopoiesis
Popescu, D.-M., Botting, R. A., Stephenson, E., Green, K., Webb, S., Jardine, L., Calderbank, E. F., Polanski, K., Goh, I., Efremova, M., et al. (2019) · Nature · doi:10.1038/s41586-019-1652-y · Cited by 606 · see citing works
(2007) · doi:10.1289/ehp.9023 · Cited by 591 · see citing works
Cell-of-origin chromatin organization shapes the mutational landscape of cancer
Polak, P., Karlić, R., Koren, A., Thurman, R., Sandstrom, R., Lawrence, M. S., Reynolds, A., Rynes, E., Vlahoviček, K., Stamatoyannopoulos, J. A., et al. (2015) · Nature · doi:10.1038/nature14221 · Cited by 557 · see citing works
Kokoszka, J. E., Coskun, P. E., Esposito, L., & Wallace, D. C. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.051627098 · Cited by 488 · see citing works
Pendergrass, W., Wolf, N. S., & Poot, M. J. M. (2004) · Cytometry Part A · doi:10.1002/cyto.a.20033 · Cited by 476 · see citing works
Kondo, T., Kobayashi, J., Saitoh, T., Maruyama, K., Ishii, K. J., Barber, G. N., Komatsu, K., Akira, S., & Kawai, T. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1222694110 · Cited by 346 · see citing works
VCP/p97 cooperates with YOD1, UBXD1 and PLAA to drive clearance of ruptured lysosomes by autophagy
Papadopoulos, C., Kirchner, P., Bug, M., Grum, D., Koerver, L., Schulze, N., Pöhler, R., Dressler, A., Fengler, S., Arhzaouy, K., et al. (2016) · The EMBO Journal · doi:10.15252/embj.201695148 · Cited by 341 · see citing works
Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Human Developmental Hematopoiesis
Ranzoni, A. M., Tangherloni, A., Berest, I., Riva, S. G., Myers, B., Strzelecka, P. M., Xu, J., Panada, E., Mohorianu, I., Zaugg, J. B., et al. (2021) · Cell Stem Cell · doi:10.1016/j.stem.2020.11.015 · Cited by 331 · see citing works
Self-citationGATA1 mutations in transient leukemia and acute megakaryoblastic leukemia of Down syndrome
Hitzler, J. K., Cheung, J., Li, Y., Scherer, S. W., & Zipursky, A. (2003) · Blood · doi:10.1182/blood-2003-01-0013 · Cited by 323 · see citing works
The eukaryotic promoter database in its 30th year: focus on non-vertebrate organisms
Dreos, R., Ambrosini, G., Groux, R., Périer, R. C., & Bücher, P. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw1069 · Cited by 275 · see citing works
Down syndrome and the complexity of genome dosage imbalance
Antonarakis, S. (2016) · Nature reviews genetics · doi:10.1038/nrg.2016.154 · Cited by 264 · see citing works
The effects of chromatin organization on variation in mutation rates in the genome
Makova, K. D., & Hardison, R. C. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3890 · Cited by 250 · see citing works
Cumulus provides cloud-based data analysis for large-scale single-cell and single-nucleus RNA-seq
Li, B., Gould, J., Yang, Y., Sarkizova, S., Tabaka, M., Ashenberg, O., Rosen, Y., Slyper, M., Kowalczyk, M. S., Villani, A., et al. (2020) · Nature Methods · doi:10.1038/s41592-020-0905-x · Cited by 235 · see citing works
Kornblum, C., Nicholls, T. J., Haack, T. B., Schöler, S., Peeva, V., Danhauser, K., Hallmann, K., Zsurka, G., Rorbach, J., Iuso, A., et al. (2013) · Nature Genetics · doi:10.1038/ng.2501 · Cited by 232 · see citing works
Vannini, N., Campos, V., Girotra, M., Trachsel, V., Rojas-Sutterlin, S., Tratwal, J., Ragusa, S., Stefanidis, E., Ryu, D., Rainer, P. Y., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.02.012 · Cited by 218 · see citing works
Interrogation of human hematopoiesis at single-cell and single-variant resolution
Ulirsch, J. C., Lareau, C. A., Bao, E. L., Ludwig, L. S., Guo, M. H., Benner, C., Satpathy, A. T., Kartha, V. K., Salem, R. M., Hirschhorn, J. N., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0362-6 · Cited by 208 · see citing works
RNF26 Temporally Regulates Virus-Triggered Type I Interferon Induction by Two Distinct Mechanisms
Qin, Y., Zhou, M., Hu, M., Hu, Y.-H., Zhang, J., Guo, L., Zhong, B., & Shu, H. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1004358 · Cited by 203 · see citing works
Mitochondrial Potentiation Ameliorates Age-Related Heterogeneity in Hematopoietic Stem Cell Function
Mansell, E., Sigurðsson, V., Deltcheva, E. M., Brown, J., James, C. T., Miharada, K., Soneji, S., Larsson, J. T., & Enver, T. (2020) · Cell stem cell · doi:10.1016/j.stem.2020.09.018 · Cited by 176 · see citing works
Perturbation of fetal liver hematopoietic stem and progenitor cell development by trisomy 21
Roy, A., Cowan, G., Mead, A. J., Filippi, S. L., Bohn, G., Chaidos, A., Tunstall, O., Chan, J. K. Y., Choolani, M. A., Bennett, P. R., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1211405109 · Cited by 166 · see citing works
Blood and immune development in human fetal bone marrow and Down syndrome
Jardine, L., Webb, S., Goh, I., Londoño, M. Q., Reynolds, G., Mather, M. W., Olabi, B., Stephenson, E., Botting, R. A., Horsfall, D., et al. (2021) · Nature · doi:10.1038/s41586-021-03929-x · Cited by 163 · see citing works
DNA polymerase-α regulates the activation of type I interferons through cytosolic RNA:DNA synthesis
Starokadomskyy, P., Gemelli, T., Rios, J. J., Xing, C., Wang, R. C., Li, H., Pokatayev, V., Dozmorov, I. M., Khan, S., Miyata, N., et al. (2016) · Nature Immunology · doi:10.1038/ni.3409 · Cited by 146 · see citing works
Lineage tracing of human development through somatic mutations
Spencer-Chapman, M., Ranzoni, A. M., Myers, B., Williams, N., Coorens, T., Mitchell, E., Butler, T., Dawson, K., Hooks, Y., Moore, L., et al. (2021) · Nature · doi:10.1038/s41586-021-03548-6 · Cited by 138 · see citing works
Self-citationMutations in DNA2 Link Progressive Myopathy to Mitochondrial DNA Instability
Ronchi, D., Fonzo, A. D., Lin, W., Bordoni, A., Liu, C., Fassone, E., Pagliarani, S., Rizzuti, M., Zheng, L., Filosto, M., et al. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.12.014 · Cited by 136 · see citing works
Valenti, D., Manente, G. A., Moro, L., Marra, E., & Vacca, R. A. (2011) · Biochemical Journal · doi:10.1042/bj20101908 · Cited by 133 · see citing works
SMiLE-seq identifies binding motifs of single and dimeric transcription factors
Isakova, A., Groux, R., Imbeault, M., Rainer, P. Y., Alpern, D., Dainese, R., Ambrosini, G., Trono, D., Bücher, P., & Deplancke, B. (2017) · Nature Methods · doi:10.1038/nmeth.4143 · Cited by 114 · see citing works
Somatic mutation distributions in cancer genomes vary with three-dimensional chromatin structure
Akdemir, K. C., Le, V. T., Kim, J. M., Killcoyne, S., King, D. A., Lin, Y., Tian, Y., Inoue, A., Amin, S. B., Robinson, F. S., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-0708-0 · Cited by 112 · see citing works
monaLisa: an R/Bioconductor package for identifying regulatory motifs
Machlab, D., Burger, L., Soneson, C., Rijli, F. M., Schübeler, D., & Stadler, M. B. (2022) · Bioinformatics · doi:10.1093/bioinformatics/btac102 · Cited by 109 · see citing works
Izzo, A., Nitti, M. P., Mollo, N., Paladino, S., Procaccini, C., Faicchia, D., Calı̀, G., Genesio, R., Bonfiglio, F., Cicatiello, R., et al. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx016 · Cited by 100 · see citing works
Down-syndrome-induced senescence disrupts the nuclear architecture of neural progenitors
Meharena, H. S., Marco, A., Dileep, V., Lockshin, E. R., Akatsu, G. Y., Mullahoo, J., Watson, L. A., Ko, T., Guerin, L. N., Abdurrob, F., et al. (2022) · Cell Stem Cell · doi:10.1016/j.stem.2021.12.002 · Cited by 92 · see citing works
Ubiquilin-1 Protects Cells from Oxidative Stress and Ischemic Stroke Caused Tissue Injury in Mice
Liu, Y., Lü, L., Hettinger, C. L., Dong, G., Zhang, D., Rezvani, K. S., Wang, X., & Wang, H. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.3541-13.2014 · Cited by 86 · see citing works
Tun-Kyi, A., Finn, G., Greenwood, A., Nowak, M. A., Lee, T. H., Asara, J. M., Tsokos, G. C., Fitzgerald, K., Israel, E., Li, X., et al. (2011) · Nature Immunology · doi:10.1038/ni.2069 · Cited by 83 · see citing works
Laurent, A. P., Kotecha, R. S., & Malinge, S. (2020) · Leukemia · doi:10.1038/s41375-020-0854-5 · Cited by 82 · see citing works
MIRA: joint regulatory modeling of multimodal expression and chromatin accessibility in single cells
Lynch, A. W., Theodoris, C. V., Long, H. W., Brown, M., Liu, X. S., & Meyer, C. A. (2022) · Nature Methods · doi:10.1038/s41592-022-01595-z · Cited by 80 · see citing works
Variant to function mapping at single-cell resolution through network propagation
Yu, F., Cato, L. D., Weng, C., Liggett, L. A., Jeon, S., Xu, K., Chiang, C. W. K., Wiemels, J. L., Weissman, J. S., de Smith, A. J., et al. (2022) · Nature Biotechnology · doi:10.1038/s41587-022-01341-y · Cited by 73 · see citing works
Mutational spectrum at GATA1 provides insights into mutagenesis and leukemogenesis in Down syndrome
Cabelof, D. C., Patel, H., Chen, Q., Remmen, H. V., Matherly, L. H., Ge, Y., & Taub, J. W. (2009) · Blood · doi:10.1182/blood-2008-11-190330 · Cited by 71 · see citing works
Mapping the cellular origin and early evolution of leukemia in Down syndrome
Wagenblast, E., Araújo, J., Gan, O., Cutting, S. K., Murison, A., Krivdova, G., Azkanaz, M., McLeod, J., Smith, S. A., Gratton, B. A., et al. (2021) · Science · doi:10.1126/science.abf6202 · Cited by 68 · see citing works
Expanded encyclopaedias of DNA elements in the human and mouse genomes.
Moore, J. E., Purcaro, M. J., Pratt, H., Epstein, C. B., Noam Shoresh, F., Adrian, J., Kawli, T., Davis, C., Dobin, A., Kaul, R., et al. (2020) · Open Access CRIS of the University of Bern · doi:10.7892/boris.146110 · Cited by 66 · see citing works
Defective mitochondrial protease LonP1 can cause classical mitochondrial disease
Peter, B., Waddington, C. L., Oláhová, M., Sommerville, E. W., Hopton, S., Pyle, A., Champion, M., Ohlson, M., Siibak, T., Chrzanowska-Lightowlers, Z. M. A., et al. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy080 · Cited by 66 · see citing works
The Polygenic and Monogenic Basis of Blood Traits and DiseasesPreprint
Vuckovic, D., Bao, E. L., Akbari, P., Lareau, C. A., Mousas, A., Jiang, T., Chen, M., Raffield, L. M., Tardáguila, M., Huffman, J. E., et al. (2020) · medRxiv · doi:10.1101/2020.02.02.20020065 · Cited by 64 · see citing works
Transferrin Receptors in Erythropoiesis
Richard, C., & Verdier, F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249713 · Cited by 61 · see citing works
Binding Features and Functions of ATG3
Fang, D., Xie, H., Hu, T., Shan, H., & Li, M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.685625 · Cited by 60 · see citing works
Tissue-specific enhancer–gene maps from multimodal single-cell data identify causal disease alleles
Sakaue, S., Weinand, K., Isaac, S., Dey, K. K., Jagadeesh, K. A., Kanai, M., Watts, G. F. M., Zhu, Z., Accelerating Medicines Partnership® RA/SLE Program and Network, Albrecht, J., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01682-1 · Cited by 60 · see citing works
The genome-wide impact of trisomy 21 on DNA methylation and its implications for hematopoiesis
Muskens, I. S., Li, S., Jackson, T., Elliott, N., Hansen, H. M., Myint, S. S., Pandey, P., Schraw, J. M., Roy, R., Anguiano, J., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21064-z · Cited by 59 · see citing works
Mitochondrial regulation of hematopoietic stem cells
Snoeck, H. (2017) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2017.12.010 · Cited by 47 · see citing works
Oxidative DNA damage in bone marrow cells of patients with low-risk myelodysplastic syndrome
Novotná, B., Bagryantseva, Y., Šišková, M., & Neuwirtová, R. (2008) · Leukemia Research · doi:10.1016/j.leukres.2008.07.005 · Cited by 45 · see citing works
Hematopoietic disorders in Down syndrome.
Choi, J. K. (2008) · PubMed Central · Cited by 33 · see citing works
Hasaart, K., Manders, F., van der Hoorn, M., Verheul, M., Poplonski, T., Kuijk, E., Lopes, S. M. C. D. S., & van Boxtel, R. (2020) · Scientific Reports · doi:10.1038/s41598-020-69822-1 · Cited by 27 · see citing works
Guo, P., Chen, S., Li, D., Zhang, J., Luo, J., Zhang, A., Yu, D., Bloom, M. S., Chen, L., & Chen, W. (2020) · Environmental Pollution · doi:10.1016/j.envpol.2020.114160 · Cited by 21 · see citing works
Bagchi, A., Devaraju, N., Chambayil, K., Rajendiran, V., Venkatesan, V., Sayed, N., Pai, A. A., Nath, A., David, E. K., Nakamura, Y., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-13783-0 · Cited by 8 · see citing works
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Molecular and cellular processes disrupted in the early postnatal Down syndrome prefrontal cortex
Risgaard, R. D., Hanthanan Arachchilage, K., Knaack, S. A., Hosseini, M., Chen, R. J., Kumarage, P., Schmidt, D. K., Huang, X., Sheng, J., Wang, C. J., et al. (2026) · Science · doi:10.1126/science.aea1549 · Cited by 12 · see citing works
Clinical significance of preleukemic somatic GATA1 mutations in children with Down syndrome
Elliott, N., Bhatnagar, N., Buck, G., Hernandez, D. C., Perkins, K., de Smith, A. J., Chaussade, A., Nizery, L., Metzner, M., Garnett, C., et al. (2025) · Blood · doi:10.1182/blood.2025029250 · Cited by 7 · see citing works
Zheng, J., Yang, Q., Liu, H., Zhao, H., Wang, S., Liu, Y., Wu, X., Ding, Y., Ying, H., Ye, Y., et al. (2025) · Advanced Science · doi:10.1002/advs.202507451 · Cited by 6 · see citing works
Marderstein, A. R., Kundu, S., Padhi, E. M., Deshpande, S., Wang, A., Robb, E., Sun, Y., Yun, C. M., Pomales-Matos, D. A., Xie, Y., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.02.18.638922 · Cited by 6 · see citing works
Self-citationAlasmari, F. F., Ahmad, A., Alsanea, S., Hammad, A. M., & Al-Qerem, W. A. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1592277 · Cited by 5 · see citing works
Neurodevelopmental origins of age-related neurodegenerative diseases
Chow, H., & Abel, T. G. (2026) · EBioMedicine · doi:10.1016/j.ebiom.2026.106151 · Cited by 5 · see citing works
Decoding common and rare noncoding variant effects across cellular and developmental contexts
Marderstein, A. R., Kundu, S., Padhi, E. M., Deshpande, S., Wang, A., Robb, E., Sun, Y., Yun, C. M., Pomales-Matos, D. A., Xie, Y., et al. (2026) · Nature Genetics · doi:10.1038/s41588-026-02619-6 · Cited by 9 · see citing works
Self-citationGenome-wide association study of somatic GATA1s mutations in newborns with Down syndrome
Li, Y.-Q., Elliott, N., Lein, P., Vyas, P., Roberts, I., & de Smith, A. D. (2025) · Blood Advances · doi:10.1182/bloodadvances.2025016282 · Cited by 2 · see citing works
Takasaki, K., Wafula, E. K., Fan, J., Sit, Y. T., Kumar, S. S., Smith, D. L., Gagne, A. L., Gearhart, P. A., French, D. L., Thom, C. S., et al. (2025) · Stem Cell Reports · doi:10.1016/j.stemcr.2025.102577 · Cited by 3 · see citing works
Dong, R., Wang, G., Shi, Y., Gao, J., Hu, W.-L., & Zhang, T. (2025) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2025.159692 · Cited by 2 · see citing works
Spatially resolved multiomics of human meningeal development reveal lineage and disease dynamics
To, K., Pett, J. P., Dufva, O., Chipampe, N.-J., Polański, K., Cujba, A.-M., Roberts, K., Predeus, A. V., Yayon, N., Kanemaru, K., et al. (2026) · Nature Cell Biology · doi:10.1038/s41556-026-02075-8 · Cited by 2 · see citing works
Zhong, C., & Zhong, L. (2025) · PLoS ONE · doi:10.1371/journal.pone.0322326 · Cited by 2 · see citing works
Perspectives on the origin and therapeutic opportunities in Down syndrome-associated leukemia
Panchal, K., Armitage, J. D., Cheung, L. C., Kotecha, R. S., & Malinge, S. (2025) · Cancer and Metastasis Reviews · doi:10.1007/s10555-025-10291-1 · Cited by 1 · see citing works
Impact of Chromosomal Instability and Aneuploidy in Cancer Development
Mennie, A. K., Dhital, B., & Ly, P. (2025) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-071124-101613 · Cited by 1 · see citing works
Chromatin accessibility shapes development-specific lineage plasticity in hematopoiesis
Palo, S., Nagaharu, K., Sommarin, M. N. E., Olofzon, R., Turati, V. A., Soneji, S., Karlsson, G., & Böiers, C. (2026) · Blood Advances · doi:10.1182/bloodadvances.2026019909 · Cited by 1 · see citing works
Multi-omics investigation of thyroid development and dysfunction in down syndrome
Lauffer, P., Zwaveling‐Soonawala, N., Yim, A. Y. F. L., van der Laan, L., van Zelderen‐Bhola, S. L., Venema, A., Mul, A. N. P. M., Bugiani, M., Rijnstra, E. S.-V., Gunst, Q. D., et al. (2026) · Human Molecular Genetics · doi:10.1093/hmg/ddag005 · Cited by 1 · see citing works
Now You See Me: Visualizing nuclear complexity by selective staining
Casali, C., Cavallo, M., Diaf, A., Milanesi, G., & Biggiogera, M. (2026) · Methods · doi:10.1016/j.ymeth.2026.03.005 · Cited by 1 · see citing works
Single cell transcriptional evolution of myeloid leukemia of Down syndrome
Trinh, M. K., Schuschel, K., Issa, H., Thomas, R., Parks, C., Oszlánczi, Á., Ogbonnah, T., Zhou, D., Mamanova, L., Prigmore, E., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-71707-2 · Cited by 1 · see citing works
Mouli, K., Liopo, A. V., Wang, H., Suva, L. J., Olson, K. R., Derry, P. J., & Kent, T. A. (2026) · Scientific Reports · doi:10.1038/s41598-026-45627-6 · Cited by 1 · see citing works
Childhood leukaemia in Down’s syndrome primed by blood-cell bias
Malinge, S. (2024) · Nature · doi:10.1038/d41586-024-02785-9 · Cited by 1 · see citing works
PARP1 suppression drives ROS resistance in aneuploid cancer cells
Cheng, P., Mermerian, A., Wang, Y., Chen, Z., Quysbertf, H. M., Cheema, P. S., Mays, J. C., Zhao, X., Katsnelson, L., Mei, S., et al. (2026) · Molecular Cell · doi:10.1016/j.molcel.2026.04.006
Aberrant chromatin remodeling influences human neural cell fate change in Trisomy 21Preprint
Klein, J. A., Upadhya, S., Nathanson, A. J., Silvian, D., Zaniewski, E. F., Morris, R., Haas, W., & Barrett, L. E. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.01.729170
Solari-Hernández, S., González-Madrid, E., González, P. A., Bueno, S. M., & Kalergis, A. M. (2026) · Journal of Clinical Immunology · doi:10.1007/s10875-026-02054-6
Peroni, E., Amato, R., Bado, M., Favarato, M., & Rosato, A. (2026) · Experimental Hematology and Oncology · doi:10.1186/s40164-026-00815-y
Single-cell profiling of mitochondrial phenotyping–coupled mtDNA genotyping
Zhang, Z., Zhang, L., An, P., Zhang, X., Xia, Y., Kang, Y., Chen, X., Hua, R., Zhu, Y., Hao, Y., et al. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2531151123
Disrupted chromatin architecture blocks B lymphopoiesis in Down syndromePreprint
Liao, Z., Zhang, M., Soong, B. Y., Zhu, B., Boshans, L. L., Wang, K., Quijada‐Álamo, M., Osakwe, I., Wang, Z., Fiore, P., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.07.757425
- Authors
- Marderstein, A. R., De Zuani, M., Moeller, R., Bezney, J., Padhi, E. M., Wong, S., Coorens, T. H. H., Xie, Y., Xue, H., Montgomery, S. B., & Cvejic, A.
- Affiliations
- Stanford Medicine (US)
- University of Copenhagen (DK)
- Stanford University (US)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- Broad Institute (US)
- Corresponding author
- Cvejic, Ana
- ORCID
- Venue
- Nature
- Published
- 2024-09-25
- Volume
- 634
- Issue
- 8032
- Pages
- 104-112
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC11446839
- OpenAlex
- W4402826841
- Cited by
- 26
- References
- 75
- Citations by year
- 2026: 15 · 2025: 10 · 2024: 1
- FWCI
- 10.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- Apollo (University of Cambridge) (submittedVersion, cc-by-nc-nd)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Wellcome Trust (MR/006237/1, 203151/Z/16/Z)
- National Institute for Health and Care Research
- Novo Nordisk Fonden (NNF21OC0066260)
- Medical Research Council (MR/R006237/1)
- National Human Genome Research Institute (U01HG011762)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- Down syndrome, hematopoietic stem cells, erythroid differentiation, enhancer activity, chromatin accessibility, non-coding regulatory elements, oxidative stress, mitochondrial mass, fetal liver, fetal bone marrow, hematological abnormalities, single-cell multi-omics
- MeSH terms
- Multiomics, Blood Cell Count, Bone Marrow, Cell Differentiation, Chromatin, Down Syndrome, Female, Fetal Blood, Fetus, Hematopoiesis, Hematopoietic Stem Cells, Humans, Liver, Mitochondria, Mutation, Trisomy, Reproducibility of Results, Oxidative Stress, Cell Lineage, Gene Expression Profiling, Single-Cell Analysis, Transcriptome
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