Granted Patent
B2
US 12,359,200 · App. 16/754,714 · Granted Jul 15, 2025
Methods and compositions for expansion of cell population
Inventors:
Zhenrui Li (Kansas City, KS); Pengxu Qian (Kansas City, MO); Linheng Li (Kansas City, MO); Chuan He (Chicago, IL)
View Patent ↗
Loading inventors, assignments & file history…
Abstract
The present invention relates to methods for expanding a stem cell population, as well as other cell populations. More particularly, the invention relates, inter alia, to methods and compositions for expanding a stem cell and/or other cell population, particularly a hematopoietic stem cell population.
Claims (13)
1. A method for expanding a population of hematopoietic stem cells (HSCs) obtained from a tissue selected from the group consisting of peripheral blood, cord blood, and bone marrow, the method comprising modulating an N 6 -Methyladenosine (m 6 A) mRNA modification pathway in the population of stem cells, to expand the number of stem cells,
wherein modulating the m 6 A mRNA modification pathway comprises knocking out or knocking down expression of the Ythdf2 gene.
2. The method according to claim 1 , wherein knocking out expression of the Ythdf2 gene comprises exposing the stem cells to an Mx1-Cre targeting system that inactivates or deletes the Ythdf2 gene.
3. The method according to claim 1 , wherein the expansion of the stem cells is by a factor of at least 2-fold.
4. The method according to claim 3 , wherein the expansion of the stem cells is by a factor of at least 4-fold.
5. The method according to claim 4 , wherein the expansion of the stem cells is by a factor of at least 5-fold.
6. The method according to claim 5 , wherein the expansion of the stem cells is by a factor of at least 8-fold.
7. The method according to claim 6 , wherein the expansion of the stem cells is by a factor of at least 10-fold.
8. The method according to claim 1 , wherein the expanded cells have at least a 5-fold increase in total colony-forming units (CFU).
9. The method according to claim 1 , wherein the expanded cells have at least a 3.8-fold increase in CFU-granulocyte erythrocyte monocyte megakaryocyte (GEMM) colonies.
10. The method according to claim 1 , wherein knocking down expression of the Ythdf2 gene comprises introducing an shRNA into the stem cells to reduce expression of the Ythdf2 gene.
11. The method according to claim 10 , wherein the shRNA is introduced by contacting the stem cells with a lentivirus to deliver the shRNA.
12. The method according to claim 10 , wherein the shRNA has the sequence: 5′-AAGGACGTTCCCAATAGCCAA-3′ (SEQ ID NO 8).
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Apr 14, 2022
From: LI, ZHENRUI; QIAN, PENGXU; LI, LINHENG
To: STOWERS INSTITUTE FOR MEDICAL RESEARCH
Reel/Frame 059599/0028 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Apr 14, 2022
From: HE, CHUAN
To: THE UNIVERSITY OF CHICAGO
Reel/Frame 059599/0137 →
Continuity (3)
Provisional Application
62695820
· Jul 9, 2018
Provisional Application
62570076
· Oct 9, 2017
References Cited (149)
US 9439928B2
· Kasahara et al.
· 2016
[cited by applicant]
US 20160264934A1
· Giallourakis et al.
· 2016
[cited by applicant]
JP 2023171952
· 2023
[cited by applicant]
WO 2012027376
· 2012
[cited by applicant]
Ma (et al. 2009. Adult neural stem cells in the mammalian central nervous system. Cell Res. 19:672-682) (Year: 2009).
[cited by examiner]
Lo (and Parham. 2009. Ethical Issues in Stem Cell Research. Endocrine Re. 30[3]:204-213) (Year: 2009).
[cited by examiner]
Selem (et al. 2011. Cardiac Stem Cells: Biology and Therapeutic Applications. Chapter 19 in Principles of Regenerative Medicine. Elsevier) (Year: 2011).
[cited by examiner]
Wang (et al. 2014. N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells. Nature Cell Biol. 16[2]:191-198) (Year: 2014).
[cited by examiner]
Caplan (2015. Are All Adult Stem Cells the Same. Regen. Eng. Transl. Med. 1:4-10) (Year: 2015).
[cited by examiner]
Mayani (2016. The regulation of hematopoietic stem cell populations. F1000Research 5:1524) (Year: 2016).
[cited by examiner]
Velasco (-Hernandez et al. 2016. Potential Pitfalls of the Mx1-Cre System: Implications for Experimental Modeling of Normal and Malignant Hematopoiesis. Stem Cell Rep. 7[1]:11-18) (Year: 2016).
[cited by examiner]
Faulds (2016. Regulation of m6A mRNA Methylation and Stem Cell Pluripotency Through GSK-3. MS Thesis. Retrieved from ProQuest.com on Aug. 20, 2024) (Year: 2016).
[cited by examiner]
Wu (et al. 2019. m6A methylation controls pluripotency of porcine induced pluripotent stem cells by targeting SOCS3/JAK2/STAT3 pathway in a YTHDF1/YTHDF2-orchestrated manner. Cell Death Dis. 10:1071) (Year: 2019).
[cited by examiner]
Huang (et al. 2021. N6-methyladenosine methyltransferases: functions, regulation, and clinical potential. J. Hematol. Oncol. 14:117) (Year: 2021).
[cited by examiner]
Wendler (2022. Autologous stem cell transplants: What to expect. Available online at mdanderson.org. Accessed Aug. 21, 2024) (Year: 2022).
[cited by examiner]
Kwok (et al. 2017. Genetic alterations of m6A regulators predict poorer survival in acute myeloid leukemia. J. Hematol. Oncol. 10:39) (Year: 2017).
[cited by examiner]
Zhang, et al. “m6A Demethylase ALKBH5 Maintains Tumorigenicity of Glioblastoma Stem-like Cells by Sustaining FOXM1 Expression and Cell Proliferation Program,” Cancer Cell 31, 591-606 e596 (2017).
[cited by applicant]
Lence, et al. “m6A modulates neuronal functions and sex determination in
[cited by applicant]
Haussmann, et al. “m6A potentiates Sxl alternative pre-mRNA splicing for robust
[cited by applicant]
Chen, et al. “m(6)A RNA methylation is regulated by microRNAs and promotes reprogramming to pluripotency,” Cell Stem Cell 16, 289-301 (2015).
[cited by applicant]
Alarcon, et al. “N6-methyladenosine marks primary microRNAs for processing,” Nature 519, 482-485 (2015).
[cited by applicant]
Xiao, et al. “Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing,” Molecular Cell 61, 507-519 (2016).
[cited by applicant]
Wojtas, et al. “Regulation of m6A Transcripts by the 3′->5′ RNA Helicase YTHDC2 Is Essential for a Successful Meiotic Program in the Mammalian Germline,” Molecular Cell 68, 374-387 e312 (2017).
[cited by applicant]
Ivanova, et al. “The RNA m6A Reader YTHDF2 Is Essential for the Post-transcriptional Regulation of the Maternal Transcriptome and Oocyte Competence,” Molecular Cell 67, 1059-1067 e1054 (2017).
[cited by applicant]
Fustin, et al. “RNA-methylation-dependent RNA processing controls the speed of the circadian clock,” Cell 155, 793-806 (2013).
[cited by applicant]
Slobodin, et al. “Transcription Impacts the Efficiency of mRNA Translation via Co-transcriptional N6-adenosine Methylation,” Cell 169, 326-337 e312 (2017).
[cited by applicant]
Schwartz, et al. “Transcriptome-wide mapping reveals widespread dynamic-regulated pseudouridylation of ncRNA and mRNA,” Cell 159, 148-162 (2014).
[cited by applicant]
Pendleton, et al. “The U6 snRNA m6A Methyltransferase METTL16 Regulates SAM Synthetase Intron Retention,” Cell 169, 824-835 e814 (2017).
[cited by applicant]
Shi, et al. “YTHDF3 facilitates translation and decay of N6-methyladenosine-modified RNA,” Cell Research 27, 315-328 (2017).
[cited by applicant]
Huang, et al. “Recognition of RNA N(6)-methyladenosine by IGF2BP proteins enhances mRNA stability and translation,” Nature Cell Biology 20, 285-295 (2018).
[cited by applicant]
Bertero, et al. “The SMAD2/3 interactome reveals that TGFbeta controls m(6)A mRNA methylation in pluripotency,” Nature (2018).
[cited by applicant]
Liu, et al. “N(6)-methyladenosine-dependent RNA structural switches regulate RNA-protein interactions,” Nature 518, 560-564 (2015).
[cited by applicant]
Joseph, et al. “Deciphering hematopoietic stem cells in their niches: a critical appraisal of genetic models, lineage tracing, and imaging strategies,” Cell Stem Cell 13, 520-533 (2013).
[cited by applicant]
Zhou, et al. “Tracing haematopoietic stem cell formation at single-cell resolution,” Nature 533, 487-492 (2016).
[cited by applicant]
He, et al. “Mechanisms of stem cell self-renewal,” Annual Review of Cell and Developmental Biology 25, 377-406 (2009).
[cited by applicant]
Qian, et al. “The Dlk1-Gtl2 Locus Preserves LT-HSC Function by Inhibiting the PI3K-mTOR Pathway to Restrict Mitochondrial Metabolism,” Cell Stem Cell 18, 214-228 (2016).
[cited by applicant]
He, et al. “Homing and migration assays of hematopoietic stem/progenitor cells,” Methods in Molecular Biology 1185, 279-284 (2014).
[cited by applicant]
Hu & Smyth “ELDA: extreme limiting dilution analysis for comparing depleted and enriched populations in stem cell and other assays,” Journal of Immunological Methods 347, 70-78 (2009).
[cited by applicant]
Purton & Scadden, “Limiting factors in murine hematopoietic stem cell assays,” Cell Stem Cell 1, 263-270 (2007).
[cited by applicant]
Perry, et al. Cooperation between both Wnt/{beta}-catenin and PTEN/PI3K/Akt signaling promotes primitive hematopoietic stem cell self-renewal and expansion, Genes & Development 25, 1928-1942 (2011).
[cited by applicant]
Simsek, et al. “The Mammalian Ribo-interactome Reveals Ribosome Functional Diversity and Heterogeneity,” Cell 169, 1051-1065 e1018 (2017).
[cited by applicant]
Acar, et al. “Deep imaging of bone marrow shows non-dividing stem cells are mainly perisinusoidal,” Nature 526, 126-130 (2015).
[cited by applicant]
Arai, et al. “Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche,” Cell 118, 149-161 (2004).
[cited by applicant]
Beerman, et al. “Quiescent hematopoietic stem cells accumulate DNA damage during aging that is repaired upon entry into cell cycle,” Cell Stem Cell 15, 37-50 (2014).
[cited by applicant]
Benveniste, et al. “Intermediate-term hematopoietic stem cells with extended but time-limited reconstitution potential,” Cell stem cell 6, 48-58 (2010).
[cited by applicant]
Benz, et al. “Hematopoietic stem cell subtypes expand differentially during development and display distinct lymphopoietic programs,” Cell Stem Cell 10, 273-283 (2012).
[cited by applicant]
Bowers, et al. “Osteoblast ablation reduces normal long-term hematopoietic stem cell self-renewal but accelerates leukemia development,” Blood 125, 2678-2688 (2015).
[cited by applicant]
Bruns, et al. “Megakaryocytes regulate hematopoietic stem cell quiescence through CXCL4 secretion,” Nat Med 20(11), 1315-1320 (2014).
[cited by applicant]
Calvi, et al. “Osteoblastic cells regulate the haematopoietic stem cell niche,” Nature 425, 841-846 (2003).
[cited by applicant]
Chen, et al. “Hoxb5 marks long-term haematopoietic stem cells and reveals a homogenous perivascular niche,” Nature 530, 223-227 (2016).
[cited by applicant]
Dacic, et al. “Col1a1-driven transgenic markers of osteoblast lineage progression,” J Bone Miner Res 16, 1228-1236 (2001).
[cited by applicant]
Ding & Morrison “Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches,” Nature 495, 231-235 (2013).
[cited by applicant]
Ding, et al. “Endothelial and perivascular cells maintain haematopoietic stem cells,” Nature 481, 457-462 (2012).
[cited by applicant]
Dominici, et al. “Restoration and reversible expansion of the osteoblastic hematopoietic stem cell niche after marrow radioablation,” Blood 114, 2333-2343 (2009).
[cited by applicant]
Fleming, et al. “Functional heterogeneity is associated with the cell cycle status of murine hematopoietic stem cells,” The Journal of cell biology 122, 897-902 (1993).
[cited by applicant]
Foudi, et al. “Analysis of histone 2B-GFP retention reveals slowly cycling hematopoietic stem cells,” Nature biotechnology (2008).
[cited by applicant]
Gazit, et al. “Fgd5 identifies hematopoietic stem cells in the murine bone marrow,” The Journal of experimental medicine 211, 1315-1331 (2014).
[cited by applicant]
Greenbaum, et al. “CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance,” Nature 495, 227-230 (2013).
[cited by applicant]
Haug, et al. “N-cadherin expression level distinguishes reserved versus primed states of hematopoietic stem cells,” Cell stem cell 2, 367-379 (2008).
[cited by applicant]
Hooper, et al. “Engraftment and reconstitution of hematopoiesis is dependent on VEGFR2-mediated regeneration of sinusoidal endothelial cells,” Cell Stem Cell 4, 263-274 (2009).
[cited by applicant]
Itkin, et al. “Corrigendum: Distinct bone marrow blood vessels differentially regulate haematopoiesis,” Nature 538, 274 (2016).
[cited by applicant]
Kiel, et al. “SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells,” Cell 121, 1109-1121 (2005).
[cited by applicant]
Kunisaki, et al. “Arteriolar niches maintain haematopoietic stem cell quiescence,” Nature (2013).
[cited by applicant]
Lerner and Harrison, “5-Fluorouracil spares hemopoietic stem cells responsible for longterm repopulation,” Experimental hematology 18, 114-118 (1990).
[cited by applicant]
Longley, et al. “5-fluorouracil: mechanisms of action and clinical strategies,” Nature reviews Cancer 3, 330-338 (2003).
[cited by applicant]
Walter, et al. “Exit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells,” Nature 520, 549-552 (2015).
[cited by applicant]
Mendelson and Frenette, “Hematopoietic stem cell niche maintenance during homeostasis and regeneration,” Nat Med 20, 833-846 (2014).
[cited by applicant]
Mendez-Ferrer, et al. “Mesenchymal and haematopoietic stem cells form a unique bone marrow niche,” Nature 466, 829-834 (2010).
[cited by applicant]
Morita, et al. “Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment,” The Journal of experimental medicine 207, 1173-1182.
[cited by applicant]
Nilsson, et al. “Spatial localization of transplanted hemopoietic stem cells: inferences for the localization of stem cell niches,” Blood 97, 2293-2299 (2001).
[cited by applicant]
Park, et al. “Association of Lbc Rho guanine nucleotide exchange factor with alpha-catenin-related protein, alpha-catulin/CTNNAL1, supports serum response factor activation,” The Journal of biological chemistry 277, 453…
[cited by applicant]
Qian, et al. “The Dlk1-Gtl2 Locus Preserves LT-HSC Function by Inhibiting the PI3K-mTOR Pathway to Restrict Mitochondrial Metabolism,” Cell stem cell (2015).
[cited by applicant]
Raghunath, et al. “Advancing cartilage tissue engineering: the application of stem cell technology,” Current opinion in biotechnology 16, 503509 (2005).
[cited by applicant]
Rodina, et al. “The epichaperome is an integrated chaperome network that facilitates tumour survival,” Nature 538, 397-401 (2016).
[cited by applicant]
Sanjuan-Pla, et al. “Platelet-biased stem cells reside at the apex of the haematopoietic stem-cell hierarchy,” Nature (2013).
[cited by applicant]
Scadden, “Nice Neighborhood: Emerging Concepts of the Stem Cell Niche. Cell /57, 41-50. Schofield, R. (1978). The relationship between the spleen colony-forming cell and the haemopoietic stem cell,” Blood Cells 4, 7-25 …
[cited by applicant]
Sophia Fox, et al. “The basic science of articular cartilage: structure, composition, and function.,” Sports Health 1(6), 461-468 (2009).
[cited by applicant]
Sugimura, et al. “Noncanonical Wnt signaling maintains hematopoietic stem cells in the niche,” Cell 150, 351-365 (2012).
[cited by applicant]
Sugiyama, et al. “Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches,” Immunity 25, 977988 (2006).
[cited by applicant]
Takubo, et al. “Regulation of glycolysis by pdk functions as a metabolic checkpoint for cell cycle quiescence in hematopoietic stem cells,” Cell stem cell 3;12, 49-61 (2013).
[cited by applicant]
Venkatraman, et al. “Maternal-imprinting at H19-Igf2 locus maintains adult hematopoietic stem cell quiescence,” Nature 500, 345-349 (2013).
[cited by applicant]
Wagers and Weissman Differential expression of {alpha}2 integrin separates long-term and short-term reconstituting Lin-/loThy1.1loc-kit+Sca-1+ hematopoietic stem cells. Stem cells (Dayton, Ohio) 24(4):1087-94.
[cited by applicant]
Tirumuru, et al. “N6-methyladenosine of HIV-1 RNA regulates viral infection and HIV-1 Gag protein expression,” eLife Microbilogy and Infectious Disease Jul. 2, 2016 vol. 5, No. e15528.
[cited by applicant]
Wilson, et al. “Hematopoietic Stem Cells Reversibly Switch from Dormancy to Self-Renewal during Homeostasis and Repair,” Cell 135, 1118-1129 (2008).
[cited by applicant]
Xie, et al. “Detection of functional haematopoietic stem cell niche using real-time imaging,” Nature 457, 97-101 (2009).
[cited by applicant]
Yamazaki, et al. “Nonmyelinating schwann cells maintain hematopoietic stem cell hibernation in the bone marrow niche,” Cell 147, 1146-1158 (2011).
[cited by applicant]
Yang, et al. “Osteogenic fate of hypertrophic chondrocytes,” Cell research 24, 1266-1269 (2014).
[cited by applicant]
Yang, et al. “Identification of Lin(−)Sca1(+)kit(+)CD34(+)Flt3-short-term hematopoietic stem cells capable of rapidly reconstituting and rescuing myeloablated transplant recipients,” Blood 105, 2717-2723 (2005).
[cited by applicant]
Zhang, et al. “Identification of the haematopoietic stem cell niche and control of the niche size,” Nature 425, 836-841 (2003).
[cited by applicant]
Zhao, et al. “Megakaryocytes maintain homeostatic quiescence and promote post-injury regeneration of hematopoietic stem cells,” Nat Med 20, 1321-1326 (2014).
[cited by applicant]
Zhou, et al. “Bone marrow adipocytes promote the regeneration of stem cells and haematopoiesis by secreting SCF,” Nature cell biology 19(8), 891-903 (2017).
[cited by applicant]
Morrison and Scadden, “The bone marrow niche for haematopoietic stem cells,” Nature 505, 327-334 (2014).
[cited by applicant]
PCT/US2018/055092 Search Report and Written Opinion dated Mar. 22, 2019.
[cited by applicant]
Li, et al. “Suppression of m6A reader Ythdf2 promotes hematopoietic stem cell expansion,” Cell Research vol. 28, No. 9, Jul. 3, 2018 pp. 904-914.
[cited by applicant]
Extended European Search Report for Application No. 18866285.2 dated Jun. 16, 2021.
[cited by applicant]
Hsieh, et al. “miR-146a-5p circuitry uncouples cell proliferation and migration, but not differentiation, in human mesenchymal stem cells,” Nucleic Acids Research, 2013, vol. 41, No. 21, p. 9753-9763.
[cited by applicant]
Li & Clevers “Coexistence of quiescent and active adult stem cells in mammals,” Science 327, 542-545 (2010).
[cited by applicant]
Weissman, I. L. “Stem cells: units of development, units of regeneration, and units in evolution,” Cell 100, 157-168 (2000).
[cited by applicant]
Walasek, et al. “Hematopoietic stem cell expansion: challenges and opportunities,” Annals of the New York Academy of Sciences 1266, 138-150 (2012).
[cited by applicant]
Sung & Chao, “Concise review: acute graft-versus-host disease: immunobiology, prevention, and treatment,” Stem cells translational medicine 2, 25-32 (2013).
[cited by applicant]
Shlomchik, W. D. “Graft-versus-host disease,” Nature reviews. Immunology 7, 340-352 (2007).
[cited by applicant]
Huang, et al. “Activation of OCT4 enhances ex vivo expansion of human cord blood hematopoietic stem and progenitor cells by regulating HOXB4 expression,” Leukemia 30, 144-153 (2016).
[cited by applicant]
Boitano, et al. “Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells,” Science 329, 1345-1348 (2010).
[cited by applicant]
Fares, et al. “Pyrimidoindole derivatives are agonists of human hematopoietic stem cell self-renewal,” Science (New York, N. Y 345, 1509-1512 (2014).
[cited by applicant]
Amsellem, et al. “Ex vivo expansion of human hematopoietic stem cells by direct delivery of the HOXB4 homeoprotein,” Nature medicine 9, 1423-1427 (2003).
[cited by applicant]
Antonchuk, et al. “HOXB4-induced expansion of adult hematopoietic stem cells ex vivo,” Cell 109, 39-45 (2002).
[cited by applicant]
Rentas, et al. “Musashi-2 attenuates AHR signalling to expand human haematopoietic stem cells,” Nature 532, 508-511 (2016).
[cited by applicant]
Himburg, et al. “Pleiotrophin regulates the expansion and regeneration of hematopoietic stem cells,” Nature medicine 16, 475-482 (2010).
[cited by applicant]
North, et al. “Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis,” Nature 447, 1007-1011 (2007).
[cited by applicant]
Varnum-Finney, et al. “Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling,” Nature medicine 6, 1278-1281 (2000).
[cited by applicant]
Chou, et al. “Fetal hepatic progenitors support long-term expansion of hematopoietic stem cells,” Experimental hematology 41, 479-490 e474 (2013).
[cited by applicant]
Guo, et al. “Antagonism of PPAR-gamma signaling expands human hematopoietic stem and progenitor cells by enhancing glycolysis,” Nature medicine 24, 360-367 (2018).
[cited by applicant]
Zhao, et al. “Post-transcriptional gene regulation by mRNA modifications,” Nature reviews. Molecular cell biology 18, 31-42 (2017).
[cited by applicant]
Roundtree, et al. “Dynamic RNA Modifications in Gene Expression Regulation,” Cell 169, 1187-1200 (2017).
[cited by applicant]
Li & Mason “The pivotal regulatory landscape of RNA modifications,” Annual review of genomics and human genetics 15, 127-150 (2014).
[cited by applicant]
Batista, et al. “m(6)A RNA modification controls cell fate transition in mammalian embryonic stem cells,” Cell stem cell 15, 707-719 (2014).
[cited by applicant]
Geula, et al. “Stem cells. m6A mRNA methylation facilitates resolution of naive pluripotency toward differentiation,” Science 347, 1002-1006 (2015).
[cited by applicant]
Yoon, et al. “Temporal Control of Mammalian Cortical Neurogenesis by m6A Methylation,” Cell 171, 877-889 (2017).
[cited by applicant]
Zhang, et at. “m6A modulates haematopoietic stem and progenitor cell specification,” Nature 549, 273-276 (2017).
[cited by applicant]
Zhao, et al. “m6A-dependent maternal mRNA clearance facilitates zebrafish maternal-to-zygotic transition,” Nature 542, 475-478 (2017).
[cited by applicant]
Li, et at. “FTO Plays an Oncogenic Role in Acute Myeloid Leukemia as a N6-Methyladenosine RNA Demethylase,” Cancer cell 31, 127-141 (2017).
[cited by applicant]
Vu, et al. “The N6-methyladenosine (m6A)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells,” Nature medicine 23, 1369-1376 (2017).
[cited by applicant]
Weng, et al. “METTL14 Inhibits Hematopoietic Stem/Progenitor Differentiation and Promotes Leukemogenesis via mRNA m(6)A Modification,” Cell stem cell 22, 191-205 e199 (2018).
[cited by applicant]
Barbieri, et al. “Promoter-bound METTL3 maintains myeloid leukaemia by m(6)A-dependent translation control,” Nature 552, 126-131 (2017).
[cited by applicant]
Wang, et al. “N6-methyladenosine-dependent regulation of messenger RNA stability,” Nature 505, 117-120 (2014).
[cited by applicant]
Meyer, et al. “Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons,” Cell 149, 1635-1646 (2012).
[cited by applicant]
Schwartz, et al. “High-resolution mapping reveals a conserved, widespread, dynamic mRNA methylation program in yeast meiosis,” Cell 155, 1409-1421 (2013).
[cited by applicant]
Dominissini, et al. “Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq,” Nature 485, 201-206 (2012).
[cited by applicant]
Wang, et al. “Conditional deletion of STAT5 in adult mouse hematopoietic stem cells causes loss of quiescence and permits efficient nonablative stem cell replacement,” Blood 113, 4856-4865 (2009).
[cited by applicant]
Ebina, et al. “Transcription factor-mediated reprogramming toward hematopoietic stem cells,” The EMBO journal 34, 694-709 (2015).
[cited by applicant]
Orkin & Zon, “Hematopoiesis: an evolving paradigm for stem cell biology,” Cell 132, 631-644 (2008).
[cited by applicant]
De Pater, et al., “Gata2 is required for HSC generation and survival,” The Journal of experimental medicine 210, 2843-2850 (2013).
[cited by applicant]
Hock, et al. “Tel/Etv6 is an essential and selective regulator of adult hematopoietic stem cell survival,” Genes & development 18, 2336-2341 (2004).
[cited by applicant]
Lim, et at. “Conditional Gata2 inactivation results in HSC loss and lymphatic mispatterning,” The Journal of clinical investigation 122, 3705-3717 (2012).
[cited by applicant]
Reynaud, et al. “SCL/TAL1 expression level regulates human hematopoietic stem cell self-renewal and engraftment,” Blood 106, 2318-2328 (2005).
[cited by applicant]
Kato, et al. “Selective activation of STAT5 unveils its role in stem cell self-renewal in normal and leukemic hematopoiesis,” The Journal of experimental medicine 202, 169-179 (2005).
[cited by applicant]
Li, et al. “m6A mRNA methylation controls T cell homeostasis by targeting the IL-7/STAT5/SOCS pathways,” Nature 548, 338-342 (2017).
[cited by applicant]
Pinto do O, et al. “Expression of the LIM-homeobox gene LH2 generates immortalized steel factor-dependent multipotent hematopoietic precursors,” The EMBO journal 17, 5744-5756 (1998).
[cited by applicant]
Zarnegar, et al. “irCLIP platform for efficient characterization of protein-RNA interactions,” Nature methods 13, 489-492 (2016).
[cited by applicant]
Sheth & Parker, et al. “Decapping and decay of messenger RNA occur in cytoplasmic processing bodies,” Science 300, 805-808 (2003).
[cited by applicant]
Kedersha & Anderson, “Mammalian stress granules and processing bodies,” Methods in enzymology 431, 61-81 (2007).
[cited by applicant]
Lacombe, et al. “Scl regulates the quiescence and the long-term competence of hematopoietic stem cells,” Blood 115, 792-803 (2010).
[cited by applicant]
Galan-Caridad, J. M. et al. Zfx controls the self-renewal of embryonic and hematopoietic stem cells. Cell 129, 345-357 (2007).
[cited by applicant]
Zheng, et al. “ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility,” Molecular cell 49, 18-29 (2013).
[cited by applicant]
Zhou, et al. “Dynamic m(6)A mRNA methylation directs translational control of heat shock response,” Nature 526, 591-594 (2015).
[cited by applicant]
Alarcon, et al. “HNRNPA2B1 Is a Mediator of m(6)A-Dependent Nuclear RNA Processing Events,” Cell 162, 1299-1308 (2015).
[cited by applicant]
Zhang, et al. “RNA epigenetic modification: N6-methyladenosine,” Hereditas, 38(4):275-288, Apr. 2016.
[cited by applicant]