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Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Review Article

Targeting Breast Cancer Stem Cells: A Methodological Perspective

Author(s): Marco A. Velasco-Velázquez*, Inés Velázquez-Quesada, Luz X. Vásquez-Bochm and Sonia M. Pérez-Tapia

Volume 14, Issue 5, 2019

Page: [389 - 397] Pages: 9

DOI: 10.2174/1574888X13666180821155701

Price: $65

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Abstract

Cancer Stem Cells (CSCs) constitute a subpopulation at the top of the tumor cell hierarchy that contributes to tumor heterogeneity and is uniquely capable of seeding new tumors. Because of their biological properties, CSCs have been pointed out as therapeutic targets for the development of new therapies against breast cancer. The identification of drugs that selectively target breast CSCs requires a clear understanding of their biological functions and the experimental methods to evaluate such hallmarks. Herein, we review the methods to study breast CSCs properties and discuss their value in the preclinical evaluation of CSC-targeting drugs.

Keywords: Cancer stem cells, anticancer drugs, self-renewal, CSC selective toxicity, CSC differentiation, breast tumors.

[1]
Velasco-Velazquez MA, Homsi N, De La Fuente M, Pestell RG. Breast cancer stem cells. Int J Biochem Cell Biol 2012; 44(4): 573-7.
[2]
Shibue T, Weinberg RA. EMT, CSCs, and drug resistance: The mechanistic link and clinical implications. Nat Rev Clin Oncol 2017; 14(10): 611-29.
[3]
McDermott SP, Wicha MS. Targeting breast cancer stem cells. Mol Oncol 2010; 4(5): 404-19.
[4]
Pattabiraman DR, Weinberg RA. Tackling the cancer stem cells - what challenges do they pose? Nat Rev Drug Discov 2014; 13(7): 497-512.
[5]
Baumann M, Krause M, Hill R. Exploring the role of cancer stem cells in radioresistance. Nat Rev Cancer 2008; 8(7): 545-54.
[6]
Loeffler M, Roeder I. Tissue stem cells: definition, plasticity, heterogeneity, self-organization and models--a conceptual approach. Cells Tissues Organs 2002; 171(1): 8-26.
[7]
Valent P, Bonnet D, Maria R, et al. Cancer stem cell definitions and terminology: The devil is in the details. Nat Rev Cancer 2012; 12(11): 767-75.
[8]
Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer 2005; 5(4): 275-84.
[9]
Lou H, Dean M. Targeted therapy for cancer stem cells: The patched pathway and ABC transporters. Oncogene 2007; 26(9): 1357-60.
[10]
Yu Y. The role of cancer stem cells in relapse of solid tumors. Front Biosci 2012; E4(1): 1528.
[11]
Flemming A. Cancer stem cells: Targeting the root of cancer relapse. Nat Rev Drug Discov 2015; 14(3): 165.
[12]
Creighton CJ, Li X, Landis M, et al. Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc Natl Acad Sci USA 2009; 106(33): 13820-5.
[13]
Chu JE, Allan AL. The role of cancer stem cells in the organ tropism of breast cancer metastasis: A mechanistic balance between the “seed” and the “soil”? Int J Breast Cancer 2012; 2012: 1-12.
[14]
Yu F, Yao H, Zhu P, et al. let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell 2007; 131(6): 1109-23.
[15]
Shafee N, Smith CR, Wei S, et al. Cancer stem cells contribute to cisplatin resistance in Brca1/p53-mediated mouse mammary tumors. Cancer Res 2008; 68(9): 3243-50.
[16]
Velasco-Velazquez MA, Popov VM, Lisanti MP, Pestell RG. The role of breast cancer stem cells in metastasis and therapeutic implications. Am J Pathol 2011; 179(1): 2-11.
[17]
Shiozawa Y, Nie B, Pienta KJ, Morgan TM, Taichman RS. Cancer stem cells and their role in metastasis. Pharmacol Ther 2013; 138(2): 285-93.
[18]
Brabletz T. To differentiate or not - routes towards metastasis. Nat Rev Cancer 2012; 12(6): 425-36.
[19]
Liu H, Patel MR, Prescher JA, et al. Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models. Proc Natl Acad Sci USA 2010; 107(42): 18115-20.
[20]
Klingbeil P, Marhaba R, Jung T, Kirmse R, Ludwig T, Zöller M. CD44 variant isoforms promote metastasis formation by a tumor cell-matrix cross-talk that supports adhesion and apoptosis resistance. Mol Cancer Res 2009; 7(2): 168-79.
[21]
Morel A-P, Lièvre M, Thomas C, Hinkal G, Ansieau S, Puisieux A. Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS One 2008; 3(8)e2888
[22]
Taube JH, Herschkowitz JI, Komurov K, et al. Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes. Proc Natl Acad Sci USA 2010; 107(35): 15449-54.
[23]
Lv J, Shim J. Existing drugs and their application in drug discovery targeting cancer stem cells. Arch Pharm Res 2015; 38(9): 1617-26.
[24]
Wicha MS. Targeting self-renewal, an Achilles’ heel of cancer stem cells. Nat Med 2014; 20(1): 14-5.
[25]
Chen K, Huang Y-h, Chen J-l. Understanding and targeting cancer stem cells: Therapeutic implications and challenges. Acta Pharmacol Sin 2013; 34(6): 732-40.
[26]
Velasco-Velázquez MA, Jiao X, Pestell RG. Breast Cancer Stem CellsCancer Stem Cells Theories and Practice: InTech 2011.
[27]
Zucchi I, Sanzone S, Astigiano S, Pelucchi P, Scotti M, Valsecchi V, et al. The properties of a mammary gland cancer stem cell. Proc Natl Acad Sci USA 2007; 104(25): 10476-81.
[28]
Lin CY, Barry-Holson KQ, Allison KH. Breast cancer stem cells: are we ready to go from bench to bedside? Histopathology 2016; 68(1): 119-37.
[29]
Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003; 100(7): 3983-8.
[30]
Wang L, Duan W, Kang L, et al. Smoothened activates breast cancer stem-like cell and promotes tumorigenesis and metastasis of breast cancer. Biomed Pharmacother 2014; 68(8): 1099-104.
[31]
Yan W, Chen Y, Yao Y, Zhang H, Wang T. Increased invasion and tumorigenicity capacity of CD44+/CD24- breast cancer MCF7 cells in vitro and in nude mice. Cancer Cell Int 2013; 13(1): 62.
[32]
Liu S, Cong Y, Wang D, et al. Breast cancer stem cells transition between epithelial and mesenchymal states reflective of their normal counterparts. Stem Cell Reports 2014; 2(1): 78-91.
[33]
Fillmore CM, Kuperwasser C. Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy. Breast Cancer Res 2008; 10(2): R25.
[34]
Ryspayeva DE, Smolanka II, Dudnichenko AS, et al. Are CD44(+)/CD24(-) cells the assumed cancer stem cells in breast cancer? Exp Oncol 2017; 39(3): 224-8.
[35]
Ahmed MA, Aleskandarany MA, Rakha EA, et al. A CD44(-)/ CD24(+) phenotype is a poor prognostic marker in early invasive breast cancer. Breast Cancer Res Treat 2012; 133(3): 979-95.
[36]
Marchitti SA, Brocker C, Stagos D, Vasiliou V. Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily. Expert Opin Drug Metab Toxicol 2008; 4(6): 697-720.
[37]
Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 2007; 1(5): 555-67.
[38]
Moreb JS. Aldehyde dehydrogenase as a marker for stem cells. Curr Stem Cell Res Ther 2008; 3(4): 237-46.
[39]
Boonyaratanakornkit JB, Yue L, Strachan LR, et al. Selection of tumorigenic melanoma cells using ALDH. J Invest Dermatol 2010; 130(12): 2799-808.
[40]
Raha D, Wilson TR, Peng J, et al. The cancer stem cell marker aldehyde dehydrogenase is required to maintain a drug-tolerant tumor cell subpopulation. Cancer Res 2014; 74(13): 3579-90.
[41]
Sladek NE, Kollander R, Sreerama L, Kiang DT. Cellular levels of aldehyde dehydrogenases (ALDH1A1 and ALDH3A1) as predictors of therapeutic responses to cyclophosphamide-based chemotherapy of breast cancer: a retrospective study. Rational individualization of oxazaphosphorine-based cancer chemotherapeutic regimens. Cancer Chemother Pharmacol 2002; 49(4): 309-21.
[42]
Croker AK, Rodriguez-Torres M, Xia Y, et al. Differential functional roles of ALDH1A1 and ALDH1A3 in mediating metastatic behavior and therapy resistance of human breast cancer cells. Int J Mol Sci 2017; 18(10): pii:E2039
[43]
Marcato P, Dean CA, Pan D, et al. Aldehyde dehydrogenase activity of breast cancer stem cells is primarily due to isoform ALDH1A3 and its expression is predictive of metastasis. Stem Cells 2011; 29(1): 32-45.
[44]
Christ O, Lucke K, Imren S, et al. Improved purification of hematopoietic stem cells based on their elevated aldehyde dehydrogenase activity. Haematologica 2007; 92(9): 1165-72.
[45]
Charafe-Jauffret E, Ginestier C, Iovino F, et al. Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature. Cancer Res 2009; 69(4): 1302-13.
[46]
Croker AK, Goodale D, Chu J, et al. High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic ability. J Cell Mol Med 2009; 13(8B): 2236-52.
[47]
Schwarz-Cruz YCA, Espinosa M, Maldonado V, Melendez-Zajgla J. Advances in the knowledge of breast cancer stem cells. A review. Histol Histopathol 2016; 31(6): 601-12.
[48]
Dontu G, Abdallah WM, Foley JM, et al. In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev 2003; 17(10): 1253-70.
[49]
Dontu G, Jackson KW, McNicholas E, Kawamura MJ, Abdallah WM, Wicha MS. Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells. Breast Cancer Res 2004; 6(6): R605-15.
[50]
Ponti D, Costa A, Zaffaroni N, et al. Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res 2005; 65(13): 5506-11.
[51]
Dontu G, Wicha MS. Survival of mammary stem cells in suspension culture: implications for stem cell biology and neoplasia. J Mammary Gland Biol Neoplasia 2005; 10(1): 75-86.
[52]
Lombardo Y, de Giorgio A, Coombes CR, Stebbing J, Castellano L. Mammosphere formation assay from human breast cancer tissues and cell lines. J Vis Exp 2015; (97): e52671
[53]
Yang A, Qin S, Schulte BA, Ethier SP, Tew KD, Wang GY. MYC inhibition depletes cancer stem-like cells in triple-negative breast cancer. Cancer Res 2017; 77(23): 6641-50.
[54]
Lamb R, Ozsvari B, Lisanti CL, et al. Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: treating cancer like an infectious disease. Oncotarget 2015; 6(7): 4569-84.
[55]
Deshpande AJ, Ahmed F, Buske C. Identification of murine and human acute myeloid leukemia stem cells. Methods Mol Biol 2009; 568: 21-35.
[56]
Hu Y, Smyth GK. ELDA: Extreme limiting dilution analysis for comparing depleted and enriched populations in stem cell and other assays. J Immunol Methods 2009; 347(1-2): 70-8.
[57]
Jiao X, Rizvanov AA, Cristofanilli M, Miftakhova RR, Pestell RG. Breast Cancer Stem Cell Isolation. Methods Mol Biol 2016; 1406: 121-35.
[58]
Jiao X, Velasco-Velazquez MA, Wang M, et al. CCR5 governs DNA damage and breast cancer stem cell expansion. Cancer Res 2018; 78(7): 1657-71.
[59]
Shi P, Liu W. Tala, Wang H, Li F, Zhang H, et al.Metformin suppresses triple-negative breast cancer stem cells by targeting KLF5 for degradation. Cell Discov 2017; 3: 17010.
[60]
Wei W, Tweardy DJ, Zhang M, et al. STAT3 signaling is activated preferentially in tumor-initiating cells in claudin-low models of human breast cancer. Stem Cells 2014; 32(10): 2571-82.
[61]
Vazquez-Santillan K, Melendez-Zajgla J, Jimenez-Hernandez LE, et al. NF-kappaBeta-inducing kinase regulates stem cell phenotype in breast cancer. Sci Rep 2016; 6: 37340.
[62]
El Helou R, Pinna G, Cabaud O, et al. miR-600 Acts as a Bimodal Switch that Regulates Breast Cancer Stem Cell Fate through WNT Signaling. Cell Rep 2017; 18(9): 2256-68.
[63]
Gupta PB, Onder TT, Jiang G, et al. Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 2009; 138(4): 645-59.
[64]
Holliday DL, Speirs V. Choosing the right cell line for breast cancer research. Breast Cancer Res 2011; 13(4): 215.
[65]
Johnson JI, Decker S, Zaharevitz D, et al. Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials. Br J Cancer 2001; 84(10): 1424-31.
[66]
Voskoglou-Nomikos T, Pater JL, Seymour L. Clinical predictive value of the in vitro cell line, human xenograft, and mouse allograft preclinical cancer models. Clin Cancer Res 2003; 9(11): 4227-39.
[67]
Teicher BA. Tumor models for efficacy determination. Mol Cancer Ther 2006; 5(10): 2435-43.
[68]
Hollingshead MG. Antitumor efficacy testing in rodents. J Natl Cancer Inst 2008; 100(21): 1500-10.
[69]
Yakisich JS. System models, assays and endpoint parameters to evaluate anticancer compounds during preclinical screening. Curr Med Chem 2014; 21(35): 3985-98.
[70]
Erol A, Acikgoz E, Guven U, et al. Ribosome biogenesis mediates antitumor activity of flavopiridol in CD44(+)/CD24(-) breast cancer stem cells. Oncol Lett 2017; 14(6): 6433-40.
[71]
Li X, Zhou N, Wang J, et al. Quercetin suppresses breast cancer stem cells (CD44(+)/CD24(-)) by inhibiting the PI3K/Akt/mTOR-signaling pathway. Life Sci 2018; 196: 56-62.
[72]
Meyer MJ, Fleming JM, Ali MA, Pesesky MW, Ginsburg E, Vonderhaar BK. Dynamic regulation of CD24 and the invasive, CD44posCD24neg phenotype in breast cancer cell lines. Breast Cancer Res 2009; 11(6): R82.
[73]
Sajithlal GB, Rothermund K, Zhang F, et al. Permanently blocked stem cells derived from breast cancer cell lines. Stem Cells 2010; 28(6): 1008-18.
[74]
Yu SC, Ping YF, Yi L, et al. Isolation and characterization of cancer stem cells from a human glioblastoma cell line U87. Cancer Lett 2008; 265(1): 124-34.
[75]
Lathia JD, Mack SC, Mulkearns-Hubert EE, Valentim CL, Rich JN. Cancer stem cells in glioblastoma. Genes Dev 2015; 29(12): 1203-17.
[76]
Qiang L, Yang Y, Ma YJ, et al. Isolation and characterization of cancer stem like cells in human glioblastoma cell lines. Cancer Lett 2009; 279(1): 13-21.
[77]
House CD, Hernandez L, Annunziata CM. In vitro enrichment of ovarian cancer tumor-initiating cells. J Vis Exp 2015; (96): e52446
[78]
Martinez-Serrano MJ, Caballero-Banos M, Vilella R, Vidal L, Pahisa J, Martinez-Roman S. Is sphere assay useful for the identification of cancer initiating cells of the ovary? Int J Gynecol Cancer 2015; 25(1): 12-7.
[79]
He M, Fu Y, Yan Y, et al. The Hedgehog signalling pathway mediates drug response of MCF-7 mammosphere cells in breast cancer patients. Clin Sci 2015; 129(9): 809-22.
[80]
Xie G, Zhan J, Tian Y, et al. Mammosphere cells from high-passage MCF7 cell line show variable loss of tumorigenicity and radioresistance. Cancer Lett 2012; 316(1): 53-61.
[81]
Laranjo M, Carvalho MJ, Costa T, et al. Mammospheres of hormonal receptor positive breast cancer diverge to triple-negative phenotype. Breast 2017; 38: 22-9.
[82]
Liu Y, Nenutil R, Appleyard MV, et al. Lack of correlation of stem cell markers in breast cancer stem cells. Br J Cancer 2014; 110(8): 2063-71.
[83]
Jafari SM, Joshaghani HR, Panjehpour M, Aghaei M, Zargar Balajam N. Apoptosis and cell cycle regulatory effects of adenosine by modulation of GLI-1 and ERK1/2 pathways in CD44(+) and CD24(-) breast cancer stem cells. Cell Prolif 2017; 50(4)e12345
[http://dx.doi.org/10.1111/cpr.12345]
[84]
Flamme M, Cressey PB, Lu C, et al. Induction of Necroptosis in Cancer Stem Cells using a Nickel(II)-Dithiocarbamate Phenanthroline Complex. Eur J Chem 2017; 23(40): 9674-82.
[85]
Fuchs E, Chen T. A matter of life and death: Self‐renewal in stem cells. EMBO Rep 2013; 14(1): 39-48.
[86]
Al-Hajj M, Clarke MF. Self-renewal and solid tumor stem cells. Oncogene 2004; 23(43): 7274-82.
[87]
Borah A, Raveendran S, Rochani A, Maekawa T, Kumar DS. Targeting self-renewal pathways in cancer stem cells: clinical implications for cancer therapy. Oncogenesis 2015; 4(11)e177
[88]
Reynolds BA, Weiss S. Clonal and population analyses demonstrate that an EGF-responsive mammalian embryonic CNS precursor is a stem cell. Dev Biol 1996; 175(1): 1-13.
[89]
Qin J, Liu X, Laffin B, Chen X, et al. The PSA(-/lo) prostate cancer cell population harbors self-renewing long-term tumor-propagating cells that resist castration. Cell Stem Cell 2012; 10(5): 556-69.
[90]
Smart CE, Morrison BJ, Saunus JM, et al. In vitro analysis of breast cancer cell line tumourspheres and primary human breast epithelia mammospheres demonstrates inter- and intrasphere heterogeneity. PLoS One 2013; 8(6)e64388
[91]
Montales MT, Rahal OM, Kang J, et al. Repression of mammosphere formation of human breast cancer cells by soy isoflavone genistein and blueberry polyphenolic acids suggests diet-mediated targeting of cancer stem-like/progenitor cells. Carcinogenesis 2012; 33(3): 652-60.
[92]
Clement V, Sanchez P, de Tribolet N, Radovanovic I, Ruiz i Altaba A. HEDGEHOG-GLI1 Signaling Regulates Human Glioma Growth, Cancer Stem Cell Self-Renewal, and Tumorigenicity. Curr Biol 2007; 17(2): 165-72.
[93]
Kreso A, van Galen P, Pedley NM, et al. Self-renewal as a therapeutic target in human colorectal cancer. Nat Med 2014; 20(1): 29-36.
[94]
Zhu L, Ni C, Dong B, et al. A novel hedgehog inhibitor iG2 suppresses tumorigenesis by impairing self‐renewal in human bladder cancer. Cancer Med 2016; 5(9): 2579-86.
[95]
Xu L, Zhang L, Hu C, et al. WNT pathway inhibitor pyrvinium pamoate inhibits the self-renewal and metastasis of breast cancer stem cells. Int J Oncol 2016; 48(3): 1175-86.
[96]
Gattinoni L, Memory T. Cells Officially Join the Stem Cell Club. Immunity 2014; 41(1): 7-9.
[97]
Graef P, Buchholz VR, Stemberger C, et al. Serial Transfer of Single-Cell-Derived Immunocompetence Reveals Stemness of CD8+ Central Memory T Cells. Immunity 2014; 41(1): 116-26.
[98]
Hardt O, Wild S, Oerlecke I, Hofmann K, Luo S, Wiencek Y, et al. Highly sensitive profiling of CD44+/CD24- breast cancer stem cells by combining global mRNA amplification and next generation sequencing: evidence for a hyperactive PI3K pathway. Cancer Lett 2012; 325(2): 165-74.
[99]
Gomez-Miragaya J, Palafox M, Pare L, et al. Resistance to Taxanes in Triple-Negative Breast Cancer Associates with the Dynamics of a CD49f+ Tumor-Initiating Population. Stem Cell Reports 2017; 8(5): 1392-407.
[100]
Sachlos E, Risueño RM, Laronde S, Shapovalova Z, Lee J-HH, Russell J, et al. Identification of drugs including a dopamine receptor antagonist that selectively target cancer stem cells. Cell 2012; 149(6): 1284-97.
[101]
Chadwick K, Wang L, Li L, Menendez P, Murdoch B, Rouleau A, et al. Cytokines and BMP-4 promote hematopoietic differentiation of human embryonic stem cells. Blood 2003; 102(3): 906-15.
[102]
Werbowetski-Ogilvie TE, Bossé M, Stewart M, Schnerch A, Ramos-Mejia V, Rouleau A, et al. Characterization of human embryonic stem cells with features of neoplastic progression. Nat Biotechnol 2009; 27(1): 91-7.
[103]
Ke X-YY, Lin Ng VW, Gao S-JJ, Tong YW, Hedrick JL, Yang YY. Co-delivery of thioridazine and doxorubicin using polymeric micelles for targeting both cancer cells and cancer stem cells. Biomaterials 2014; 35(3): 1096-108.
[104]
Liu H, Lv L, Yang K, Yang K. Chemotherapy targeting cancer stem cells. Am J Cancer Res 2015; 5(3): 880-93.
[105]
Thiagarajan PS, Hitomi M, Hale JS, et al. Development of a Fluorescent Reporter System to Delineate Cancer Stem Cells in Triple-Negative Breast Cancer. Stem Cells 2015; 33(7): 2114-25.
[106]
Liang S, Furuhashi M, Nakane R, et al. Isolation and characterization of human breast cancer cells with SOX2 promoter activity. Biochem Biophys Res Commun 2013; 437(2): 205-11.
[107]
D’Angelo RC, Ouzounova M, Davis A, et al. Notch reporter activity in breast cancer cell lines identifies a subset of cells with stem cell activity. Mol Cancer Ther 2015; 14(3): 779-87.
[108]
Tang B, Raviv A, Esposito D, et al. A flexible reporter system for direct observation and isolation of cancer stem cells. Stem Cell Reports 2015; 4(1): 155-69.
[109]
Schott AF, Landis MD, Dontu G, et al. Preclinical and clinical studies of gamma secretase inhibitors with docetaxel on human breast tumors. Clin Cancer Res 2013; 19(6): 1512-24.
[110]
Smith DC, Eisenberg PD, Manikhas G, et al. A phase I dose escalation and expansion study of the anticancer stem cell agent demcizumab (anti-DLL4) in patients with previously treated solid tumors. Clin Cancer Res 2014; 20(24): 6295-303.
[111]
Wilson NK, Kent DG, Buettner F, et al. Combined Single-Cell Functional and Gene Expression Analysis Resolves Heterogeneity within Stem Cell Populations. Cell Stem Cell 2015; 16(6): 712-24.
[112]
Treutlein B, Brownfield DG, Wu AR, et al. Reconstructing lineage hierarchies of the distal lung epithelium using single-cell RNA-seq. Nature 2014; 509(7500): 371-5.
[113]
Patel AP, Tirosh I, Trombetta JJ, et al. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science 2014; 344(6190): 1396-401.

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