中文版 | English


Alternative Title
Name pinyin
ZHANG Jingwen
School number
0710 生物学
Subject category of dissertation
07 理学
Mentor unit
Publication Years
Submission date
Place of Publication


这里我们建立了一种结合特殊条形码标记(Cell barcoding)谱系追踪策略和单细胞染色质可及性测序(scATAC-seq)的方法,可以用于绘制细胞命运决定过程中染色质可及性动态变化图谱。通过逆转录病毒将条形码标记整合到细胞基因组,以在细胞中拷贝数较高的条形码RNA作为遗传标记保证绝大多数的单细胞都能被克隆追踪。同时,基于流式分选的scATAC-seq能够产生具有高复杂性的ATAC文库。通过这种方法在单个细胞中生成配对的条形码信息和染色质可及性信息。最后,我们将这种方法应用于分析结直肠癌细胞对于低氧环境的不同应答,研究结直肠癌细胞在低氧处理前后染色质可及性的差异。此外,此方法还适用于基于液滴的高通量scATAC-seq测序,未来可以为更复杂的组织绘制命运决定的染色质可及性动态轨迹,具有巨大的应用潜力。


Other Abstract

How is the fate of cells determined? This is a vital question in the life sciences. Single cell omics technologies have provided a new insight to understand the underlying fate-determining signals of cells at the epigenetic and transcriptional level. Innovations combining lineage tracing and single-cell sequencing have helped revealing the heterogeneity of human cell populations, facilitated the mapping of clonal relationships between ancestors and progeny. Here, we establish a method that integrates lineage tracing and single-cell assay for transposase-accessible chromatin with sequencing (scATAC-seq) to map chromatin dynamics during cell fate determination. In this method, we performed in-situ reverse transcription & ATAC-seq to generate paired genetics barcode information and chromatin landscape in single cells. To do so, genetic barcode was designed and integrated into the genome via lentivirus. In-situ reverse transcription was used to capture barcode RNAs that to improve the efficiency of cellular barcoding. “Tagmentation” of chromatin were then performed to single cells or nuclei, which were isolated with flow cytometry. Afterwards, multi-complexity scATAC library with genetic barcoding was generated. Using this method, we will analyze accessible chromatin states of colorectal cells that produce different fate decision under hypoxia. Furthermore, our approach could also be adapted to high-throughput droplet-based single-cell sequencing platform to tackle the complexity of tissues.

Training classes
Enrollment Year
Year of Degree Awarded
References List

[1] WATT F M, JENSEN K B. Epidermal stem cell diversity and quiescence[J]. EMBO Mol Med, 2009, 1(5): 260-267.
[2] KASPER M, JAKS V, ARE A, et al. Wounding enhances epidermal tumorigenesis by recruiting hair follicle keratinocytes[J]. Proc Natl Acad Sci U S A, 2011, 108(10): 4099-4104.
[3] WEINREB C, RODRIGUEZ-FRATICELLI A, CAMARGO F D, et al. Lineage tracing on transcriptional landscapes links state to fate during differentiation[J]. Science, 2020, 367(6479)
[4] CONKLIN E G. Mosaic development in ascidian eggs[J]. Journal of Experimental Zoology, 1905, 2(2): 145-223.
[5] SPEMANN H, MANGOLD H. The induction of embryonic predispositions by implantation of organizers foreign to the species.[J]. Archiv Fur Mikroskopische Anatomie Und Entwicklungsmechanik, 1924, 100(3/4): 599-638.
[6] SERBEDZIJA G N, BRONNER-FRASER M, FRASER S E. A vital dye analysis of the timing and pathways of avian trunk neural crest cell migration[J]. Development, 1989, 106(4): 809-816.
[7] EAGLESON G W, HARRIS W A. Mapping of the presumptive brain regions in the neural plate of Xenopus laevis[J]. J Neurobiol, 1990, 21(3): 427-440.
[8] WEISBLAT D A, SAWYER R T, STENT G S. Cell lineage analysis by intracellular injection of a tracer enzyme[J]. Science, 1978, 202(4374): 1295-1298.
[9] BALAKIER H, PEDERSEN R A. Allocation of cells to inner cell mass and trophectoderm lineages in preimplantation mouse embryos[J]. Dev Biol, 1982, 90(2): 352-362.
[10] CHALFIE M, TU Y, EUSKIRCHEN G, et al. Green Fluorescent Protein as a Marker for Gene-Expression[J]. Science, 1994, 263(5148): 802-805.
[11] HOLT C E, GARLICK N, CORNEL E. Lipofection of cDNAs in the embryonic vertebrate central nervous system[J]. Neuron, 1990, 4(2): 203-214.
[12] LEMISCHKA I R, RAULET D H, MULLIGAN R C. Developmental potential and dynamic behavior of hematopoietic stem cells[J]. Cell, 1986, 45(6): 917-927.
[13] KRETZSCHMAR K, WATT F M. Lineage tracing[J]. Cell, 2012, 148(1-2): 33-45.
[14] HARRISON D A, PERRIMON N. Simple and efficient generation of marked clones in Drosophila[J]. Curr Biol, 1993, 3(7): 424-433.
[15] OHLSTEIN B, SPRADLING A. The adult Drosophila posterior midgut is maintained by pluripotent stem cells[J]. Nature, 2006, 439(7075): 470-474.
[16] FRUMKIN D, WASSERSTROM A, KAPLAN S, et al. Genomic variability within an organism exposes its cell lineage tree[J]. Plos Computational Biology, 2005, 1(5): 382-394.
[17] SALIPANTE S J, HORWITZ M S. Phylogenetic fate mapping[J]. Proceedings of the National Academy of Sciences of the United States of America, 2006, 103(14): 5448-5453.
[18] CARLSON C A, KAS A, KIRKWOOD R, et al. Decoding cell lineage from acquired mutations using arbitrary deep sequencing[J]. Nature Methods, 2012, 9(1): 78-U193.
[19] BEHJATI S, HUCH M, VAN BOXTEL R, et al. Genome sequencing of normal cells reveals developmental lineages and mutational processes[J]. Nature, 2014, 513(7518): 422-425.
[20] BIDDY B A, KONG W J, KAMIMOTO K, et al. Single-cell mapping of lineage and identity in direct reprogramming[J]. Nature, 2018, 564(7735): 219-224.
[21] WOODWORTH M B, GIRSKIS K M, WALSH C A. Building a lineage from single cells: genetic techniques for cell lineage tracking[J]. Nature Reviews Genetics, 2017, 18(4): 230-244.
[22] PEIKON I D, GIZATULLINA D I, ZADOR A M. In vivo generation of DNA sequence diversity for cellular barcoding[J]. Nucleic Acids Research, 2014, 42(16).
[23] MCKENNA A, FINDLAY G M, GAGNON J A, et al. Whole-organism lineage tracing by combinatorial and cumulative genome editing[J]. Science, 2016, 353(6298): aaf7907.
[24] FRIEDA K L, LINTON J M, HORMOZ S, et al. Synthetic recording and in situ readout of lineage information in single cells[J]. Nature, 2017, 541(7635): 107-111.
[25] PEI W, FEYERABEND T B, ROSSLER J, et al. Polylox barcoding reveals haematopoietic stem cell fates realized in vivo[J]. Nature, 2017, 548(7668): 456-460.
[26] SPANJAARD B, HU B, MITIC N, et al. Simultaneous lineage tracing and cell-type identification using CRISPR-Cas9-induced genetic scars[J]. Nat Biotechnol, 2018, 36(5): 469-473.
[27] ALLEN F, CREPALDI L, ALSINET C, et al. Predicting the mutations generated by repair of Cas9-induced double-strand breaks[J]. Nat Biotechnol, 2018, 37: 64-72.
[28] CHEN W, MCKENNA A, SCHREIBER J, et al. Massively parallel profiling and predictive modeling of the outcomes of CRISPR/Cas9-mediated double-strand break repair[J]. Nucleic Acids Research, 2019, 47(15): 7989-8003.
[29] MCKENNA A, GAGNON J A. Recording development with single cell dynamic lineage tracing[J]. Development, 2019, 146(12): dev169730.
[30] KLEMM S L, SHIPONY Z, GREENLEAF W J. Chromatin accessibility and the regulatory epigenome[J]. Nat Rev Genet, 2019, 20(4): 207-220.
[31] BOSTOCK C J, CHRISTIE S, HATCH F T. Accessibility of DNA in condensed chromatin to nuclease digestion[J]. Nature, 1976, 262(5568): 516-519.
[32] KAPLAN N, MOORE I K, FONDUFE-MITTENDORF Y, et al. The DNA-encoded nucleosome organization of a eukaryotic genome[J]. Nature, 2009, 458(7236): 362-366.
[33] LORCH Y, LAPOINTE J W, KORNBERG R D. Nucleosomes inhibit the initiation of transcription but allow chain elongation with the displacement of histones[J]. Cell, 1987, 49(2): 203-210.
[34] LUGER K, MADER A W, RICHMOND R K, et al. Crystal structure of the nucleosome core particle at 2.8 A resolution[J]. Nature, 1997, 389(6648): 251-260.
[35] OLINS A L, OLINS D E. Spheroid chromatin units (v bodies)[J]. Science, 1974, 183(4122): 330-332.
[36] WOODCOCK C L, SAFER J P, STANCHFIELD J E. Structural repeating units in chromatin. I. Evidence for their general occurrence[J]. Exp Cell Res, 1976, 97: 101-110.
[37] KORNBERG R D, THOMAS J O. Chromatin structure; oligomers of the histones[J]. Science, 1974, 184(4139): 865-868.
[38] DANN G P, LISZCZAK G P, BAGERT J D, et al. ISWI chromatin remodellers sense nucleosome modifications to determine substrate preference[J]. Nature, 2017, 548(7669): 607-611.
[39] ALLIS C D, JENUWEIN T. The molecular hallmarks of epigenetic control[J]. Nat Rev Genet, 2016, 17(8): 487-500.
[40] MCBRYANT S J, ADAMS V H, HANSEN J C. Chromatin architectural proteins[J]. Chromosome Res, 2006, 14(1): 39-51.
[41] BEDNAR J, HOROWITZ R A, GRIGORYEV S A, et al. Nucleosomes, linker DNA, and linker histone form a unique structural motif that directs the higher-order folding and compaction of chromatin[J]. Proc Natl Acad Sci U S A, 1998, 95(24): 14173-14178.
[42] FYODOROV D V, ZHOU B R, SKOULTCHI A I, et al. Emerging roles of linker histones in regulating chromatin structure and function[J]. Nat Rev Mol Cell Biol, 2018, 19(3): 192-206.
[43] ROUTH A, SANDIN S, RHODES D. Nucleosome repeat length and linker histone stoichiometry determine chromatin fiber structure[J]. Proc Natl Acad Sci U S A, 2008, 105(26): 8872-8877.
[44] LEE C K, SHIBATA Y, RAO B, et al. Evidence for nucleosome depletion at active regulatory regions genome-wide[J]. Nature Genetics, 2004, 36(8): 900-905.
[45] THURMAN R E, RYNES E, HUMBERT R, et al. The accessible chromatin landscape of the human genome[J]. Nature, 2012, 489(7414): 75-82.
[46] POIRIER M G, BUSSIEK M, LANGOWSKI J, et al. Spontaneous access to DNA target sites in folded chromatin fibers[J]. J Mol Biol, 2008, 379(4): 772-786.
[47] THURMAN R E, RYNES E, HUMBERT R, et al. The accessible chromatin landscape of the human genome[J]. Nature, 2012, 489(7414): 75-82.
[48] KREBS A R, IMANCI D, HOERNER L, et al. Genome-wide Single-Molecule Footprinting Reveals High RNA Polymerase II Turnover at Paused Promoters[J]. Mol Cell, 2017, 67(3): 411-422 e414.
[49] FEDOR M J. Chromatin structure and gene expression[J]. Curr Opin Cell Biol, 1992, 4(3): 436-443.
[50] JOHN S, SABO P J, THURMAN R E, et al. Chromatin accessibility pre-determines glucocorticoid receptor binding patterns[J]. Nat Genet, 2011, 43(3): 264-268.
[51] DI STEFANO B, COLLOMBET S, JAKOBSEN J S, et al. C/EBPalpha creates elite cells for iPSC reprogramming by upregulating Klf4 and increasing the levels of Lsd1 and Brd4[J]. Nat Cell Biol, 2016, 18(4): 371-381.
[52] BAROZZI I, SIMONATTO M, BONIFACIO S, et al. Coregulation of transcription factor binding and nucleosome occupancy through DNA features of mammalian enhancers[J]. Mol Cell, 2014, 54(5): 844-857.
[53] GRONTVED L, JOHN S, BAEK S, et al. C/EBP maintains chromatin accessibility in liver and facilitates glucocorticoid receptor recruitment to steroid response elements[J]. EMBO J, 2013, 32(11): 1568-1583.
[54] BUENROSTRO J D, GIRESI P G, ZABA L C, et al. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position[J]. Nature Methods, 2013, 10(12): 1213-1218.
[55] HEWISH D R, BURGOYNE L A. Chromatin sub-structure. The digestion of chromatin DNA at regularly spaced sites by a nuclear deoxyribonuclease[J]. Biochem Biophys Res Commun, 1973, 52(2): 504-510.
[56] WU C, BINGHAM P M, LIVAK K J, et al. The chromatin structure of specific genes: I. Evidence for higher order domains of defined DNA sequence[J]. Cell, 1979, 16(4): 797-806.
[57] KORNBERG R D. Chromatin structure: a repeating unit of histones and DNA[J]. Science, 1974, 184(4139): 868-871.
[58] SAIKI R K, SCHARF S, FALOONA F, et al. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia[J]. Science, 1985, 230(4732): 1350-1354.
[59] JOHN S, SABO P J, JOHNSON T A, et al. Interaction of the glucocorticoid receptor with the chromatin landscape[J]. Mol Cell, 2008, 29(5): 611-624.
[60] CRAWFORD G E, DAVIS S, SCACHERI P C, et al. DNase-chip: a high-resolution method to identify DNase I hypersensitive sites using tiled microarrays[J]. Nature Methods, 2006, 3(7): 503-509.
[61] SABO P J, KUEHN M S, THURMAN R, et al. Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays[J]. Nature Methods, 2006, 3(7): 511-518.
[62] BOYLE A P, DAVIS S, SHULHA H P, et al. High-resolution mapping and characterization of open chromatin across the genome[J]. Cell, 2008, 132(2): 311-322.
[63] HESSELBERTH J R, CHEN X, ZHANG Z, et al. Global mapping of protein-DNA interactions in vivo by digital genomic footprinting[J]. Nature Methods, 2009, 6(4): 283-289.
[64] MIECZKOWSKI J, COOK A, BOWMAN S K, et al. MNase titration reveals differences between nucleosome occupancy and chromatin accessibility[J]. Nature Communications, 2016, 7(11485).
[65] MUELLER B, MIECZKOWSKI J, KUNDU S, et al. Widespread changes in nucleosome accessibility without changes in nucleosome occupancy during a rapid transcriptional induction[J]. Genes & Development, 2017, 31(5): 451-462.
[66] ALLAN J, FRASER R M, OWEN-HUGHES T, et al. Micrococcal nuclease does not substantially bias nucleosome mapping[J]. J Mol Biol, 2012, 417(3): 152-164.
[67] CHUNG H R, DUNKEL I, HEISE F, et al. The Effect of Micrococcal Nuclease Digestion on Nucleosome Positioning Data[J]. PLoS One, 2010, 5(12): e15754.
[68] KREBS A R, IMANCI D, HOERNER L, et al. Genome-wide Single-Molecule Footprinting Reveals High RNA Polymerase II Turnover at Paused Promoters[J]. Molecular Cell, 2017, 67(3): 411-422.e4.
[69] KELLY T K, LIU Y P, LAY F D, et al. Genome-wide mapping of nucleosome positioning and DNA methylation within individual DNA molecules[J]. Genome Research, 2012, 22(12): 2497-2506.
[70] CORCES M R, TREVINO A E, HAMILTON E G, et al. An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues[J]. Nature Methods, 2017, 14(10): 959-962.
[71] HE H H, MEYER C A, HU S S, et al. Refined DNase-seq protocol and data analysis reveals intrinsic bias in transcription factor footprint identification[J]. Nature Methods, 2014, 11(1): 73-78.
[72] SCHEP A N, BUENROSTRO J D, DENNY S K, et al. Structured nucleosome fingerprints enable high-resolution mapping of chromatin architecture within regulatory regions[J]. Genome Res, 2015, 25(11): 1757-1770.
[73] BUENROSTRO J D, WU B, CHANG H Y, et al. ATAC-seq: A Method for Assaying Chromatin Accessibility Genome-Wide[J]. Curr Protoc Mol Biol, 2015, 109: 21-29.
[74] BUENROSTRO J D, WU B, LITZENBURGER U M, et al. Single-cell chromatin accessibility reveals principles of regulatory variation[J]. Nature, 2015, 523(7561): 486-490.
[75] CUSANOVICH D A, HILL A J, AGHAMIRZAIE D, et al. A Single-Cell Atlas of In Vivo Mammalian Chromatin Accessibility[J]. Cell, 2018, 174(5): 1309-1324 e1318.
[76] MEZGER A, KLEMM S, MANN I, et al. High-throughput chromatin accessibility profiling at single-cell resolution[J]. Nature Communications, 2018, 9(3647).
[77] CORCES M R, BUENROSTRO J D, WU B J, et al. Lineage-specific and single-cell chromatin accessibility charts human hematopoiesis and leukemia evolution[J]. Nature Genetics, 2016, 48(10): 1193-1203.
[78] BUENOSTRO J D, WU B J, LITZENBURGER U M, et al. Single-cell chromatin accessibility reveals principles of regulatory variation[J]. Nature, 2015, 523(7561): 486-U264.
[79] CUSANOVICH D A, DAZA R, ADEY A, et al. Multiplex single-cell profiling of chromatin accessibility by combinatorial cellular indexing[J]. Science, 2015, 348(6237): 910-914.
[80] GRUN D, VAN OUDENAARDEN A. Design and Analysis of Single-Cell Sequencing Experiments[J]. Cell, 2015, 163(4): 799-810.
[81] HABER A L, BITON M, ROGEL N, et al. A single-cell survey of the small intestinal epithelium[J]. Nature, 2017, 551(7680): 333-339.
[82] KLEIN A M, MAZUTIS L, AKARTUNA I, et al. Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells[J]. Cell, 2015, 161(5): 1187-1201.
[83] PURAM S V, TIROSH I, PARIKH A S, et al. Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer[J]. Cell, 2017, 171(7): 1611-1624 e1624.
[84] CANNOODT R, SAELENS W, SAEYS Y. Computational methods for trajectory inference from single-cell transcriptomics[J]. Eur J Immunol, 2016, 46(11): 2496-2506.
[85] ALEMANY A, FLORESCU M, BARON C S, et al. Whole-organism clone tracing using single-cell sequencing[J]. Nature, 2018, 556(7699): 108-112.
[86] RAJ B, WAGNER D E, MCKENNA A, et al. Simultaneous single-cell profiling of lineages and cell types in the vertebrate brain[J]. Nat Biotechnol, 2018, 36(5): 442-450.
[87] KESTER L, VAN OUDENAARDEN A. Single-Cell Transcriptomics Meets Lineage Tracing[J]. Cell Stem Cell, 2018, 23(2): 166-179.
[88] JAITIN D A, KENIGSBERG E, KEREN-SHAUL H, et al. Massively parallel single-cell RNA-seq for marker-free decomposition of tissues into cell types[J]. Science, 2014, 343(6172): 776-779.
[89] PAUL F, ARKIN Y, GILADI A, et al. Transcriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors[J]. Cell, 2015, 163(7): 1663-1677.
[90] RODRIGUEZ-FRATICELLI A E, WOLOCK S L, WEINREB C S, et al. Clonal analysis of lineage fate in native haematopoiesis[J]. Nature, 2018, 553(7687): 212-216.
[91] CARRELHA J, MENG Y, KETTYLE L M, et al. Hierarchically related lineage-restricted fates of multipotent haematopoietic stem cells[J]. Nature, 2018, 554(7690): 106-111.
[92] GILADI A, AMIT I. Single-Cell Genomics: A Stepping Stone for Future Immunology Discoveries[J]. Cell, 2018, 172(1-2): 14-21.
[93] DOMCKE S, HILL A J, DAZA R M, et al. A human cell atlas of fetal chromatin accessibility[J]. Science, 2020, 370(6518): 7612-7721.
[94] CAO J Y, CUSANOVICH D A, RAMANI V, et al. Joint profiling of chromatin accessibility and gene expression in thousands of single cells[J]. Science, 2018, 361(6409): 1380-1385.
[95] MCKENNA A, FINDLAY G M, GAGNON J A, et al. Whole-organism lineage tracing by combinatorial and cumulative genome editing[J]. Science, 2016, 353(6298).
[96] LUDWIG L S, LAREAU C A, ULIRSCH J C, et al. Lineage Tracing in Humans Enabled by Mitochondrial Mutations and Single-Cell Genomics[J]. Cell, 2019, 176(6): 1325-1339 e1322.
[97] CHEN X, MIRAGAIA R J, NATARAJAN K N, et al. A rapid and robust method for single cell chromatin accessibility profiling[J]. Nat Commun, 2018, 9(1): 5345.
[98] BLATTMAN S B, JIANG W, OIKONOMOU P, et al. Prokaryotic single-cell RNA sequencing by in situ combinatorial indexing[J]. Nat Microbiol, 2020, 5(10): 1192-1201.
[99] ATTAR M, SHARMA E, LI S, et al. A practical solution for preserving single cells for RNA sequencing[J]. Sci Rep, 2018, 8(1): 2151.
[100] CAO J, PACKER J S, RAMANI V, et al. Comprehensive single-cell transcriptional profiling of a multicellular organism[J]. Science, 2017, 357(6352): 661-667.
[101] CHEN J, CHEUNG F, SHI R, et al. PBMC fixation and processing for Chromium single-cell RNA sequencing[J]. J Transl Med, 2018, 16(1): 198.
[102] HOBRO A J, SMITH N I. An evaluation of fixation methods: Spatial and compositional cellular changes observed by Raman imaging[J]. Vibrational Spectroscopy, 2017, 91: 31-45.
[103] ALLES J, KARAISKOS N, PRAKTIKNJO S D, et al. Cell fixation and preservation for droplet-based single-cell transcriptomics[J]. Bmc Biology, 2017, 15(44).
[104] SUMNER A T, EVANS H J, BUCKLAND R A. Mechanisms Involved in Banding of Chromosomes with Quinacrine and Giemsa .1. Effects of Fixation in Methanol-Acetic Acid[J]. Experimental Cell Research, 1973, 81(1): 214-222.
[105] XIANG C C, MEZEY E, CHEN M, et al. Using DSP, a reversible cross-linker, to fix tissue sections for immunostaining, microdissection and expression profiling[J]. Nucleic Acids Research, 2004, 32(22): e185.
[106] CUSANOVICH D A, HILL A J, AGHAMIRZAIE D, et al. A Single-Cell Atlas of In Vivo Mammalian Chromatin Accessibility[J]. Cell, 2018, 174(5): 1309.
[107] PLINER H A, PACKER J S, MCFALINE-FIGUEROA J L, et al. Cicero Predicts cis-Regulatory DNA Interactions from Single-Cell Chromatin Accessibility Data[J]. Molecular Cell, 2018, 71(5): 858.
[108] BUENROSTRO J D, CORCES M R, LAREAU C A, et al. Integrated Single-Cell Analysis Maps the Continuous Regulatory Landscape of Human Hematopoietic Differentiation[J]. Cell, 2018, 173(6): 1535-1548 e1516.
[109] LAREAU C A, LUDWIG L S, MUUS C, et al. Massively parallel single-cell mitochondrial DNA genotyping and chromatin profiling[J]. Nat Biotechnol, 2021, 39(4): 451-461.
[110] XU J, NUNO K, LITZENBURGER U M, et al. Single-cell lineage tracing by endogenous mutations enriched in transposase accessible mitochondrial DNA[J]. Elife, 2019, 8: e45105.
[111] MA S, ZHANG B, LAFAVE L M, et al. Chromatin Potential Identified by Shared Single-Cell Profiling of RNA and Chromatin[J]. Cell, 2020, 183(4): 1103-1116 e1120.
[112] BIDDY B A, KONG W, KAMIMOTO K, et al. Single-cell mapping of lineage and identity in direct reprogramming[J]. Nature, 2018, 564(7735): 219-224.
[113] ALEMANY A, FLORESCU M, BARON C S, et al. Whole-organism clone tracing using single-cell sequencing[J]. Nature, 2018, 556(7699): 108.
[114] MUTO Y, WILSON P C, LEDRU N, et al. Single cell transcriptional and chromatin accessibility profiling redefine cellular heterogeneity in the adult human kidney[J]. Nat Commun, 2021, 12(1): 2190.
[115] TREVINO A E, MULLER F, ANDERSEN J, et al. Chromatin and gene-regulatory dynamics of the developing human cerebral cortex at single-cell resolution[J]. Cell, 2021, 184(19): 5053-5069 e5023.
[116] MA S, ZHANG B, LAFAVE L M, et al. Chromatin Potential Identified by Shared Single-Cell Profiling of RNA and Chromatin[J]. Cell, 2020, 183(4): 1103.
[117] SEMENZA G L. Oxygen Sensing, Hypoxia-Inducible Factors, and Disease Pathophysiology[J]. Annual Review of Pathology: Mechanisms of Disease, Vol 9, 2014, 9: 47-71.
[118] SEMENZA G L. Oxygen sensing, hypoxia-inducible factors, and disease pathophysiology[J]. Annu Rev Pathol, 2014, 9: 47-71.
[119] BENITA Y, KIKUCHI H, SMITH A D, et al. An integrative genomics approach identifies Hypoxia Inducible Factor-1 (HIF-1)-target genes that form the core response to hypoxia[J]. Nucleic Acids Research, 2009, 37(14): 4587-4602.
[120] ANDRYSIK Z, BENDER H, GALBRAITH M D, et al. Multi-omics analysis reveals contextual tumor suppressive and oncogenic gene modules within the acute hypoxic response[J]. Nature Communications, 2021, 12(1375).
[121] HIRAGA T, KIZAKA-KONDOH S, HIROTA K, et al. Hypoxia and hypoxia-inducible factor-1 expression enhance osteolytic bone metastases of breast cancer[J]. Cancer Research, 2007, 67(9): 4157-4163.
[122] SEMENZA G L. Regulation of Oxygen Homeostasis by Hypoxia-Inducible Factor 1[J]. Physiology, 2009, 24(2): 97-106.
[123] HARRIS A L. Hypoxia - A key regulatory factor in tumour growth[J]. Nature Reviews Cancer, 2002, 2(1): 38-47.
[124] PUNT C J A, KOOPMAN M, VERMEULEN L. From tumour heterogeneity to advances in precision treatment of colorectal cancer[J]. Nature Reviews Clinical Oncology, 2017, 14(4): 235-246.
[125] SADANANDAM A, LYSSIOTIS C A, HOMICSKO K, et al. A colorectal cancer classification system that associates cellular phenotype and responses to therapy[J]. Nature Medicine, 2013, 19(5): 619-625.
[126] BIAN S H, HOU Y, ZHOU X, et al. Single-cell multiomics sequencing and analyses of human colorectal cancer[J]. Science, 2018, 362(6418): 1060.

Academic Degree Assessment Sub committee
Domestic book classification number
Data Source
Document TypeThesis
DepartmentDepartment of Biology
Recommended Citation
GB/T 7714
张靖雯. 结合谱系追踪和单细胞染色质可及性的细胞命运决定研究[D]. 深圳. 南方科技大学,2022.
Files in This Item:
File Name/Size DocType Version Access License
11930131-张靖雯-生物系.pdf(12379KB) Restricted Access--Fulltext Requests
Related Services
Recommend this item
Usage statistics
Export to Endnote
Export to Excel
Export to Csv
Altmetrics Score
Google Scholar
Similar articles in Google Scholar
[张靖雯]'s Articles
Baidu Scholar
Similar articles in Baidu Scholar
[张靖雯]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[张靖雯]'s Articles
Terms of Use
No data!
Social Bookmark/Share
No comment.

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.