Recent Developments and Applications of Single-Cell RNA Sequencing Technology in Cell Classification

Safir Ullah Khan*; Munir Ullah Khan

**Safir Ullah Khan* and Munir Ullah Khan**

Volume2-Issue12
Dates: Received: 2021-12-07 | Accepted: 2021-12-27 | Published: 2021-12-29
Pages: 1283-1290

Abstract

Multicellular organisms have many cell types and are complex, and heterogeneity is common among cells. Single-Cell RNA Sequencing (scRNA-SEQ) is a new technique for studying the transcriptional activity of a single cell that is still in its early stages of development. It generates transcriptional profiles from thousands of parallel cells to reveal the differential expression of individual cell genomes. They reflect the heterogeneity between cells to identify different cell types and form cell maps of tissues or organs, which play an essential role in biology and clinical medicine. Based on the introduction and comparison of the scRNA-SEQ sequencing platform, this paper focuses on the application of scRNA-SEQ in the exploration of cell types in the nervous system and immune system and summarizes the research results of the combination of scRNA-SEQ and spatial transcriptome technology.

FullText HTML FullText PDF DOI: 10.37871/jbres1383

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How to cite this article

Khan SU, Khan MU. Recent Developments and Applications of Single-Cell RNA Sequencing Technology in Cell Classification. J Biomed Res Environ Sci. 2021 Dec 29; 2(12): 1283-1290. doi: 10.37871/jbres1383, Article ID: JBRES1383, Available at: https://www.jelsciences.com/articles/jbres1383.pdf

Subject area(s)

Molecular Biology

Genomics

Biology

University/Institute

University of Science and Technology of China

References

Tang F, Barbacioru C, Wang Y, Nordman E, Lee C, Xu N, Wang X, Bodeau J, Tuch BB, Siddiqui A, Lao K, Surani MA. mRNA-Seq whole-transcriptome analysis of a single cell. Nat Methods. 2009 May;6(5):377-82. doi: 10.1038/nmeth.1315. Epub 2009 Apr 6. PMID: 19349980.
Gross A, Schoendube J, Zimmermann S, Steeb M, Zengerle R, Koltay P. Technologies for Single-Cell Isolation. Int J Mol Sci. 2015 Jul 24;16(8):16897-919. doi: 10.3390/ijms160816897. PMID: 26213926; PMCID: PMC4581176.
Wagner M, Yoshihara M, Douagi I, Damdimopoulos A, Panula S, Petropoulos S, Lu H, Pettersson K, Palm K, Katayama S, Hovatta O, Kere J, Lanner F, Damdimopoulou P. Single-cell analysis of human ovarian cortex identifies distinct cell populations but no oogonial stem cells. Nat Commun. 2020 Mar 2;11(1):1147. doi: 10.1038/s41467-020-14936-3. PMID: 32123174; PMCID: PMC7052271.
Lange C, Rost F, Machate A, Reinhardt S, Lesche M, Weber A, Kuscha V, Dahl A, Rulands S, Brand M. Single cell sequencing of radial glia progeny reveals the diversity of newborn neurons in the adult zebrafish brain. Development. 2020 Jan 9;147(1):dev185595. doi: 10.1242/dev.185595. PMID: 31908317; PMCID: PMC6983714.
Kim DW, Yao Z, Graybuck LT, Kim TK, Nguyen TN, Smith KA, Fong O, Yi L, Koulena N, Pierson N, Shah S, Lo L, Pool AH, Oka Y, Pachter L, Cai L, Tasic B, Zeng H, Anderson DJ. Multimodal Analysis of Cell Types in a Hypothalamic Node Controlling Social Behavior. Cell. 2019 Oct 17;179(3):713-728.e17. doi: 10.1016/j.cell.2019.09.020. PMID: 31626771; PMCID: PMC7534821.
Hu P, Zhang W, Xin H, Deng G. Single Cell Isolation and Analysis. Front Cell Dev Biol. 2016 Oct 25;4:116. doi: 10.3389/fcell.2016.00116. PMID: 27826548; PMCID: PMC5078503.
Kim S, De Jonghe J, Kulesa AB, Feldman D, Vatanen T, Bhattacharyya RP, Berdy B, Gomez J, Nolan J, Epstein S, Blainey PC. High-throughput automated microfluidic sample preparation for accurate microbial genomics. Nat Commun. 2017 Jan 27;8:13919. doi: 10.1038/ncomms13919. PMID: 28128213; PMCID: PMC5290157.
Rzhevskiy AS, Razavi Bazaz S, Ding L, Kapitannikova A, Sayyadi N, Campbell D, Walsh B, Gillatt D, Ebrahimi Warkiani M, Zvyagin AV. Rapid and Label-Free Isolation of Tumour Cells from the Urine of Patients with Localised Prostate Cancer Using Inertial Microfluidics. Cancers (Basel). 2019 Dec 29;12(1):81. doi: 10.3390/cancers12010081. PMID: 31905736; PMCID: PMC7016827.
Streets AM, Zhang X, Cao C, Pang Y, Wu X, Xiong L, Yang L, Fu Y, Zhao L, Tang F, Huang Y. Microfluidic single-cell whole-transcriptome sequencing. Proc Natl Acad Sci U S A. 2014 May 13;111(19):7048-53. doi: 10.1073/pnas.1402030111. Epub 2014 Apr 29. PMID: 24782542; PMCID: PMC4024894.
Macosko EZ, Basu A, Satija R, Nemesh J, Shekhar K, Goldman M, Tirosh I, Bialas AR, Kamitaki N, Martersteck EM, Trombetta JJ, Weitz DA, Sanes JR, Shalek AK, Regev A, McCarroll SA. Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets. Cell. 2015 May 21;161(5):1202-1214. doi: 10.1016/j.cell.2015.05.002. PMID: 26000488; PMCID: PMC4481139.
Valihrach L, Androvic P, Kubista M. Platforms for Single-Cell Collection and Analysis. Int J Mol Sci. 2018 Mar 11;19(3):807. doi: 10.3390/ijms19030807. PMID: 29534489; PMCID: PMC5877668.
Wu AR, Neff NF, Kalisky T, Dalerba P, Treutlein B, Rothenberg ME, Mburu FM, Mantalas GL, Sim S, Clarke MF, Quake SR. Quantitative assessment of single-cell RNA-sequencing methods. Nat Methods. 2014 Jan;11(1):41-6. doi: 10.1038/nmeth.2694. Epub 2013 Oct 20. PMID: 24141493; PMCID: PMC4022966.
Hashimshony T, Senderovich N, Avital G, Klochendler A, de Leeuw Y, Anavy L, Gennert D, Li S, Livak KJ, Rozenblatt-Rosen O, Dor Y, Regev A, Yanai I. CEL-Seq2: sensitive highly-multiplexed single-cell RNA-Seq. Genome Biol. 2016 Apr 28;17:77. doi: 10.1186/s13059-016-0938-8. PMID: 27121950; PMCID: PMC4848782.
Jaitin DA, Kenigsberg E, Keren-Shaul H, Elefant N, Paul F, Zaretsky I, Mildner A, Cohen N, Jung S, Tanay A, Amit I. Massively parallel single-cell RNA-seq for marker-free decomposition of tissues into cell types. Science. 2014 Feb 14;343(6172):776-9. doi: 10.1126/science.1247651. PMID: 24531970; PMCID: PMC4412462.
M PN, Liu H, Bousounis P, Spurr L, Alomran N, Ibeawuchi H, Sein J, Reece-Stremtan D, Horvath A. Estimating the Allele-Specific Expression of SNVs From 10× Genomics Single-Cell RNA-Sequencing Data. Genes (Basel). 2020 Feb 25;11(3):240. doi: 10.3390/genes11030240. PMID: 32106453; PMCID: PMC7140866.
Vardi O, Shamir I, Javasky E, Goren A, Simon I. Biases in the SMART-DNA library preparation method associated with genomic poly dA/dT sequences. PLoS One. 2017 Feb 24;12(2):e0172769. doi: 10.1371/journal.pone.0172769. PMID: 28235101; PMCID: PMC5325289.
Walzer KA, Fradin H, Emerson LY, Corcoran DL, Chi JT. Latent transcriptional variations of individual Plasmodium falciparum uncovered by single-cell RNA-seq and fluorescence imaging. PLoS Genet. 2019 Dec 19;15(12):e1008506. doi: 10.1371/journal.pgen.1008506. PMID: 31856180; PMCID: PMC6952112.
Hashimshony T, Wagner F, Sher N, Yanai I. CEL-Seq: single-cell RNA-Seq by multiplexed linear amplification. Cell Rep. 2012 Sep 27;2(3):666-73. doi: 10.1016/j.celrep.2012.08.003. Epub 2012 Aug 30. PMID: 22939981.
Durante MA, Rodriguez DA, Kurtenbach S, Kuznetsov JN, Sanchez MI, Decatur CL, Snyder H, Feun LG, Livingstone AS, Harbour JW. Single-cell analysis reveals new evolutionary complexity in uveal melanoma. Nat Commun. 2020 Jan 24;11(1):496. doi: 10.1038/s41467-019-14256-1. PMID: 31980621; PMCID: PMC6981133.
Sridhar A, Hoshino A, Finkbeiner CR, Chitsazan A, Dai L, Haugan AK, Eschenbacher KM, Jackson DL, Trapnell C, Bermingham-McDonogh O, Glass I, Reh TA. Single-Cell Transcriptomic Comparison of Human Fetal Retina, hPSC-Derived Retinal Organoids, and Long-Term Retinal Cultures. Cell Rep. 2020 Feb 4;30(5):1644-1659.e4. doi: 10.1016/j.celrep.2020.01.007. PMID: 32023475; PMCID: PMC7901645.
Ziegenhain C, Vieth B, Parekh S, Reinius B, Guillaumet-Adkins A, Smets M, Leonhardt H, Heyn H, Hellmann I, Enard W. Comparative Analysis of Single-Cell RNA Sequencing Methods. Mol Cell. 2017 Feb 16;65(4):631-643.e4. doi: 10.1016/j.molcel.2017.01.023. PMID: 28212749.
Zhang X, Li T, Liu F, Chen Y, Yao J, Li Z, Huang Y, Wang J. Comparative Analysis of Droplet-Based Ultra-High-Throughput Single-Cell RNA-Seq Systems. Mol Cell. 2019 Jan 3;73(1):130-142.e5. doi: 10.1016/j.molcel.2018.10.020. Epub 2018 Nov 21. PMID: 30472192.
Jorgenson LA, Newsome WT, Anderson DJ, Bargmann CI, Brown EN, Deisseroth K, Donoghue JP, Hudson KL, Ling GS, MacLeish PR, Marder E, Normann RA, Sanes JR, Schnitzer MJ, Sejnowski TJ, Tank DW, Tsien RY, Ugurbil K, Wingfield JC. The BRAIN Initiative: developing technology to catalyse neuroscience discovery. Philos Trans R Soc Lond B Biol Sci. 2015 May 19;370(1668):20140164. doi: 10.1098/rstb.2014.0164. PMID: 25823863; PMCID: PMC4387507.
Hawrylycz MJ, Lein ES, Guillozet-Bongaarts AL, Shen EH, Ng L, Miller JA, van de Lagemaat LN, Smith KA, Ebbert A, Riley ZL, Abajian C, Beckmann CF, Bernard A, Bertagnolli D, Boe AF, Cartagena PM, Chakravarty MM, Chapin M, Chong J, Dalley RA, David Daly B, Dang C, Datta S, Dee N, Dolbeare TA, Faber V, Feng D, Fowler DR, Goldy J, Gregor BW, Haradon Z, Haynor DR, Hohmann JG, Horvath S, Howard RE, Jeromin A, Jochim JM, Kinnunen M, Lau C, Lazarz ET, Lee C, Lemon TA, Li L, Li Y, Morris JA, Overly CC, Parker PD, Parry SE, Reding M, Royall JJ, Schulkin J, Sequeira PA, Slaughterbeck CR, Smith SC, Sodt AJ, Sunkin SM, Swanson BE, Vawter MP, Williams D, Wohnoutka P, Zielke HR, Geschwind DH, Hof PR, Smith SM, Koch C, Grant SGN, Jones AR. An anatomically comprehensive atlas of the adult human brain transcriptome. Nature. 2012 Sep 20;489(7416):391-399. doi: 10.1038/nature11405. PMID: 22996553; PMCID: PMC4243026.
Rheaume BA, Jereen A, Bolisetty M, Sajid MS, Yang Y, Renna K, Sun L, Robson P, Trakhtenberg EF. Single cell transcriptome profiling of retinal ganglion cells identifies cellular subtypes. Nat Commun. 2018 Jul 17;9(1):2759. doi: 10.1038/s41467-018-05134-3. Erratum in: Nat Commun. 2018 Aug 7;9(1):3203. PMID: 30018341; PMCID: PMC6050223.
Zeisel A, Hochgerner H, Lönnerberg P, Johnsson A, Memic F, van der Zwan J, Häring M, Braun E, Borm LE, La Manno G, Codeluppi S, Furlan A, Lee K, Skene N, Harris KD, Hjerling-Leffler J, Arenas E, Ernfors P, Marklund U, Linnarsson S. Molecular Architecture of the Mouse Nervous System. Cell. 2018 Aug 9;174(4):999-1014.e22. doi: 10.1016/j.cell.2018.06.021. PMID: 30096314; PMCID: PMC6086934.
Zeisel A, Muñoz-Manchado AB, Codeluppi S, Lönnerberg P, La Manno G, Juréus A, Marques S, Munguba H, He L, Betsholtz C, Rolny C, Castelo-Branco G, Hjerling-Leffler J, Linnarsson S. Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science. 2015 Mar 6;347(6226):1138-42. doi: 10.1126/science.aaa1934. Epub 2015 Feb 19. PMID: 25700174.
Tasic B, Menon V, Nguyen TN, Kim TK, Jarsky T, Yao Z, Levi B, Gray LT, Sorensen SA, Dolbeare T, Bertagnolli D, Goldy J, Shapovalova N, Parry S, Lee C, Smith K, Bernard A, Madisen L, Sunkin SM, Hawrylycz M, Koch C, Zeng H. Adult mouse cortical cell taxonomy revealed by single cell transcriptomics. Nat Neurosci. 2016 Feb;19(2):335-46. doi: 10.1038/nn.4216. Epub 2016 Jan 4. PMID: 26727548; PMCID: PMC4985242.
Menon M, Mohammadi S, Davila-Velderrain J, Goods BA, Cadwell TD, Xing Y, Stemmer-Rachamimov A, Shalek AK, Love JC, Kellis M, Hafler BP. Single-cell transcriptomic atlas of the human retina identifies cell types associated with age-related macular degeneration. Nat Commun. 2019 Oct 25;10(1):4902. doi: 10.1038/s41467-019-12780-8. PMID: 31653841; PMCID: PMC6814749.
Copley MR, Beer PA, Eaves CJ. Hematopoietic stem cell heterogeneity takes center stage. Cell Stem Cell. 2012 Jun 14;10(6):690-697. doi: 10.1016/j.stem.2012.05.006. PMID: 22704509.
Nestorowa S, Hamey FK, Pijuan Sala B, Diamanti E, Shepherd M, Laurenti E, Wilson NK, Kent DG, Göttgens B. A single-cell resolution map of mouse hematopoietic stem and progenitor cell differentiation. Blood. 2016 Aug 25;128(8):e20-31. doi: 10.1182/blood-2016-05-716480. Epub 2016 Jun 30. PMID: 27365425; PMCID: PMC5305050.
Villani AC, Satija R, Reynolds G, Sarkizova S, Shekhar K, Fletcher J, Griesbeck M, Butler A, Zheng S, Lazo S, Jardine L, Dixon D, Stephenson E, Nilsson E, Grundberg I, McDonald D, Filby A, Li W, De Jager PL, Rozenblatt-Rosen O, Lane AA, Haniffa M, Regev A, Hacohen N. Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors. Science. 2017 Apr 21;356(6335):eaah4573. doi: 10.1126/science.aah4573. PMID: 28428369; PMCID: PMC5775029.Cai Y, Dai Y, Wang Y, Yang Q, Guo J, Wei C, Chen W, Huang H, Zhu J, Zhang C, Zheng W, Wen Z, Liu H, Zhang M, Xing S, Jin Q, Feng CG, Chen X. Single-cell transcriptomics of blood reveals a natural killer cell subset depletion in tuberculosis. EBioMedicine. 2020 Mar;53:102686. doi: 10.1016/j.ebiom.2020.102686. Epub 2020 Feb 27. PMID: 32114394; PMCID: PMC7047188.
Cai Y, Dai Y, Wang Y, Yang Q, Guo J, Wei C, Chen W, Huang H, Zhu J, Zhang C, Zheng W, Wen Z, Liu H, Zhang M, Xing S, Jin Q, Feng CG, Chen X. Single-cell transcriptomics of blood reveals a natural killer cell subset depletion in tuberculosis. EBioMedicine. 2020 Mar;53:102686. doi: 10.1016/j.ebiom.2020.102686. Epub 2020 Feb 27. PMID: 32114394; PMCID: PMC7047188.
He L, Vanlandewijck M, Mäe MA, Andrae J, Ando K, Del Gaudio F, Nahar K, Lebouvier T, Laviña B, Gouveia L, Sun Y, Raschperger E, Segerstolpe Å, Liu J, Gustafsson S, Räsänen M, Zarb Y, Mochizuki N, Keller A, Lendahl U, Betsholtz C. Single-cell RNA sequencing of mouse brain and lung vascular and vessel-associated cell types. Sci Data. 2018 Aug 21;5:180160. doi: 10.1038/sdata.2018.160. PMID: 30129931; PMCID: PMC6103262.
Montoro DT, Haber AL, Biton M, Vinarsky V, Lin B, Birket SE, Yuan F, Chen S, Leung HM, Villoria J, Rogel N, Burgin G, Tsankov AM, Waghray A, Slyper M, Waldman J, Nguyen L, Dionne D, Rozenblatt-Rosen O, Tata PR, Mou H, Shivaraju M, Bihler H, Mense M, Tearney GJ, Rowe SM, Engelhardt JF, Regev A, Rajagopal J. A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Nature. 2018 Aug;560(7718):319-324. doi: 10.1038/s41586-018-0393-7. Epub 2018 Aug 1. PMID: 30069044; PMCID: PMC6295155.
Plasschaert LW, Žilionis R, Choo-Wing R, Savova V, Knehr J, Roma G, Klein AM, Jaffe AB. A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte. Nature. 2018 Aug;560(7718):377-381. doi: 10.1038/s41586-018-0394-6. Epub 2018 Aug 1. PMID: 30069046; PMCID: PMC6108322.
Park J, Shrestha R, Qiu C, Kondo A, Huang S, Werth M, Li M, Barasch J, Suszták K. Single-cell transcriptomics of the mouse kidney reveals potential cellular targets of kidney disease. Science. 2018 May 18;360(6390):758-763. doi: 10.1126/science.aar2131. Epub 2018 Apr 5. PMID: 29622724; PMCID: PMC6188645.
Parikh K, Antanaviciute A, Fawkner-Corbett D, Jagielowicz M, Aulicino A, Lagerholm C, Davis S, Kinchen J, Chen HH, Alham NK, Ashley N, Johnson E, Hublitz P, Bao L, Lukomska J, Andev RS, Björklund E, Kessler BM, Fischer R, Goldin R, Koohy H, Simmons A. Colonic epithelial cell diversity in health and inflammatory bowel disease. Nature. 2019 Mar;567(7746):49-55. doi: 10.1038/s41586-019-0992-y. Epub 2019 Feb 27. PMID: 30814735.
Aizarani N, Saviano A, Sagar, Mailly L, Durand S, Herman JS, Pessaux P, Baumert TF, Grün D. A human liver cell atlas reveals heterogeneity and epithelial progenitors. Nature. 2019 Aug;572(7768):199-204. doi: 10.1038/s41586-019-1373-2. Epub 2019 Jul 10. PMID: 31292543; PMCID: PMC6687507.
Han X, Zhou Z, Fei L, Sun H, Wang R, Chen Y, Chen H, Wang J, Tang H, Ge W, Zhou Y, Ye F, Jiang M, Wu J, Xiao Y, Jia X, Zhang T, Ma X, Zhang Q, Bai X, Lai S, Yu C, Zhu L, Lin R, Gao Y, Wang M, Wu Y, Zhang J, Zhan R, Zhu S, Hu H, Wang C, Chen M, Huang H, Liang T, Chen J, Wang W, Zhang D, Guo G. Construction of a human cell landscape at single-cell level. Nature. 2020 May;581(7808):303-309. doi: 10.1038/s41586-020-2157-4. Epub 2020 Mar 25. PMID: 32214235.
Vickovic S, Eraslan G, Salmén F, Klughammer J, Stenbeck L, Schapiro D, Äijö T, Bonneau R, Bergenstråhle L, Navarro JF, Gould J, Griffin GK, Borg Å, Ronaghi M, Frisén J, Lundeberg J, Regev A, Ståhl PL. High-definition spatial transcriptomics for in situ tissue profiling. Nat Methods. 2019 Oct;16(10):987-990. doi: 10.1038/s41592-019-0548-y. Epub 2019 Sep 9. PMID: 31501547; PMCID: PMC6765407.
Rodriques SG, Stickels RR, Goeva A, Martin CA, Murray E, Vanderburg CR, Welch J, Chen LM, Chen F, Macosko EZ. Slide-seq: A scalable technology for measuring genome-wide expression at high spatial resolution. Science. 2019 Mar 29;363(6434):1463-1467. doi: 10.1126/science.aaw1219. Epub 2019 Mar 28. PMID: 30923225; PMCID: PMC6927209.
Nichterwitz S, Chen G, Aguila Benitez J, Yilmaz M, Storvall H, Cao M, Sandberg R, Deng Q, Hedlund E. Laser capture microscopy coupled with Smart-seq2 for precise spatial transcriptomic profiling. Nat Commun. 2016 Jul 8;7:12139. doi: 10.1038/ncomms12139. PMID: 27387371; PMCID: PMC4941116.
Eng CL, Lawson M, Zhu Q, Dries R, Koulena N, Takei Y, Yun J, Cronin C, Karp C, Yuan GC, Cai L. Transcriptome-scale super-resolved imaging in tissues by RNA seqFISH. Nature. 2019 Apr;568(7751):235-239. doi: 10.1038/s41586-019-1049-y. Epub 2019 Mar 25. PMID: 30911168; PMCID: PMC6544023.
Xue Y, Liu D, Cui G, Ding Y, Ai D, Gao S, Zhang Y, Suo S, Wang X, Lv P, Zhou C, Li Y, Chen X, Peng G, Jing N, Han JJ, Liu F. A 3D Atlas of Hematopoietic Stem and Progenitor Cell Expansion by Multi-dimensional RNA-Seq Analysis. Cell Rep. 2019 Apr 30;27(5):1567-1578.e5. doi: 10.1016/j.celrep.2019.04.030. PMID: 31042481.
Burkhard SB, Bakkers J. Spatially resolved RNA-sequencing of the embryonic heart identifies a role for Wnt/β-catenin signaling in autonomic control of heart rate. Elife. 2018 Feb 5;7:e31515. doi: 10.7554/eLife.31515. PMID: 29400650; PMCID: PMC5815850.
Berglund E, Maaskola J, Schultz N, Friedrich S, Marklund M, Bergenstråhle J, Tarish F, Tanoglidi A, Vickovic S, Larsson L, Salmén F, Ogris C, Wallenborg K, Lagergren J, Ståhl P, Sonnhammer E, Helleday T, Lundeberg J. Spatial maps of prostate cancer transcriptomes reveal an unexplored landscape of heterogeneity. Nat Commun. 2018 Jun 20;9(1):2419. doi: 10.1038/s41467-018-04724-5. PMID: 29925878; PMCID: PMC6010471.
Asp M, Giacomello S, Larsson L, Wu C, Fürth D, Qian X, Wärdell E, Custodio J, Reimegård J, Salmén F, Österholm C, Ståhl PL, Sundström E, Åkesson E, Bergmann O, Bienko M, Månsson-Broberg A, Nilsson M, Sylvén C, Lundeberg J. A Spatiotemporal Organ-Wide Gene Expression and Cell Atlas of the Developing Human Heart. Cell. 2019 Dec 12;179(7):1647-1660.e19. doi: 10.1016/j.cell.2019.11.025. PMID: 31835037.
Baccin C, Al-Sabah J, Velten L, Helbling PM, Grünschläger F, Hernández-Malmierca P, Nombela-Arrieta C, Steinmetz LM, Trumpp A, Haas S. Combined single-cell and spatial transcriptomics reveal the molecular, cellular and spatial bone marrow niche organization. Nat Cell Biol. 2020 Jan;22(1):38-48. doi: 10.1038/s41556-019-0439-6. Epub 2019 Dec 23. PMID: 31871321; PMCID: PMC7610809.
Moncada R, Barkley D, Wagner F, Chiodin M, Devlin JC, Baron M, Hajdu CH, Simeone DM, Yanai I. Integrating microarray-based spatial transcriptomics and single-cell RNA-seq reveals tissue architecture in pancreatic ductal adenocarcinomas. Nat Biotechnol. 2020 Mar;38(3):333-342. doi: 10.1038/s41587-019-0392-8. Epub 2020 Jan 13. Erratum in: Nat Biotechnol. 2020 Dec;38(12):1476. PMID: 31932730.
Mimitou EP, Cheng A, Montalbano A, Hao S, Stoeckius M, Legut M, Roush T, Herrera A, Papalexi E, Ouyang Z, Satija R, Sanjana NE, Koralov SB, Smibert P. Multiplexed detection of proteins, transcriptomes, clonotypes and CRISPR perturbations in single cells. Nat Methods. 2019 May;16(5):409-412. doi: 10.1038/s41592-019-0392-0. Epub 2019 Apr 22. PMID: 31011186; PMCID: PMC6557128.