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Single-cell multi-omics of human clonal hematopoiesis reveals that DNMT3A R882 mutations perturb early progenitor states via selective hypomethylation

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  • Martincorena, I. et al. Somatic mutant clones colonize the human esophagus with age. Science 362, 911–917 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yizhak, Okay. et al. RNA sequence evaluation reveals macroscopic somatic clonal growth throughout regular tissues. Science 364, eaaw0726 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yokoyama, A. et al. Age-related remodelling of oesophageal epithelia by mutated most cancers drivers. Nature 565, 312–317 (2019).

    CAS 
    PubMed 

    Google Scholar 

  • Yoshida, Okay. et al. Tobacco smoking and somatic mutations in human bronchial epithelium. Nature 578, 266–272 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Martincorena, I. et al. Excessive burden and pervasive constructive collection of somatic mutations in regular human pores and skin. Science 348, 880–886 (2015).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Mustjoki, S. & Younger, N. S. Somatic mutations in ‘benign’ illness. N. Engl. J. Med. 384, 2039–2052 (2021).

    CAS 
    PubMed 

    Google Scholar 

  • Shlush, L. I. et al. Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature 506, 328–333 (2014).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Jaiswal, S. et al. Age-related clonal hematopoiesis related to hostile outcomes. N. Engl. J. Med. 371, 2488–2498 (2014).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Genovese, G. et al. Clonal hematopoiesis and blood-cancer threat inferred from blood DNA sequence. N. Engl. J. Med. 371, 2477–2487 (2014).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Xie, M. et al. Age-related mutations related to clonal hematopoietic growth and malignancies. Nat. Med. 20, 1472–1478 (2014).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Steensma, D. P. et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood 126, 9–16 (2015).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Younger, A. L., Challen, G. A., Birmann, B. M. & Druley, T. E. Clonal haematopoiesis harbouring AML-associated mutations is ubiquitous in wholesome adults. Nat. Commun. 7, 12484 (2016).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zink, F. et al. Clonal hematopoiesis, with and with out candidate driver mutations, is widespread within the aged. Blood 130, 742–752 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Champion, Okay. M., Gilbert, J. G. R., Asimakopoulos, F. A., Hinshelwood, S. & Inexperienced, A. R. Clonal haemopoiesis in regular aged ladies: implications for the myeloproliferative problems and myelodysplastic syndromes. Br. J. Haematol. 97, 920–926 (1997).

    CAS 
    PubMed 

    Google Scholar 

  • SanMiguel, J. M. et al. Cell-extrinsic stressors from the ageing bone marrow (BM) microenvironment promote Dnmt3a-mutant clonal hematopoiesis. Blood 134 (Suppl), 5 (2019).

    Google Scholar 

  • Terao, C. et al. Chromosomal alterations amongst age-related haematopoietic clones in Japan. Nature 584, 130–135 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Watson, C. J. et al. The evolutionary dynamics and health panorama of clonal hematopoiesis. Science 367, 1449–1454 (2020).

    CAS 
    PubMed 

    Google Scholar 

  • Teixeira, V. H. et al. Deciphering the genomic, epigenomic, and transcriptomic landscapes of pre-invasive lung most cancers lesions. Nat. Med. 25, 517–525 (2019).

    CAS 
    PubMed 

    Google Scholar 

  • Steensma, D. P. & Ebert, B. L. Clonal hematopoiesis as a mannequin for premalignant modifications throughout ageing. Exp. Hematol. 83, 48–56 (2020).

    PubMed 

    Google Scholar 

  • Desai, P. et al. Somatic mutations precede acute myeloid leukemia years earlier than prognosis. Nat. Med. 24, 1015–1023 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Papaemmanuil, E. et al. Medical and organic implications of driver mutations in myelodysplastic syndromes. Blood 122, 3616–3627 (2013).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Abelson, S. et al. Prediction of acute myeloid leukaemia threat in wholesome people. Nature 559, 400–404 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Buscarlet, M. et al. DNMT3A and TET2 dominate clonal hematopoiesis and display benign phenotypes and totally different genetic predispositions. Blood 130, 753–762 (2017).

    CAS 
    PubMed 

    Google Scholar 

  • Younger, A. L., Spencer Tong, R., Birmann, B. M. & Druley, T. E. Clonal hematopoiesis and threat of acute myeloid leukemia. Haematologica 104, 2410–2417 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Jeong, M. et al. Lack of Dnmt3a immortalizes hematopoietic stem cells in vivo. Cell Rep. 23, 1–10 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ostrander, E. L. et al. Divergent results of Dnmt3a and Tet2 mutations on hematopoietic progenitor cell health. Stem Cell Rep. 14, 551–560 (2020).

    CAS 

    Google Scholar 

  • Koya, J. et al. DNMT3A R882 mutants work together with polycomb proteins to dam haematopoietic stem and leukaemic cell differentiation. Nat. Commun. 7, 10924 (2016).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kim, S. J. et al. A DNMT3A mutation widespread in AML displays dominant-negative results in murine ES cells. Blood 122, 4086–4089 (2013).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Russler-Germain, D. A. et al. The R882H DNMT3A mutation related to AML dominantly inhibits wild-type DNMT3A by blocking its capability to type lively tetramers. Most cancers Cell 25, 442–454 (2014).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Nam, A. S. et al. Somatic mutations and cell id linked by genotyping of transcriptomes. Nature 571, 355–360 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gaiti, F. et al. Epigenetic evolution and lineage histories of power lymphocytic leukaemia. Nature 569, 576–580 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Mouhieddine, T. H. et al. Clonal hematopoiesis is related to hostile outcomes in a number of myeloma sufferers present process transplant. Nat. Commun. 11, 2996 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Smith, T., Heger, A. & Sudbery, I. UMI-tools: modeling sequencing errors in Distinctive Molecular Identifiers to enhance quantification accuracy. Genome Res. 27, 491–499 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Tickle, T., Tirosh, I., Georgescu, C., Brown, M. & Haas, B. inferCNV of the Trinity CTAT Venture (Broad Institute of MIT and Harvard, 2019).

  • Stuart, T. et al. Complete integration of single-cell knowledge. Cell 177, 1888–1902 e21 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Pellin, D. et al. A complete single cell transcriptional panorama of human hematopoietic progenitors. Nat. Commun. 10, 2395 (2019).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Challen, G. A. et al. Dnmt3a and Dnmt3b have overlapping and distinct features in hematopoietic stem cells. Cell Stem Cell 15, 350–364 (2014).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Challen, G. A. et al. Dnmt3a is important for hematopoietic stem cell differentiation. Nat. Genet. 44, 23–31 (2011).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Cao, J. et al. The one-cell transcriptional panorama of mammalian organogenesis. Nature 566, 496–502 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Trapnell, C. et al. The dynamics and regulators of cell destiny selections are revealed by pseudotemporal ordering of single cells. Nat. Biotechnol. 32, 381–386 (2014).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Guryanova, O. A. et al. DNMT3A mutations promote anthracycline resistance in acute myeloid leukemia by way of impaired nucleosome transforming. Nat. Med. 22, 1488–1495 (2016).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Velten, L. et al. Human haematopoietic stem cell lineage dedication is a steady course of. Nat. Cell Biol. 19, 271–281 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Tirosh, I. et al. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science 352, 189–196 (2016).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • La Manno, G. et al. RNA velocity of single cells. Nature 560, 494–498 (2018).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Bergen, V., Lange, M., Peidli, S., Wolf, F. A. & Theis, F. J. Generalizing RNA velocity to transient cell states via dynamical modeling. Nat. Biotechnol. 38, 1408–1414 (2020).

    CAS 
    PubMed 

    Google Scholar 

  • Clay, D. et al. CD9 and megakaryocyte differentiation. Blood 97, 1982–1989 (2001).

    CAS 
    PubMed 

    Google Scholar 

  • Noetzli, L. J., French, S. L. & Machlus, Okay. R.New insights into the differentiation of megakaryocytes from hematopoietic progenitors. Arterioscler. Thromb. Vasc. Biol. 39, 1288–1300 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Slupsky, J. R. et al. The platelet antigens CD9, CD42 and integrin alphaIIbbetaIIIa may be topographically related and transduce functionally comparable alerts. Eur. J. Biochem. 244, 168–175 (1997).

    CAS 
    PubMed 

    Google Scholar 

  • Dai, Y. J. et al. Conditional knockin of Dnmt3a R878H initiates acute myeloid leukemia with mTOR pathway involvement. Proc. Natl Acad. Sci. USA 114, 5237–5242 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Thol, F. et al. Incidence and prognostic affect of DNMT3A mutations in acute myeloid leukemia. J. Clin. Oncol. 29, 2889–2896 (2011).

    CAS 
    PubMed 

    Google Scholar 

  • Xu, J. et al. DNMT3A Arg882 mutation drives power myelomonocytic leukemia via disturbing gene expression/DNA methylation in hematopoietic cells. Proc. Natl Acad. Sci. USA 111, 2620–2625 (2014).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Saito, Y. et al. Identification of therapeutic targets for quiescent, chemotherapy-resistant human leukemia stem cells. Sci. Transl. Med. 2, 17ra9 (2010).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Tsuboi, N., Asano, Okay., Lauterbach, M. & Mayadas, T. N. Human neutrophil Fcgamma receptors provoke and play specialised nonredundant roles in antibody-mediated inflammatory illnesses. Immunity 28, 833–846 (2008).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lanier, L. L., Corliss, B. C., Wu, J., Leong, C. & Phillips, J. H. Immunoreceptor DAP12 bearing a tyrosine-based activation motif is concerned in activating NK cells. Nature 391, 703–707 (1998).

    CAS 
    PubMed 

    Google Scholar 

  • Bouchon, A., Hernández-Munain, C., Cella, M. & Colonna, M. A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells. J. Exp. Med. 194, 1111–1122 (2001).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Karulf, M., Kelly, A., Weinberg, A. D. & Gold, J. A. OX40 ligand regulates irritation and mortality within the innate immune response to sepsis. J. Immunol. 185, 4856–4862 (2010).

    CAS 
    PubMed 

    Google Scholar 

  • Leoni, C. et al. Dnmt3a restrains mast cell inflammatory responses. Proc. Natl Acad. Sci. USA 114, E1490–E1499 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Fuster, J. J. et al. Clonal hematopoiesis related to TET2 deficiency accelerates atherosclerosis growth in mice. Science 355, 842–847 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Jaiswal, S. & Libby, P. Clonal haematopoiesis: connecting ageing and irritation in heart problems. Nat. Rev. Cardiol. 17, 137–144 (2019).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Jaiswal, S. et al. Clonal hematopoiesis and threat of atherosclerotic heart problems. N. Engl. J. Med. 377, 111–121 (2017).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Vester, S. Okay. et al. Nucleolin acts because the receptor for C1QTNF4 and helps C1QTNF4-mediated innate immunity modulation. J. Biol. Chem. 296, 100513 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Li, Q. et al. Identification of C1qTNF-related protein 4 as a possible cytokine that stimulates the STAT3 and NF-κB pathways and promotes cell survival in human most cancers cells. Most cancers Lett. 308, 203–214 (2011).

    CAS 
    PubMed 

    Google Scholar 

  • Ramalingam, P. et al. Continual activation of endothelial MAPK disrupts hematopoiesis by way of NFKB dependent inflammatory stress reversible by SCGF. Nat. Commun. 11, 666 (2020).

  • Shen, B. et al. Integrin alpha11 is an Osteolectin receptor and is required for the upkeep of grownup skeletal bone mass. eLife 8, e42274 (2019).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Ito, C. et al. Serum stem cell development issue for monitoring hematopoietic restoration following stem cell transplantation. Bone Marrow Transpl. 32, 391–398 (2003).

    CAS 

    Google Scholar 

  • Wingender, E., Dietze, P., Karas, H. & Knüppel, R. TRANSFAC: a database on transcription elements and their DNA binding websites. Nucleic Acids Res. 24, 238–241 (1996).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ben-Porath, I. et al. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat. Genet. 40, 499–507 (2008).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Coller, H. A. et al. Expression evaluation with oligonucleotide microarrays reveals that MYC regulates genes concerned in development, cell cycle, signaling, and adhesion. Proc. Natl Acad. Sci. USA 97, 3260–3265 (2000).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Delgado, M. D. & León, J. Myc roles in hematopoiesis and leukemia. Genes Most cancers 1, 605–616 (2010).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Guo, Y. et al. c-Myc-mediated management of cell destiny in megakaryocyte–erythrocyte progenitors. Blood 114, 2097–2106 (2009).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Mayers, S. et al. Institution of an erythroid progenitor cell line able to enucleation achieved with an inducible c-Myc vector. BMC Biotech. 19, 21 (2019).

    Google Scholar 

  • Vaisvila, R. et al. Enzymatic methyl sequencing detects DNA methylation at single-base decision from picograms of DNA. Genome Res. 31, 1280–1289 (2021).

    PubMed Central 

    Google Scholar 

  • Picelli, S. et al. Full-length RNA-seq from single cells utilizing Sensible-seq2. Nat. Protoc. 9, 171–181 (2014).

    CAS 
    PubMed 

    Google Scholar 

  • Spencer, D. H. et al. CpG island hypermethylation mediated by DNMT3A is a consequence of AML development. Cell 168, 801–816 e13 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Glass, J. L. et al. Epigenetic id in AML is determined by disruption of nonpromoter regulatory parts and is affected by antagonistic results of mutations in epigenetic modifiers. Most cancers Discov. 7, 868–883 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Vaisvila, R. et al. Enzymatic methyl sequencing detects DNA methylation at single-base decision from picograms of DNA. Genome Res. 31, 1280–1289 (2021).

    PubMed Central 

    Google Scholar 

  • Wang, J. et al. Double restriction-enzyme digestion improves the protection and accuracy of genome-wide CpG methylation profiling by decreased illustration bisulfite sequencing. BMC Genomics 14, 11 (2013).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Andersson, R. et al. An atlas of lively enhancers throughout human cell sorts and tissues. Nature 507, 455–461 (2014).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Davis, C. A. et al. The encyclopedia of DNA parts (ENCODE): knowledge portal replace. Nucleic Acids Res. 46, D794–D801 (2018).

    CAS 
    PubMed 

    Google Scholar 

  • Adelman, E. R. et al. Ageing human hematopoietic stem cells manifest profound epigenetic reprogramming of enhancers that will predispose to leukemia. Most cancers Discov. 9, 1080–1101 (2019).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Jeong, M. et al. Massive conserved domains of low DNA methylation maintained by Dnmt3a. Nat. Genet. 46, 17–23 (2014).

    CAS 
    PubMed 

    Google Scholar 

  • Zhang, X. et al. Massive DNA methylation nadirs anchor chromatin loops sustaining hematopoietic stem cell id. Mol. Cell 78, 506–521 e6 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hawkins, R. D. et al. Distinct epigenomic landscapes of pluripotent and lineage-committed human cells. Cell Stem Cell 6, 479–491 (2010).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Margueron, R. & Reinberg, D. The Polycomb advanced PRC2 and its mark in life. Nature 469, 343–349 (2011).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Mohn, F. et al. Lineage-specific polycomb targets and de novo DNA methylation outline restriction and potential of neuronal progenitors. Mol. Cell 30, 755–766 (2008).

    CAS 
    PubMed 

    Google Scholar 

  • Xie, H. et al. Polycomb repressive advanced 2 regulates regular hematopoietic stem cell operate in a developmental-stage-specific method. Cell Stem Cell 14, 68–80 (2014).

    CAS 
    PubMed 

    Google Scholar 

  • Most cancers Genome Atlas Analysis Community. Genomic and epigenomic landscapes of grownup de novo acute myeloid leukemia. N. Engl. J. Med. 368, 2059–2074 (2013).

    Google Scholar 

  • Emperle, M. et al. Mutations of R882 change flanking sequence preferences of the DNA methyltransferase DNMT3A and mobile methylation patterns. Nucleic Acids Res. 47, 11355–11367 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Anteneh, H., Fang, J. & Tune, J. Structural foundation for impairment of DNA methylation by the DNMT3A R882H mutation. Nat. Commun. 11, 2294 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yin, Y. et al. Impression of cytosine methylation on DNA binding specificities of human transcription elements. Science 356, eaaj2239 (2017).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Prendergast, G. C. & Ziff, E. B. Methylation-sensitive sequence-specific DNA binding by the c-Myc fundamental area. Science 251, 186–189 (1991).

    CAS 
    PubMed 

    Google Scholar 

  • Tate, P. H. & Chook, A. P. Results of DNA methylation on DNA-binding proteins and gene expression. Curr. Opin. Genet Dev. 3, 226–231 (1993).

    CAS 
    PubMed 

    Google Scholar 

  • Grau, J., Schmidt, F. & Schulz, M.H. Widespread results of DNA methylation and intra-motif dependencies revealed by novel transcription issue binding fashions. Preprint at bioRxiv https://doi.org/10.1101/2020.10.21.348193 (2020).

  • Takubo, Okay. et al. Regulation of the HIF-1alpha degree is important for hematopoietic stem cells. Cell Stem Cell 7, 391–402 (2010).

    CAS 
    PubMed 

    Google Scholar 

  • Krock, B. L. et al. The aryl hydrocarbon receptor nuclear translocator is a necessary regulator of murine hematopoietic stem cell viability. Blood 125, 3263–3272 (2015).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Mariani, C. J. et al. TET1-mediated hydroxymethylation facilitates hypoxic gene induction in neuroblastoma. Cell Rep. 7, 1343–1352 (2014).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Li, Y. et al. Setd1a and NURF mediate chromatin dynamics and gene regulation throughout erythroid lineage dedication and differentiation. Nucleic Acids Res. 44, 7173–7188 (2016).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Huang, S., Li, X., Yusufzai, T. M., Qiu, Y. & Felsenfeld, G. USF1 recruits histone modification complexes and is crucial for upkeep of a chromatin barrier. Mol. Cell. Biol. 27, 7991–8002 (2007).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Arnaud, L. et al. A dominant mutation within the gene encoding the erythroid transcription issue KLF1 causes a congenital dyserythropoietic anemia. Am. J. Hum. Genet. 87, 721–727 (2010).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Grosselin, Okay. et al. Excessive-throughput single-cell ChIP-seq identifies heterogeneity of chromatin states in breast most cancers. Nat. Genet. 51, 1060–1066 (2019).

    CAS 
    PubMed 

    Google Scholar 

  • Rotem, A. et al. Single-cell ChIP-seq reveals cell subpopulations outlined by chromatin state. Nat. Biotechnol. 33, 1165–1172 (2015).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wang, Q. et al. CoBATCH for high-throughput single-cell epigenomic profiling. Mol. Cell 76, 206–216 e7 (2019).

    CAS 
    PubMed 

    Google Scholar 

  • Fu, L. et al. Predicting transcription issue binding in single cells via deep studying. Sci. Adv. 6, eaba9031 (2020).

    CAS 
    PubMed 

    Google Scholar 

  • Ugarte, F. et al. Progressive chromatin condensation and H3K9 methylation regulate the differentiation of embryonic and hematopoietic stem cells. Stem Cell Rep. 5, 728–740 (2015).

    CAS 

    Google Scholar 

  • Martin, E. W. et al. Chromatin accessibility maps present proof of multilineage gene priming in hematopoietic stem cells. Epigenetics Chromatin 14, 2 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Granja, J. M. et al. Single-cell multiomic evaluation identifies regulatory packages in mixed-phenotype acute leukemia. Nat. Biotechnol. 37, 1458–1465 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Setty, M. et al. Characterization of cell destiny chances in single-cell knowledge with Palantir. Nat. Biotechnol. 37, 451–460 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Stoeckius, M. et al. Simultaneous epitope and transcriptome measurement in single cells. Nat. Strategies 14, 865–868 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zavidij, O. et al. Single-cell RNA sequencing reveals compromised immune microenvironment in precursor levels of a number of myeloma. Nat. Most cancers 1, 493–506 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Izzo, F. et al. DNA methylation disruption reshapes the hematopoietic differentiation panorama. Nat. Genet. 52, 378–387 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lessard, J. & Sauvageau, G. Bmi-1 determines the proliferative capability of regular and leukaemic stem cells. Nature 423, 255–260 (2003).

    CAS 
    PubMed 

    Google Scholar 

  • Liu, Y. et al. Convergence of oncogenic cooperation at single-cell and single-gene ranges drives leukemic transformation. Nat. Commun. 12, 6323 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lu, R. et al. A mannequin system for finding out the DNMT3A hotspot mutation (DNMT3A(R882)) demonstrates a causal relationship between its dominant-negative impact and leukemogenesis. Most cancers Res. 79, 3583–3594 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • van Galen, P. et al. The unfolded protein response governs integrity of the haematopoietic stem-cell pool throughout stress. Nature 510, 268–272 (2014).

    PubMed 

    Google Scholar 

  • Rodriguez-Meira, A. et al. Unravelling intratumoral heterogeneity via high-sensitivity single-cell mutational evaluation and parallel RNA sequencing. Mol. Cell 73, 1292–1305 e8 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Petti, A. A. et al. A normal method for detecting expressed mutations in AML cells utilizing single cell RNA-sequencing. Nat. Commun. 10, 3660 (2019).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Ludwig, L. S. et al. Lineage tracing in people enabled by mitochondrial mutations and single-cell genomics. Cell 176, 1325–1339 e22 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Nam, A. S., Chaligne, R. & Landau, D. A. Integrating genetic and non-genetic determinants of most cancers evolution by single-cell multi-omics. Nat. Rev. Genet. 22, 3–18 (2021).

    CAS 
    PubMed 

    Google Scholar 

  • ENCODE Venture Consortium.An built-in encyclopedia of DNA parts within the human genome. Nature 489, 57–74 (2012).

    Google Scholar 

  • Saxonov, S., Berg, P. & Brutlag, D. L. A genome-wide evaluation of CpG dinucleotides within the human genome distinguishes two distinct lessons of promoters. Proc. Natl Acad. Sci. USA 103, 1412–1417 (2006).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Aibar, S. et al. SCENIC: single-cell regulatory community inference and clustering. Nat. Strategies 14, 1083–1086 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gothert, J. R. et al. In vivo fate-tracing research utilizing the Scl stem cell enhancer: embryonic hematopoietic stem cells considerably contribute to grownup hematopoiesis. Blood 105, 2724–2732 (2005).

    PubMed 

    Google Scholar 

  • Butler, A., Hoffman, P., Smibert, P., Papalexi, E. & Satija, R. Integrating single-cell transcriptomic knowledge throughout totally different situations, applied sciences, and species. Nat. Biotechnol. 36, 411–420 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Tange, O. GNU Parallel 20200622. Pc Program. Zenodo https://doi.org/10.5281/zenodo.3956817 (2020).

  • Yu, G., Wang, L.-G., Han, Y. & He, Q.-Y. clusterProfiler: an R package deal for evaluating organic themes amongst gene clusters. OMICS 16, 284–287 (2012).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Granja, J. M. et al. ArchR is a scalable software program package deal for integrative single-cell chromatin accessibility evaluation. Nat. Genet. 53, 403–411 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

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