Ectopic miR-125a expression induces long-term repopulating stem cell capacity in mouse and human hematopoietic progenitors
Open accessAbstract
Umbilical cord blood (CB) is a convenient and broadly used source of hematopoietic stem cells (HSCs) for allogeneic stem cell transplantation. However, limiting numbers of HSCs remain a major constraint for its clinical application. Although one feasible option would be to expand HSCs to improve therapeutic outcome, available protocols and the molecular mechanisms governing the self-renewal of HSCs are unclear. Here, we show that ectopic expression of a single microRNA (miRNA), miR-125a, in purified murine and human multipotent progenitors (MPPs) resulted in increased self-renewal and robust long-term multi-lineage repopulation in transplanted recipient mice. Using quantitative proteomics and western blot analysis, we identified a restricted set of miR-125a targets involved in conferring long-term repopulating capacity to MPPs in humans and mice. Our findings offer the innovative potential to use MPPs with enhanced self-renewal activity to augment limited sources of HSCs to improve clinical protocols.
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Enforced expression of transcription factors or microRNAs can generate transplantable stem cells from committed cell types.
“enforced expression of transcription factors or microRNAs has been shown to be able to generate transplantable stem cells from committed cell types.[102][103][104]”
From Aging of hematopoietic stem cells (2018) · cites this paper as [104]
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MicroRNAs: Target Recognition and Regulatory Functions
Bartel, D. P. (2009) · Cell · doi:10.1016/j.cell.2009.01.002 · Cited by 20,068 · cited 2× · see citing works
“(legend continued on next page) 384 Cell Stem Cell 19, 383–396, September 1, 2016 positioning miRNAs as pivotal regulators of cellular homeostasis (Bartel, 2009; Filipowicz et al., 2008). miRNA profiling of hematopoietic stem and progenitor cells (HSPCs) has identified several miRNAs as…”
Cox, J., & Mann, M. (2008) · Nature Biotechnology · doi:10.1038/nbt.1511 · Cited by 14,855 · cited 1× · see citing works
“The raw files were analyzed using MaxQuant version 1.5.2.8 (Cox and Mann, 2008) and standard settings.”
InfluentialOng, S.-E., Blagoev, B., Kratchmarova, I., Kristensen, D. B., Steen, H., Pandey, A., & Mann, M. (2002) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m200025-mcp200 · Cited by 5,574 · cited 2× · see citing works
“To gain more insight in the molecular network of miR-125a targets, we performed stable isotope labeling by amino acids in cell culture (SILAC) proteomics in the 32D murine hematopoietic progenitor cell line (Ong et al., 2002; Ward et al., 1999).”
(2008) · doi:10.1038/nrg2290 · Cited by 5,199 · cited 2× · see citing works
“positioning miRNAs as pivotal regulators of cellular homeostasis (Bartel, 2009; Filipowicz et al., 2008).”
Hu, Y., & Smyth, G. K. (2009) · Journal of Immunological Methods · doi:10.1016/j.jim.2009.06.008 · Cited by 2,091 · cited 1× · see citing works
“HSC frequency was estimated using ELDA software (http://bioinf.wehi.edu.au/software/ elda/; Hu and Smyth, 2009).”
Differentiation and proliferation of hematopoietic stem cells
Ogawa, M. (1993) · Blood · doi:10.1182/blood.v81.11.2844.2844 · Cited by 1,395 · see citing works
Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells
Ito, K., Hirao, A., Arai, F., Takubo, K., Matsuoka, S., Miyamoto, K., Ohmura, M., Naka, K., Hosokawa, K., Ikeda, Y., et al. (2006) · Nature Medicine · doi:10.1038/nm1388 · Cited by 1,362 · cited 2× · see citing works
“These targets include p38 kinase, a negative HSC self-renewal regulator (Ito et al., 2006), and its inhibition leads to ex vivo HSC expansion (Wang et al., 2011), three protein tyrosine phosphatases (Ptpn1, Ptpn7, and Smek1, all known to suppress cytokine signaling and negatively regulate MAP…”
Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis
North, T. E., Goessling, W., Walkley, C. R., Lengerke, C., Kopani, K. R., Lord, A. M., Weber, G. J., Bowman, T. V., Jang, I. H., Großer, T., et al. (2007) · Nature · doi:10.1038/nature05883 · Cited by 1,095 · cited 3× · see citing works
“Recently, promising HSC expansion protocols have employed small molecules such as prostaglandin E2, SR1, UM171, or UM729, although clinical efficacy remains elusive (Boitano et al., 2010; Fares et al., 2014; North et al., 2007).”
Aryl Hydrocarbon Receptor Antagonists Promote the Expansion of Human Hematopoietic Stem Cells
Boitano, A. E., Wang, J., Romeo, R., Bouchez, L. C., Parker, A. E., Sutton, S., Walker, J., Flaveny, C. A., Perdew, G., Denison, M., et al. (2010) · Science · doi:10.1126/science.1191536 · Cited by 1,058 · cited 3× · see citing works
“Recently, promising HSC expansion protocols have employed small molecules such as prostaglandin E2, SR1, UM171, or UM729, although clinical efficacy remains elusive (Boitano et al., 2010; Fares et al., 2014; North et al., 2007).”
Isolation of Single Human Hematopoietic Stem Cells Capable of Long-Term Multilineage Engraftment
Notta, F., Doulatov, S., Laurenti, E., Poeppl, A., Jurisica, I., & Dick, J. E. (2011) · Science · doi:10.1126/science.1201219 · Cited by 919 · cited 1× · see citing works
“We sorted immunophenotypically defined HSC and progenitor cell subsets from human-lineage-depleted CB (Figure S1A) (Doulatov et al., 2010; Notta et al., 2011) to obtain a detailed expression profile ofmature miR-125a.”
PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention
Zhang, J., Grindley, J. C., Yin, T., Jayasinghe, S., He, X. C., Ross, J. T., Haug, J. S., Rupp, D., Porter-Westpfahl, K. S., Wiedemann, L. M., et al. (2006) · Nature · doi:10.1038/nature04747 · Cited by 817 · cited 1× · see citing works
“Cell Stem proliferative disorders that progressed to leukemia (Helgason et al., 1998; Zhang et al., 2006).”
Umbilical cord blood transplantation: the first 25 years and beyond
Ballen, K. K., Gluckman, É., & Broxmeyer, H. E. (2013) · Blood · doi:10.1182/blood-2013-02-453175 · Cited by 710 · cited 1× · see citing works
“However, widespread use of CB is impaired due to insufficient hematopoietic stem cell (HSC) numbers in single CB units, resulting in extended times to full engraftment (Ballen et al., 2013).”
O'Connell, R. M., Rao, D. S., Chaudhuri, A. A., Boldin, M. P., Taganov, K. D., Nicoll, J., Paquette, R. L., & Baltimore, D. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20072108 · Cited by 681 · cited 2× · see citing works
“…in murine cells in secondary and tertiary recipients is in agreement with previous reports (Bousquet et al., 2010; Gerrits et al., 2012; O’Connell et al., 2010) and has been shown to be dependent upon sustained expression of miR-125a (Guo et al., 2012) and dosage (O’Connell et al., 2008, 2010).”
Pyrimidoindole derivatives are agonists of human hematopoietic stem cell self-renewal
Fares, I., Chagraoui, J., Gareau, Y., Gingras, S., Ruel, R., Mayotte, N., Csaszar, E., Knapp, D. J. H. F., Miller, P. H., Ngom, M., et al. (2014) · Science · doi:10.1126/science.1256337 · Cited by 573 · cited 2× · see citing works
“Recently, promising HSC expansion protocols have employed small molecules such as prostaglandin E2, SR1, UM171, or UM729, although clinical efficacy remains elusive (Boitano et al., 2010; Fares et al., 2014; North et al., 2007).”
Helgason, C. D., Damen, J. E., Rosten, P., Grewal, R., Sorensen, P., Chappel, S. M., Borowski, A., Jirik, F., Krystal, G., & Humphries, R. K. (1998) · Genes & Development · doi:10.1101/gad.12.11.1610 · Cited by 556 · cited 2× · see citing works
“Cell Stem proliferative disorders that progressed to leukemia (Helgason et al., 1998; Zhang et al., 2006).”
Species- and cell type-specific requirements for cellular transformation
Rangarajan, A., Hong, S. J., Gifford, A., & Weinberg, R. A. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.07.009 · Cited by 555 · cited 1× · see citing works
“…was never observed in human xenografts through three serial transplantations (30 weeks total), suggesting that the inherent susceptibility of murine cells to oncogenic transformation may contribute to the development of (pre-) malignancy (Balmain and Harris, 2000; Rangarajan et al., 2004).”
Metcalf, D. (2008) · Blood · doi:10.1182/blood-2007-03-079681 · Cited by 527 · see citing works
Doulatov, S. R., Notta, F., Eppert, K., Nguyen, L. T., Ohashi, P. S., & Dick, J. E. (2010) · Nature Immunology · doi:10.1038/ni.1889 · Cited by 510 · cited 2× · see citing works
“We sorted immunophenotypically defined HSC and progenitor cell subsets from human-lineage-depleted CB (Figure S1A) (Doulatov et al., 2010; Notta et al., 2011) to obtain a detailed expression profile ofmature miR-125a.”
O’Connell, R. M., Chaudhuri, A. A., Rao, D. S., Gibson, W. S. J., Balazs, A. B., & Baltimore, D. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1009798107 · Cited by 281 · cited 16× · see citing works
“The development of myeloproliferative disease/leukemia upon miR-125a overexpression in murine cells in secondary and tertiary recipients is in agreement with previous reports (Bousquet et al., 2010; Gerrits et al., 2012; O’Connell et al., 2010) and has been shown to be dependent upon sustained expression of miR-125a (…”
InfluentialOne-Unit versus Two-Unit Cord-Blood Transplantation for Hematologic Cancers
Wagner, J. E., Eapen, M., Carter, S., Wang, Y., Schultz, K. R., Wall, D. A., Bunin, N., Delaney, C. S., Haut, P. R., Margolis, D. M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1405584 · Cited by 275 · see citing works
MicroRNA miR-125b causes leukemia
Bousquet, M., Harris, M. H., Zhou, B., & Lodish, H. F. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016611107 · Cited by 255 · cited 1× · see citing works
“…disease/leukemia upon miR-125a overexpression in murine cells in secondary and tertiary recipients is in agreement with previous reports (Bousquet et al., 2010; Gerrits et al., 2012; O’Connell et al., 2010) and has been shown to be dependent upon sustained expression of miR-125a (Guo et…”
Ooi, A. G. L., Sahoo, D., Adorno, M., Wang, Y., Weissman, I. L., & Park, C. Y. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016218107 · Cited by 219 · cited 8× · see citing works
“Targeted downregulation of miR-125a and miR125b caused reduced HSPC self-renewal in vitro (Guo and Scadden, 2010) and reduced proliferation and blood cell output in vivo (Ooi et al., 2010; Wojtowicz et al., 2014), confirming a pivotal role for miR-125 family members in the molecular control of HSC self-renewal.”
InfluentialAttenuation of miR-126 Activity Expands HSC In Vivo without Exhaustion
Lechman, E. R., Gentner, B., van Galen, P., Giustacchini, A., Saini, M., Boccalatte, F. E., Hiramatsu, H., Restuccia, U., Bachi, A., Voisin, V., et al. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2012.09.001 · Cited by 208 · cited 2× · see citing works
“miRNA profiling of hematopoietic stem and progenitor cells (HSPCs) has identified several miRNAs as differentially expressed and functionally able to govern HSC properties (Gerrits et al., 2012; Lechman et al., 2012; O’Connell et al., 2008, 2010).”
Gentner, B., Visigalli, I., Hiramatsu, H., Lechman, E. R., Ungari, S., Giustacchini, A., Schira, G., Amendola, M., Quattrini, A., Martino, S., et al. (2010) · Science Translational Medicine · doi:10.1126/scitranslmed.3001522 · Cited by 207 · cited 2× · see citing works
“Lentiviral and Retroviral Constructs and Transduction For the human part of the study, the lentiviral vector for ectopic miRNA expression (gain of function) has been described previously (Gentner et al., 2010).”
In vitro and in vivo expansion of hematopoietic stem cells
Sauvageau, G., Iscove, N. N., & Humphries, R. K. (2004) · Oncogene · doi:10.1038/sj.onc.1207942 · Cited by 198 · cited 1× · see citing works
“Multiple efforts have been undertaken to attempt HSC expansion, but these have largely been empirical and rarely successful (Metcalf, 2008; Ogawa, 1993; Sauvageau et al., 2004).”
Barker, J. N., Weisdorf, D. J., & Wagner, J. (2001) · New England Journal of Medicine · doi:10.1056/nejm200106143442417 · Cited by 197 · cited 1× · see citing works
“Transplants combining two unrelated CB units have attempted to overcome the shortfall in HSC number, although improvements are modest (Barker et al., 2001; Wagner et al., 2014).”
Verovskaya, E. V., Broekhuis, M., Zwart, E., Ritsema, M., van Os, R. P., de Haan, G., & Bystrykh, L. V. (2013) · Blood · doi:10.1182/blood-2013-01-481135 · Cited by 175 · cited 1× · see citing works
“Cells were isolated and transduced as described above (see also Verovskaya et al., 2013).”
Uren, A. G., Mikkers, H. M. M., Kool, J., van der Weyden, L., Lund, A. H., Wilson, C. H., Rance, R., Jonkers, J., van Lohuizen, M., Berns, A. J. M., et al. (2009) · Nature Protocols · doi:10.1038/nprot.2009.64 · Cited by 167 · cited 2× · see citing works
“Lentiviral Insertion Site Analysis by Modified Splinkerette PCR To determine the lentiviral integration sites we used a splinkerette PCR approach (Uren et al., 2009) that we modified to be non-restrictive and have increased sensitivity for low DNA input amounts (see Supplemental Experimental Procedures).”
Carcinogenesis in mouse and human cells: parallels and paradoxes
Balmain, A., & Harris, C. C. (2000) · Carcinogenesis · doi:10.1093/carcin/21.3.371 · Cited by 154 · cited 2× · see citing works
“…was never observed in human xenografts through three serial transplantations (30 weeks total), suggesting that the inherent susceptibility of murine cells to oncogenic transformation may contribute to the development of (pre-) malignancy (Balmain and Harris, 2000; Rangarajan et al., 2004).”
Meenhuis, A., van Veelen, P. A., de Looper, H., van Boxtel, N., van den Berge, I. J., Sun, S. M., Taskesen, E., Stern, P., de Ru, A. H., van Adrichem, A. J., et al. (2011) · Blood · doi:10.1182/blood-2011-02-336487 · Cited by 142 · cited 2× · see citing works
“After transduction, GFP+ cells were FACS sorted and expanded prior to stable isotope labeling as previously reported (Meenhuis et al., 2011).”
Self-citationOncomir miR-125b regulates hematopoiesis by targeting the gene Lin28A
Chaudhuri, A. A., So, A. Y., Mehta, A., Minisandram, A., Sinha, N., Jönsson, V. D., Rao, D. S., O’Connell, R. M., & Baltimore, D. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1200677109 · Cited by 141 · cited 1× · see citing works
“Loss of PTPN1 leads to increased numbers of pro- and pre-B cells in the BM (Dubé et al., 2005), similar to previous reports showing increased numbers of pro-B cells upon miR-125b overexpression (Chaudhuri et al., 2012) and correlating with our human CB xenotransplantation data.”
The role of protein tyrosine phosphatase 1B in Ras signaling
Dubé, N., Cheng, A., & Tremblay, M. L. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0304242101 · Cited by 136 · cited 2× · see citing works
“Moreover, deletion of PTPN1 in fibroblasts leads to suppression of Erk signaling (Dubé et al., 2004) and increased insulin growth factor-1 (IGF-1)-induced AKT protein kinase B activity (AKT/PKB) (Buckley et al., 2002).”
Ward, A. C., Smith, L., de Koning, J. P., van Aesch, Y. M., & Touw, I. P. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.21.14956 · Cited by 120 · cited 1× · see citing works
“To gain more insight in the molecular network of miR-125a targets, we performed stable isotope labeling by amino acids in cell culture (SILAC) proteomics in the 32D murine hematopoietic progenitor cell line (Ong et al., 2002; Ward et al., 1999).”
Advances in umbilical cord blood stem cell expansion and clinical translation
Pineault, N., & Abu‐Khader, A. (2015) · Experimental Hematology · doi:10.1016/j.exphem.2015.04.011 · Cited by 115 · cited 2× · see citing works
“…for malignant diseases such as leukemia, myelodysplasia, and myelofibrosis as well as non-malignant disorders such as severe aplastic anemia and congenital immune or enzyme deficiencies, Cell S with >40,000 transplants undertaken worldwide (Aljurf et al., 2014; Pineault and Abu-Khader, 2015).”
Buckley, D. A., Cheng, A., Kiely, P. A., Tremblay, M. L., & O’Connor, R. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.7.1998-2010.2002 · Cited by 114 · cited 2× · see citing works
“, 2004) and increased insulin growth factor-1 (IGF-1)-induced AKT protein kinase B activity (AKT/PKB) (Buckley et al., 2002).”
Essential Role of Synoviolin in Embryogenesis
Yagishita, N., Ohneda, K., Amano, T., Yamasaki, S., Sugiura, A., Tsuchimochi, K., Shin, H., Kawahara, K.-I., Ohneda, O., Ohta, T., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m410863200 · Cited by 107 · cited 1× · see citing works
“…all known to suppress cytokine signaling and negatively regulate MAP kinases), a ubiquitin ligase (Syvn1, shown to block differentiation of embryonic stem cells; Yagishita et al., 2005), and Vps4b and M6pr, which are involved in transport of protein to vesicles and their lysosomal degradation.”
Gerrits, A., Walasek, M. A., Olthof, S. G. M., Weersing, E., Ritsema, M., Zwart, E., van Os, R. P., Bystrykh, L. V., & de Haan, G. (2011) · Blood · doi:10.1182/blood-2011-01-331686 · Cited by 101 · cited 15× · see citing works
“The development of myeloproliferative disease/leukemia upon miR-125a overexpression in murine cells in secondary and tertiary recipients is in agreement with previous reports (Bousquet et al., 2010; Gerrits et al., 2012; O’Connell et al., 2010) and has been shown to be dependent upon sustained expression of miR-125a (…”
InfluentialDubé, N., Bourdeau, A., Heinonen, K. M., Cheng, A., Lee-Loy, A., & Tremblay, M. L. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-1353 · Cited by 94 · cited 2× · see citing works
“Loss of PTPN1 leads to increased numbers of pro- and pre-B cells in the BM (Dubé et al., 2005), similar to previous reports showing increased numbers of pro-B cells upon miR-125b overexpression (Chaudhuri et al.”
Wang, Y., Kellner, J. N., Liu, L., & Zhou, D. (2011) · Stem Cells and Development · doi:10.1089/scd.2010.0413 · Cited by 69 · cited 2× · see citing works
“These targets include p38 kinase, a negative HSC self-renewal regulator (Ito et al., 2006), and its inhibition leads to ex vivo HSC expansion (Wang et al., 2011), three protein tyrosine phosphatases (Ptpn1, Ptpn7, and Smek1, all known to suppress cytokine signaling and negatively regulate MAP…”
Umbilical cord blood transplantation: a maturing technology
Oran, B., & Shpall, E. J. (2012) · Hematology · doi:10.1182/asheducation.v2012.1.215.3798291 · Cited by 62 · see citing works
Complex oncogene dependence in microRNA-125a–induced myeloproliferative neoplasms
Guo, S., Bai, H., Megyola, C. M., Halene, S., Krause, D. S., Scadden, D. T., & Lü, J. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1213196109 · Cited by 43 · cited 2× · see citing works
“…in murine cells in secondary and tertiary recipients is in agreement with previous reports (Bousquet et al., 2010; Gerrits et al., 2012; O’Connell et al., 2010) and has been shown to be dependent upon sustained expression of miR-125a (Guo et al., 2012) and dosage (O’Connell et al., 2008, 2010).”
RNAi screen identifies MAPK14 as a druggable suppressor of human hematopoietic stem cell expansion
Baudet, A., Karlsson, C., Talkhoncheh, M. S., Galeev, R., Magnusson, M., & Larsson, J. (2012) · Blood · doi:10.1182/blood-2012-01-403949 · Cited by 42 · cited 1× · see citing works
“Chemical inhibitors of p38 activity have previously shown efficacy in ex vivo mouse and human HSC expansion protocols (Baudet et al., 2012; Wang et al., 2011).”
MicroRNA-125 family members exert a similar role in the regulation of murine hematopoiesis
Wojtowicz, E. E., Walasek, M. A., Broekhuis, M., Weersing, E., Ritsema, M., Ausema, A., Bystrykh, L. V., & de Haan, G. (2014) · Experimental Hematology · doi:10.1016/j.exphem.2014.06.010 · Cited by 32 · cited 17× · see citing works
“To study the function ofmiR-125a in humanHSPCs, we generated a lentiviral vector with miR-125a (miR-125OE) under a constitutive SFFV promoter using an orange fluorescent protein (OFP) reporter (Figure 1B).”
InfluentialSec-containing TrxR1 is essential for self-sufficiency of cells by control of glucose-derived H2O2
Peng, X., Mandal, P. K., Kaminskyy, V. O., Lindqvist, A., Conrad, M., & Arnér, E. S. J. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.209 · Cited by 29 · cited 1× · see citing works
“In addition, we identified interleukin-16 (IL-16) and Txnrd1, the latter gene playing a role in protection against oxidative stress (Peng et al., 2014).”
Aljurf, M. D., Rizzo, J. D., Mohty, M., Hussain, F., Madrigal, J. A., Pasquini, M. C., Passweg, J. R., Chaudhri, N. A., Ghavamzadeh, A., Solh, H. E., et al. (2014) · Bone Marrow Transplantation · doi:10.1038/bmt.2014.78 · Cited by 29 · cited 1× · see citing works
“…for malignant diseases such as leukemia, myelodysplasia, and myelofibrosis as well as non-malignant disorders such as severe aplastic anemia and congenital immune or enzyme deficiencies, Cell S with >40,000 transplants undertaken worldwide (Aljurf et al., 2014; Pineault and Abu-Khader, 2015).”
Umbilical cord blood transplantation: a maturing technology.
Oran, B., & Shpall, E. J. (2012) · PubMed · doi:10.1182/asheducation-2012.1.215 · Cited by 29 · cited 2× · see citing works
“Despite this success, 67% of patients who require allogeneic transplantation are not able to undergo this procedure due to the lack of matched donors (Oran and Shpall, 2012).”
A microRNA regulating adult hematopoietic stem cells
Guo, S., & Scadden, D. T. (2010) · Cell Cycle · doi:10.4161/cc.9.18.13174 · Cited by 9 · cited 11× · see citing works
“These observations are in line with previous reports inmurine HSPCs pointing to conservation of function across species (Gerrits et al., 2012; Guo and Scadden, 2010; O’Connell et al., 2010).”
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Aging of hematopoietic stem cells
de Haan, G., & Lazare, S. S. (2018) · Blood · doi:10.1182/blood-2017-06-746412 · Cited by 432 · see citing works
Spatially confined sub-tumor microenvironments in pancreatic cancer
Grünwald, B. T., Devisme, A., Andrieux, G., Vyas, F., Aliar, K., McCloskey, C. W., Macklin, A., Jang, G. H., Denroche, R., Romero, J. M., et al. (2021) · Cell · doi:10.1016/j.cell.2021.09.022 · Cited by 433 · see citing works
Cell Cycle Regulation of Stem Cells by MicroRNAs
Mens, M. M. J., & Ghanbari, M. (2018) · Stem Cell Reviews and Reports · doi:10.1007/s12015-018-9808-y · Cited by 220 · see citing works
MicroRNA-125 in immunity and cancer
Wang, J. K., Wang, Z., & Li, G. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.04.015 · Cited by 137 · see citing works
Jiang, Q., Isquith, J. M., Zipeto, M., Diep, R. H., Pham, J., Santos, N. P. D., Reynoso, E., Chau, J., Leu, H. S., Lazzari, E., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2018.11.017 · Cited by 99 · see citing works
“Advances in functional miRNA studies in hematological malignancies have provided an array of potential biomarkers and therapeutic targets for leukemia patients (Lechman et al., 2016; Wojtowicz et al., 2016).”
BackgroundPrincipe, S., Mejia‐Guerrero, S., Ignatchenko, V., Sinha, A., Ignatchenko, A., Shi, W., Pereira, K., Su, S., Huang, S. H., O’Sullivan, B., et al. (2018) · Journal of Proteome Research · doi:10.1021/acs.jproteome.7b00925 · Cited by 93 · see citing works
Transcriptomic classes of BCR-ABL1 lymphoblastic leukemia
Kim, J. C., Chan‐Seng‐Yue, M., Ge, S., Zeng, A. G. X., Ng, K., Gan, O. I., García‐Prat, L., Figueroa, E. F., Woo, T., Zhang, A. X. W., et al. (2023) · Nature Genetics · doi:10.1038/s41588-023-01429-4 · Cited by 57 · see citing works
Mammary molecular portraits reveal lineage-specific features and progenitor cell vulnerabilities
Casey, A. E., Sinha, A., Singhania, R., Livingstone, J. M., Waterhouse, P. D., Tharmapalan, P., Cruickshank, J., Shehata, M., Drysdale, E., Fang, H., et al. (2018) · The Journal of Cell Biology · doi:10.1083/jcb.201804042 · Cited by 53 · see citing works
“For proteins missing an LFQ value for one or more samples, LFQ intensities were replaced with median-adjusted intensity-based absolute quantification (iBAQ) values (Wojtowicz et al., 2016).”
MethodMammary epithelial cells have lineage-rooted metabolic identities
Mahendralingam, M. J., Kim, H., McCloskey, C. W., Aliar, K., Casey, A. E., Tharmapalan, P., Pellacani, D., Ignatchenko, V., García-Valero, M., Palomero, L., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00388-6 · Cited by 48 · see citing works
Targeting JNK pathway promotes human hematopoietic stem cell expansion
Xiao, X., Lai, W., Xie, H., Liu, Y., Guo, W., Liu, Y., Yu, L., Li, Y., Zhang, J. S., Chen, W., et al. (2019) · Cell Discovery · doi:10.1038/s41421-018-0072-8 · Cited by 50 · see citing works
Pan, Q., Liao, X., Liu, H., Wang, Y., Chen, Y., Zhao, B., Lazartigues, E. D., Yang, Y., & Ma, X. (2016) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00296.2016 · Cited by 46 · see citing works
Mutant CEBPA directly drives the expression of the targetable tumor-promoting factor CD73 in AML
Jakobsen, J. S., Laursen, L. G., Schuster, M. B., Pundhir, S., Schoof, E. M., Ge, Y. C., D’Altri, T., Vitting‐Seerup, K., Rapin, N., Gentil, C., et al. (2019) · Science Advances · doi:10.1126/sciadv.aaw4304 · Cited by 44 · see citing works
Taking One Step Back in Familial Hypercholesterolemia
Loaiza, N., Hartgers, M. L., Reeskamp, L. F., Balder, J.-W., Rimbert, A., Bazioti, V., Wolters, J. C., Winkelmeijer, M., Jansen, H., Dallinga‐Thie, G. M., et al. (2020) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.119.313470 · Cited by 43 · see citing works
Personalized genetics of the cholinergic blockade of neuroinflammation
Simchovitz, A., Heneka, M. T., & Soreq, H. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.13928 · Cited by 39 · see citing works
Quantitative Single-Cell Proteomics as a Tool to Characterize Cellular HierarchiesPreprint
Schoof, E. M., Furtwängler, B., Üresin, N., Rapin, N., Savickas, S., Gentil, C., Lechman, E. R., Keller, U. A. D., Dick, J. E., & Porse, B. T. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/745679 · Cited by 41 · see citing works
Qazi, M. A., Salim, S. K., Brown, K. R., Mikolajewicz, N., Savage, N. J., Han, H. R., Subapanditha, M., Bakhshinyan, D., Nixon, A. M. L., Vora, P., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111420 · Cited by 34 · see citing works
Tatari, N., Khan, S., Livingstone, J. M., Zhai, K., McKenna, D., Ignatchenko, V., Chokshi, C., Gwynne, W. D., Singh, M. P., Revill, S. D., et al. (2022) · Acta Neuropathologica · doi:10.1007/s00401-022-02506-4 · Cited by 32 · see citing works
“For proteins with missing LFQ values, median-adjusted iBAQ values were used as replacement [48].”
MethodFerreira, A. F., Călin, G. A., Picanço‐Castro, V., Kashima, S. H., Covas, D. T., & de Castro, F. A. (2018) · Journal of Cell Science · doi:10.1242/jcs.203018 · Cited by 31 · see citing works
“Altogether, the role of miR-125a, miR-125b, miR-155, miR-181, miR-221, miR-222, miR-223 in HSC self-renewal and differentiation has been extensively explored in in vitro experiments (Chen, 2004; Fazi et al., 2005; Felli et al., 2005; Shaham et al., 2012; Kozakowska, et al., 2014, Yao, 2016;Wojtowicz et al., 2016) (Fig.”
BackgroundInfluentialLeveraging the CSF proteome toward minimally-invasive diagnostics surveillance of brain malignancies
Mikolajewicz, N., Khan, S., Trifoi, M. D., Skakdoub, A., Ignatchenko, V., Mansouri, S., Zuccato, J., Zacharia, B. E., Glantz, M., Zadeh, G. M., et al. (2022) · Neuro-Oncology Advances · doi:10.1093/noajnl/vdac161 · Cited by 22 · see citing works
Rehn, M., Wenzel, A., Frank, A.-K., Schuster, M. B., Pundhir, S., Jørgensen, N., Vitting‐Seerup, K., Ge, Y. C., Jendholm, J., Michaut, M., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110793 · Cited by 23 · see citing works
The proteomic landscape of genotoxic stress-induced micronuclei
MacDonald, K. M., Khan, S., Lin, B., Hurren, R., Schimmer, A. D., Kislinger, T., & Harding, S. M. (2024) · Molecular Cell · doi:10.1016/j.molcel.2024.02.001 · Cited by 22 · see citing works
Pan, Q., Ma, C., Wang, Y., Wang, J., Zheng, J., Du, D., Liao, X., Chen, Y., Chen, Y., Bihl, J. C., et al. (2018) · Journal of Cellular Biochemistry · doi:10.1002/jcb.27581 · Cited by 18 · see citing works
“Our data were in agreement with previous studies showing that miR‐125a‐5p could promote EC angiogenesis,(20) and accelerate self‐renewal and long‐term multilineage repopulation of murine/human multipotent progenitors in transplanted recipient mice.(36) Third, we labeled the EMVs with PKH26 and analyzed the fluorescenc…”
ResultKrivdova, G., Voisin, V., Schoof, E. M., Marhon, S. A., Murison, A., McLeod, J. L., Gabra, M., Zeng, A. G. X., Aigner, S., Yee, B. A., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110481 · Cited by 16 · see citing works
Lee, S. C.-E. S., Pyo, A. H. A., Mohammadi, H., Zhang, J., Dvorkin‐Gheva, A., Malbeteau, L., Chung, S., Khan, S., Ciudad, M. T., Rondeau, V., et al. (2024) · Science Advances · doi:10.1126/sciadv.adq0355 · Cited by 16 · see citing works
Paolo, A. D., Farías, J., Garat, J., Macklin, A. M., Ignatchenko, V., Kislinger, T., & Sotelo-Silveira, J. R. (2021) · Journal of Proteome Research · doi:10.1021/acs.jproteome.0c00980 · Cited by 16 · see citing works
Piergentili, R., Marinelli, E., Cucinella, G., López, A., Napoletano, G., Gullo, G., & Zaami, S. (2024) · Non-Coding RNA · doi:10.3390/ncrna10020016 · Cited by 17 · see citing works
“…system, miR-125 regulates hematopoiesis, inflammation, and immune cell function. miR-125a controls stem cell homeostasis during hematopoiesis [135–138] and plays a role in immune cell identity [138]. miR-125-5p targeting IL-6R regulates macrophage inflammatory response and intestinal…”
MicroRNAs in hematopoietic stem cell aging
Luinenburg, D., & de Haan, G. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111281 · Cited by 13 · see citing works
Wojtowicz, E. E., Broekhuis, M., Weersing, E., Dinitzen, A. B., Verovskaya, E. V., Ausema, A., Ritsema, M., Zwart, E., de Haan, G., & Bystrykh, L. V. (2019) · Scientific Reports · doi:10.1038/s41598-019-38503-z · Cited by 13 · see citing works
Micro‐RNAs : A safety net to protect hematopoietic stem cell self‐renewal
Crisafulli, L., & Ficara, F. (2021) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1693 · Cited by 12 · see citing works
Huang, S., Tang, Z., Wang, Y., Chen, D., Li, J., Zhou, C., Lu, X., & Yuan, Y. (2020) · Epigenomics · doi:10.2217/epi-2019-0213 · Cited by 11 · see citing works
The miR-200c/141-ZEB2-TGFβ axis is aberrant in human T-cell prolymphocytic leukemia
Erkeland, S. J., Stavast, C. J., Schilperoord‐Vermeulen, J., Collo, G. D., van de Werken, H. J. G., León, L. G., van Hoven-Beijen, A., van Zuijen, I., Mueller, Y. M., Bindels, E. M., et al. (2021) · Haematologica · doi:10.3324/haematol.2020.263756 · Cited by 11 · see citing works
Understanding the “SMART” features of hematopoietic stem cells and beyond
Yuan, S., Sun, G., Zhang, Y., Dong, F., Cheng, H., & Cheng, T. (2021) · Science China Life Sciences · doi:10.1007/s11427-021-1961-1 · Cited by 11 · see citing works
YTHDC1-mediated microRNA maturation is essential for hematopoietic stem cells maintenance
Zuo, H., Liu, J., Shen, B., Sheng, Y., Ju, Z., & Wang, H. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-02203-z · Cited by 9 · see citing works
“The mice were housed in a speci fi c pathogen-free environment and provided with a standard diet.”
Specific Depletion of Leukemic Stem Cells: Can MicroRNAs Make the Difference?
Martiáñez, T., de Leeuw, D. C., Vermue, E., Ossenkoppele, G. J., & Smit, L. (2017) · Cancers · doi:10.3390/cancers9070074 · Cited by 8 · see citing works
“HSC Let-7 Hmg2a self-re ewal [61] miR-124 Tip110 differentiation [62] miR-125a BAK1 apoptosis [30,31,58]”
BackgroundInfluentialHueso, M., Cruzado, J. M., Torrás, J., & Navarro, E. (2019) · Genes · doi:10.3390/genes10010070 · Cited by 7 · see citing works
“Furthermore, miR-125a was recently described as a regulator of hemopoietic progenitor cell stemness [44].”
BackgroundMulti-Omics Study Reveals Nc886/vtRNA2-1 as a Positive Regulator of Prostate Cancer Cell Immunity
Oliveira‐Rizzo, C., Colantuono, C. L., Fernández-Álvarez, A. J., Boccaccio, G. L., Garat, B., Sotelo-Silveira, J. R., Khan, S., Ignatchenko, V., Lee, Y. S., Kislinger, T., et al. (2024) · Journal of Proteome Research · doi:10.1021/acs.jproteome.4c00521 · Cited by 6 · see citing works
Wenk, D., Ignatchenko, V., Macklin, A. M., Hübner, H., Gmeiner, P., Weikert, D., Pischetsrieder, M., & Kislinger, T. (2021) · Scientific Reports · doi:10.1038/s41598-021-83038-x · Cited by 6 · see citing works
Proteomic Response of Human Umbilical Vein Endothelial Cells to Histamine Stimulation
Emirbayer, P. E., Sinha, A., Ignatchenko, V., Hoyer, S., Dörrie, J., Schaft, N., Pischetsrieder, M., & Kislinger, T. (2017) · PROTEOMICS · doi:10.1002/pmic.201700116 · Cited by 6 · see citing works
Hoxb5 reprogrammes murine multipotent blood progenitors into haematopoietic stem cell‐like cells
Huang, D., Zhao, Q., Weng, Q., Zhang, Q., Wang, K., Liu, L., Xia, C., Wang, T., Xiong, J., Liu, X., et al. (2022) · Cell Proliferation · doi:10.1111/cpr.13235 · Cited by 4 · see citing works
Aastha, A., Wilding, H. E., Mikolajewicz, N., Khan, S., Ignatchenko, V., Filho, L. D. M., Bhanja, D., Remite-Berthet, G., Heebner, M., Glantz, M., et al. (2025) · Neuro-Oncology Advances · doi:10.1093/noajnl/vdaf046 · Cited by 4 · see citing works
Okeke, C., Silas, U., Nnodu, O., & Clementina, O. (2022) · Current Stem Cell Research & Therapy · doi:10.2174/1574888x17666220221104711 · Cited by 4 · see citing works
The Proteogenomics of Prostate Cancer Radioresistance
Haas, R., Frame, G., Khan, S., Neilsen, B. K., Hong, B. H., Yeo, C. P. X., Yamaguchi, T. N., Ong, E. H. W., Zhao, W., Carlin, B., et al. (2024) · Cancer Research Communications · doi:10.1158/2767-9764.crc-24-0292 · Cited by 3 · see citing works
“Missing LFQ values were replaced with median-adjusted iBAQ values (51).”
Luinenburg, D., Dinitzen, A. B., Svendsen, A. F., Cengiz, R., Ausema, A., Weersing, E., Bystrykh, L. V., & de Haan, G. (2020) · Experimental Hematology · doi:10.1016/j.exphem.2020.12.002 · Cited by 3 · see citing works
Dong, Y., Wang, K., Weng, Q., Wang, T., Zhou, P., Liu, X., Geng, Y., Liu, L., Wu, H., Wang, J., et al. (2020) · Cell Proliferation · doi:10.1111/cpr.12885 · Cited by 3 · see citing works
Hematopoietic Stem Cell Aging and Malignant Hemopathies
Goodhardt, M., Garrick, D., Dang, L., Salaroli, A., & Bron, D. (2017) · Springer eBooks · doi:10.1007/978-3-319-44870-1_71-1 · Cited by 2 · see citing works
Noncoding RNA and Epigenetic Change in Hematopoietic Stem Cell Aging
Garrick, D., David, A., Freitas, C., Djeghloul, D., & Goodhardt, M. (2019) · Springer eBooks · doi:10.1007/978-3-319-99375-1_99 · Cited by 2 · see citing works
Piergentili, R., Gullo, G., Cucinella, G., López, A., Napoletano, G., Marinelli, E., & Zaami, S. (2023) · Preprints.org · doi:10.20944/preprints202309.1713.v1 · Cited by 1 · see citing works
Loss of ING4 enhances hematopoietic regeneration in multipotent progenitor cells
Anderson, G. A., Hernandex, M., Alfaro-Quinde, C., Thompson, Z., Rodriguez, M., Binder, V., Taylor, A. M., & Kathrein, K. L. (2025) · PLoS ONE · doi:10.1371/journal.pone.0316256 · Cited by 1 · see citing works
“Finally, ectopic expression of miR-125a in murine and human multipotent progenitors also resulted in enhanced self-renewal and long-term multilineage engraftment following serial transplantation [43–46].”
miR-125b promotes leukemogenesis via VEGFA
Wong, T., & Link, D. C. (2017) · Blood · doi:10.1182/blood-2017-01-761544 · Cited by 1 · see citing works
“Indeed, expression of miR-125a confers long-term repopulating activity on human and mouse multipotent progenitors.(3) There is evidence implicating miR-125b in the pathogenesis of hematologic malignancies.”
BackgroundFrom the bedside to the bench: new discoveries on blood cell fate and function
Trompouki, E., Figueroa, E. F., Lucas, D., & Bowman, T. V. (2016) · Experimental Hematology · doi:10.1016/j.exphem.2016.11.007
Noncoding RNA and Epigenetic Change in Hematopoietic Stem Cell Aging
Garrick, D., David, A., Freitas, C., Djeghloul, D., & Goodhardt, M. (2017) · Springer eBooks · doi:10.1007/978-3-319-64597-1_99-1
MicroRNA-125a in Murine and Human Hematopoiesis
Luinenburg, D. (2021) · doi:10.33612/diss.180381414
Hoxb5 reprograms murine multipotent blood progenitors into hematopoietic stem cell-like cellsPreprint
Huang, D., Zhao, Q., Weng, Q., Zhang, Q., Wang, K., Liu, L., Xia, C., Wang, T., Xiong, J., Liu, X., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.10.25.465815
“Ectopic expression of miR-125a in mouse hematopoietic progenitors induced long-term hematopoiesis, but the recipient mice suffered an MPN-like disease after secondary transplantation (Gerrits et al., 2012; Wojtowicz et al., 2016; Wojtowicz et al., 2014).”
BackgroundHematopoietic Stem Cell Aging and Malignant Hemopathies
Goodhardt, M., Garrick, D., Dang, L., Salaroli, A., & Bron, D. (2020) · Springer eBooks · doi:10.1007/978-3-319-57415-8_71
Malouf, C., Duguid, A., Camiolo, G., Nitsche, L., Jakobczyk, H., Kotecha, R. S., Anderson, R. A., Barrett, N. A., Smith, O. P., & Ottersbach, K. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.01.12.523775
Rôle du long ARN non-codant CRNDE dans le myélome multiple
David, A. (2019) · theses.fr (ABES) · doi:10.70675/0a237555z2fe4z491bz9aefz7ccb14a7bb46
Malouf, C., Duguid, A., Vrenken, K. S., Leah, T., Medhi, R., Camiolo, G., Nitsche, L., Jakobczyk, H., Kotecha, R. S., Anderson, R. S., et al. (2026) · HemaSphere · doi:10.1002/hem3.70353
“21,52,53 miR ‐ 99 and miR ‐ 125 families can also drive skewing toward the myeloid lineage and contribute to the development of myeloid malignancies.”
Leucémies aiguës myéloïdes de l’adulte
Quessada, J., Dhia, L. B., Piazzola, P., Baccini, V., & Costello, R. T. (2026) · Encyclopédie médico-chirurgicale. Hématologie · doi:10.1016/s1155-1984(25)49084-0
Li, D., Zhou, R., Cheng, Z., Xu, H., Zhang, H., Li, X. G., Cao, L., & Li, F. (2026) · Journal of Translational Medicine · doi:10.1186/s12967-026-08544-w
“Some miRNAs, such as miR-126, miR-302 and miR-125, are associated with maintaining pluripotency and involved in maintenance of cancer stem cells [10–12].”
- Authors
- Wojtowicz, E. E., Lechman, E. R., Hermans, K. G., Schoof, E. M., Wienholds, E., Isserlin, R., van Veelen, P. A., Broekhuis, M. J. C., Janssen, G. M. C., Trotman-Grant, A., Dobson, S. M., Krivdova, G., Elzinga, J., Kennedy, J., Gan, O. I., Sinha, A., Ignatchenko, V., Kislinger, T., Dethmers-Ausema, B., Weersing, E., Alemdehy, M. F., de Looper, H. W. J., Bader, G. D., Ritsema, M., Erkeland, S. J., Bystrykh, L. V., Dick, J. E., & de Haan, G.
- Affiliations
- University Medical Center Groningen (NL)
- University Health Network (CA)
- University of Toronto (CA)
- Leiden University Medical Center (NL)
- Erasmus MC (NL)
- Corresponding author
- Dick, John E.
- ORCID
- Wojtowicz, Edyta E.
- Lechman, Eric R.
- Hermans, Karin G.
- Schoof, Erwin M.
- Isserlin, Ruth
- Broekhuis, Mathilde J.C.
- Janssen, George M.C.
- Trotman-Grant, Aaron
- Krivdova, Gabriela
- Sinha, Ankit
- Ignatchenko, Vladimir
- Kislinger, Thomas
- Alemdehy, Mir Farshid
- Bader, Gary D.
- Ritsema, Martha
- Erkeland, Stefan J.
- Bystrykh, Leonid V.
- Dick, John E.
- Venue
- Cell stem cell
- Publisher
- Elsevier BV
- Published
- 2016-09
- Volume
- 19
- Issue
- 3
- Pages
- 383-396
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC5500905
- OpenAlex
- W2462067774
- Cited by
- 60
- References
- 46
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 6 · 2023: 3 · 2022: 7 · 2021: 10 · 2020: 6 · 2019: 9 · 2018: 5 · 2017: 7 · 2016: 2
- FWCI
- 7.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
- PubMed Central (acceptedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- European Commission (264361, 609409, LTFCOFUND2013)
- Ministry of Earth Sciences
- Ministry of Education, India
- Universitair Medisch Centrum Groningen
- Canadian Institutes of Health Research
- National Human Genome Research Institute (R01HG009979, P41HG004118)
- National Institute of General Medical Sciences (R01GM070743, P41GM103504)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- miR-125a, microRNA, hematopoietic stem cells, multipotent progenitors, self-renewal, umbilical cord blood, HSC expansion, miRNA target genes, allogeneic stem cell transplantation, quantitative proteomics
- MeSH terms
- Cell Self Renewal, Animals, Gene Expression Regulation, Hematopoietic Stem Cells, Humans, Isotope Labeling, Male, Mice, Inbred C57BL, Models, Biological, Time Factors, Reproducibility of Results, Hematopoietic Stem Cell Transplantation, Antigens, CD34, MicroRNAs, Multipotent Stem Cells, Cell Proliferation, ADP-ribosyl Cyclase 1, Gene Regulatory Networks
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