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43 results on '"Krivdova, Gabriela"'

1. Adaptation to ex vivo culture reduces human hematopoietic stem cell activity independently of the cell cycle

Author

Johnson, Carys S., Williams, Matthew, Sham, Kendig, Belluschi, Serena, Ma, Wenjuan, Wang, Xiaonan, Lau, Winnie W. Y., Kaufmann, Kerstin B., Krivdova, Gabriela, Calderbank, Emily F., Mende, Nicole, McLeod, Jessica, Mantica, Giovanna, Li, Juan, Grey-Wilson, Charlotte, Drakopoulos, Michael, Basheer, Shaaezmeen, Sinha, Shubhankar, Diamanti, Evangelia, Basford, Christina, Wilson, Nicola K., Howe, Steven J., Dick, John E., Göttgens, Berthold, Green, Anthony R., Francis, Natalie, and Laurenti, Elisa

Published
2024
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2. Identification of the global miR-130a targetome reveals a role for TBL1XR1 in hematopoietic stem cell self-renewal and t(8;21) AML

Author

Krivdova, Gabriela, Voisin, Veronique, Schoof, Erwin M, Marhon, Sajid A, Murison, Alex, McLeod, Jessica L, Gabra, Martino M, Zeng, Andy GX, Aigner, Stefan, Yee, Brian A, Shishkin, Alexander A, Van Nostrand, Eric L, Hermans, Karin G, Trotman-Grant, Aaron C, Mbong, Nathan, Kennedy, James A, Gan, Olga I, Wagenblast, Elvin, De Carvalho, Daniel D, Salmena, Leonardo, Minden, Mark D, Bader, Gary D, Yeo, Gene W, Dick, John E, and Lechman, Eric R

Subjects
Biological Sciences, Cancer, Stem Cell Research - Nonembryonic - Non-Human, Regenerative Medicine, Rare Diseases, Stem Cell Research, Pediatric, Hematology, Stem Cell Research - Nonembryonic - Human, Biotechnology, Genetics, Pediatric Cancer, Childhood Leukemia, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Blood, Generic health relevance, Cell Line, Tumor, Cell Self Renewal, Hematopoietic Stem Cells, Humans, Leukemia, Myeloid, Acute, MicroRNAs, Receptors, Cytoplasmic and Nuclear, Repressor Proteins, 21) AML, AML1-ETO, TBL1XR1, acute myeloid leukemia, chimeric AGO2 eCLIP-seq, hematopoietic stem cell, microRNA, molecular network, self-renewal, stemness, t(8, Biochemistry and Cell Biology, Medical Physiology, Biological sciences
Abstract

Gene expression profiling and proteome analysis of normal and malignant hematopoietic stem cells (HSCs) point to shared core stemness properties. However, discordance between mRNA and protein signatures highlights an important role for post-transcriptional regulation by microRNAs (miRNAs) in governing this critical nexus. Here, we identify miR-130a as a regulator of HSC self-renewal and differentiation. Enforced expression of miR-130a impairs B lymphoid differentiation and expands long-term HSCs. Integration of protein mass spectrometry and chimeric AGO2 crosslinking and immunoprecipitation (CLIP) identifies TBL1XR1 as a primary miR-130a target, whose loss of function phenocopies miR-130a overexpression. Moreover, we report that miR-130a is highly expressed in t(8;21) acute myeloid leukemia (AML), where it is critical for maintaining the oncogenic molecular program mediated by the AML1-ETO complex. Our study establishes that identification of the comprehensive miRNA targetome within primary cells enables discovery of genes and molecular networks underpinning stemness properties of normal and leukemic cells.

Published
2022

4. TFEB-mediated endolysosomal activity controls human hematopoietic stem cell fate

Author

García-Prat, Laura, Kaufmann, Kerstin B., Schneiter, Florin, Voisin, Veronique, Murison, Alex, Chen, Jocelyn, Chan-Seng-Yue, Michelle, Gan, Olga I., McLeod, Jessica L., Smith, Sabrina A., Shoong, Michelle C., Parris, Darrien, Pan, Kristele, Zeng, Andy G.X., Krivdova, Gabriela, Gupta, Kinam, Takayanagi, Shin-Ichiro, Wagenblast, Elvin, Wang, Weijia, Lupien, Mathieu, Schroeder, Timm, Xie, Stephanie Z., and Dick, John E.

Published
2021
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5. A stemness screen reveals C3orf54/INKA1 as a promoter of human leukemia stem cell latency

Author

Kaufmann, Kerstin B., Garcia-Prat, Laura, Liu, Qiang, Ng, Stanley W.K., Takayanagi, Shin-Ichiro, Mitchell, Amanda, Wienholds, Erno, van Galen, Peter, Cumbaa, Christian A., Tsay, Mike J., Pastrello, Chiara, Wagenblast, Elvin, Krivdova, Gabriela, Minden, Mark D., Lechman, Eric R., Zandi, Sasan, Jurisica, Igor, Wang, Jean C.Y., Xie, Stephanie Z., and Dick, John E.

Published
2019
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6. Ectopic miR-125a Expression Induces Long-Term Repopulating Stem Cell Capacity in Mouse and Human Hematopoietic Progenitors

Author

Wojtowicz, Edyta E., Lechman, Eric R., Hermans, Karin G., Schoof, Erwin M., Wienholds, Erno, Isserlin, Ruth, van Veelen, Peter A., Broekhuis, Mathilde J.C., Janssen, George M.C., Trotman-Grant, Aaron, Dobson, Stephanie M., Krivdova, Gabriela, Elzinga, Jantje, Kennedy, James, Gan, Olga I., Sinha, Ankit, Ignatchenko, Vladimir, Kislinger, Thomas, Dethmers-Ausema, Bertien, Weersing, Ellen, Alemdehy, Mir Farshid, de Looper, Hans W.J., Bader, Gary D., Ritsema, Martha, Erkeland, Stefan J., Bystrykh, Leonid V., Dick, John E., and de Haan, Gerald

Published
2016
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7. miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells

Author

Lechman, Eric R., Gentner, Bernhard, Ng, Stanley W.K., Schoof, Erwin M., van Galen, Peter, Kennedy, James A., Nucera, Silvia, Ciceri, Fabio, Kaufmann, Kerstin B., Takayama, Naoya, Dobson, Stephanie M., Trotman-Grant, Aaron, Krivdova, Gabriela, Elzinga, Janneke, Mitchell, Amanda, Nilsson, Björn, Hermans, Karin G., Eppert, Kolja, Marke, Rene, Isserlin, Ruth, Voisin, Veronique, Bader, Gary D., Zandstra, Peter W., Golub, Todd R., Ebert, Benjamin L., Lu, Jun, Minden, Mark, Wang, Jean C.Y., Naldini, Luigi, and Dick, John E.

Published
2016
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9. Adaptation toex vivoculture drives human haematopoietic stem cell loss of repopulation capacity in a cell cycle independent manner

Author

Johnson, Carys S., primary, Sham, Kendig, additional, Belluschi, Serena, additional, Wang, Xiaonan, additional, Lau, Winnie, additional, Kaufmann, Kerstin B., additional, Krivdova, Gabriela, additional, Calderbank, Emily F., additional, Mende, Nicole, additional, McLeod, Jessica, additional, Mantica, Giovanna, additional, Williams, Matthew J., additional, Grey-Wilson, Charlotte, additional, Drakopoulos, Michael, additional, Sinha, Shubhankar, additional, Diamanti, Evangelia, additional, Basford, Christina, additional, Green, Anthony R., additional, Wilson, Nicola K., additional, Howe, Steven J., additional, Dick, John E., additional, Göttgens, Bertie, additional, Francis, Natalie, additional, and Laurenti, Elisa, additional

Published
2022
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10. Identification of Global miRNA Targetomes within Human Hematopoietic Progenitors and Acute Myeloid Leukemia Uncovers Unique Molecular Networks Centered on Mitochondria Function in Leukemic Stem Cells

Author

Krivdova, Gabriela, primary, Yee, Brian, additional, Aigner, Stefan, additional, Gabra, Martino, additional, Shishkin, Alexander, additional, Nguyen, Long, additional, McLeod, Jessica L, additional, Carley, Leah, additional, Salmena, Leonardo, additional, Shakib, Lorien, additional, Minden, Mark D., additional, Van Nostrand, Eric L, additional, Yeo, Gene W., additional, Lechman, Eric R., additional, and Dick, John E., additional

Published
2022
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15. Dichotomous regulation of lysosomes by MYC and TFEB controls hematopoietic stem cell fate

Author

García-Prat, Laura, Kaufmann, Kerstin B., Schneiter, Florin, Voisin, Veronique, Murison, Alex, Chen, Jocelyn, Chan-Seng-Yue, Michelle, Gan, Olga I., McLeod, Jessica L., Smith, Sabrina A., Shoong, Michelle C., Paris, Darrien, Pan, Kristele, Zeng, Andy G.X., Krivdova, Gabriela, Gupta, Kinam, Takayanagi, Shin-Ichiro, Wagenblast, Elvin, Wang, Weijia, Lupien, Mathieu, Schroeder, Timm, Xie, Stephanie Z., and Dick, John E.

Subjects
Myelopoiesis, TFEB, TfR1, Anabolism, Long-term HSC, Self-renewal, Catabolism, Erythropoiesis, MYC, Lysosomes
Abstract

It is critical to understand how quiescent long-term hematopoietic stem cells (LT-HSC) sense demand from daily and stress-mediated cues and transition into bioenergetically active progeny to differentiate and meet these cellular needs. Here, we show that lysosomes, which are sophisticated nutrient sensing and signaling centers, are dichotomously regulated by the Transcription Factor EB (TFEB) and MYC to balance catabolic and anabolic processes required for activating LT-HSC and guiding their lineage fate. TFEB-mediated induction of the endolysosomal pathway causes membrane receptor degradation, limiting LT-HSC metabolic and mitogenic activation, which promotes quiescence, self-renewal and governs erythroid-myeloid commitment. By contrast, MYC engages biosynthetic processes while repressing lysosomal catabolism to drive LT-HSC activation. Collectively, our study identifies lysosomes as a central regulatory hub for proper and coordinated stem cell fate determination., bioRxiv

Published
2021
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16. 2029 – TFEB-MEDIATED ENDO-LYSOSOMAL ACTIVITY CONTROLS HEMATOPOIETIC STEM CELL FATE

Author

Prat, Laura Garcia, primary, Kaufmann, Kerstin, additional, Schneiter, Florin, additional, Voisin, Veronique, additional, Murison, Alex, additional, Chen, Jocelyn, additional, Chan-Seng-Yue, Michelle, additional, McLeod, Jessica, additional, Gan, Olga, additional, Smith, Sabrina, additional, Shoong, Michelle, additional, Parris, Darrien, additional, Pan, Kristele, additional, Zeng, Andy G, additional, Krivdova, Gabriela, additional, Gupta, Kinam, additional, Takayanagi, Shin-Ichiro, additional, Wagenblast, Elvin, additional, Wang, Weija, additional, Lupien, Mathieu, additional, Schroeder, Timm, additional, Xie, Stephanie, additional, and Dick, John, additional

Published
2021
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17. Identification of the Global miR-130a Targetome Reveals a Novel Role for TBL1XR1 in Hematopoietic Stem Cell Self-Renewal and t(8;21) AML

Author

Krivdova, Gabriela, primary, Voisin, Veronique, additional, Schoof, Erwin M, additional, Marhon, Sajid A, additional, Murison, Alex, additional, McLeod, Jessica L, additional, Gabra, Martino, additional, Zeng, Andy GX, additional, Van Nostrand, Eric L, additional, Aigner, Stefan, additional, Shishkin, Alexander A, additional, Yee, Brian A, additional, Hermans, Karin G, additional, Trotman-Grant, Aaron G, additional, Mbong, Nathan, additional, Kennedy, James A, additional, Gan, Olga I, additional, Wagenblast, Elvin, additional, De Carvalho, Daniel D, additional, Salmena, Leonardo, additional, Minden, Mark D, additional, Bader, Gary D, additional, Yeo, Gene W, additional, Dick, John E, additional, and Lechman, Eric R, additional

Published
2021
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18. Mapping the cellular origin and early evolution of leukemia in Down syndrome

Author

Wagenblast, Elvin, primary, Araújo, Joana, additional, Gan, Olga I., additional, Cutting, Sarah K., additional, Murison, Alex, additional, Krivdova, Gabriela, additional, Azkanaz, Maria, additional, McLeod, Jessica L., additional, Smith, Sabrina A., additional, Gratton, Blaise A., additional, Marhon, Sajid A., additional, Gabra, Martino, additional, Medeiros, Jessie J. F., additional, Manteghi, Sanaz, additional, Chen, Jian, additional, Chan-Seng-Yue, Michelle, additional, Garcia-Prat, Laura, additional, Salmena, Leonardo, additional, De Carvalho, Daniel D., additional, Abelson, Sagi, additional, Abdelhaleem, Mohamed, additional, Chong, Karen, additional, Roifman, Maian, additional, Shannon, Patrick, additional, Wang, Jean C. Y., additional, Hitzler, Johann K., additional, Chitayat, David, additional, Dick, John E., additional, and Lechman, Eric R., additional

Published
2021
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19. Dichotomous regulation of lysosomes by MYC and TFEB controls hematopoietic stem cell fate

Author

García-Prat, Laura, primary, Kaufmann, Kerstin B., additional, Schneiter, Florin, additional, Voisin, Veronique, additional, Murison, Alex, additional, Chen, Jocelyn, additional, Chan-Seng-Yue, Michelle, additional, Gan, Olga I., additional, McLeod, Jessica L., additional, Smith, Sabrina A., additional, Shoong, Michelle C., additional, Paris, Darrien, additional, Pan, Kristele, additional, Zeng, Andy G.X., additional, Krivdova, Gabriela, additional, Gupta, Kinam, additional, Takayanagi, Shin-Ichiro, additional, Wagenblast, Elvin, additional, Wang, Weijia, additional, Lupien, Mathieu, additional, Schroeder, Timm, additional, Xie, Stephanie Z., additional, and Dick, John E., additional

Published
2021
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20. Mapping the Cellular Origin and Early Evolution of Leukemia in Down Syndrome

Author

Wagenblast, Elvin, primary, Araújo, Joana, additional, Gan, Olga I., additional, Cutting, Sarah K., additional, Murison, Alex, additional, Krivdova, Gabriela, additional, Azkanaz, Maria, additional, McLeod, Jessica L., additional, Smith, Sabrina A., additional, Marhon, Sajid A, additional, Gabra, Martino, additional, Chan-Seng-Yue, Michelle, additional, Garcia-Prat, Laura, additional, Salmena, Leonardo, additional, De Carvalho, Daniel D, additional, Chong, Karen, additional, Roifman, Maian, additional, Shannon, Patrick, additional, Wang, Jean C Y, additional, Hitzler, Johann K., additional, Chitayat, David, additional, Dick, John E., additional, and Lechman, Eric R., additional

Published
2020
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23. A Human Model of Down Syndrome Associated Leukemia Reveals Different Cell of Origins for Initiation and Progression

Author

Wagenblast, Elvin, primary, Araújo, Joana, additional, Gan, Olga I., additional, Cutting, Sarah K, additional, Murison, Alex, additional, McLeod, Jessica L., additional, Krivdova, Gabriela, additional, Azkanaz, Maria, additional, Smith, Sabrina A, additional, Hitzler, Johann K, additional, Dick, John E., additional, and Lechman, Eric R, additional

Published
2020
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27. Understanding Pre-Leukemia in Trisomy 21 Human HSC and Modeling Progression Towards Down Syndrome Associated Leukemia Using CRISPR/Cas9 at Single Cell Resolution

Author

Wagenblast, Elvin, primary, Gan, Olga I., additional, Azkanaz, Maria, additional, Smith, Sabrina A., additional, Araújo, Joana, additional, Shakib, Lorien, additional, McLeod, Jessica L., additional, Krivdova, Gabriela, additional, Hitzler, Johann K., additional, Lechman, Eric R., additional, and Dick, John E., additional

Published
2019
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29. MiR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells [Cancer Cell 29, (2016) 214-228; February 8]

Author

Lechman, Eric R., Gentner, Bernhard, Ng, Stanley W. K., Schoof, Erwin M., van Galen, Peter, Kennedy, James A., Nucera, Silvia, Kaufmann, Kerstin B., Takayama, Naoya, Dobson, Stephanie M., Trotman Grant, Aaron, Krivdova, Gabriela, Elzinga, Janneke, Mitchell, Amanda, Nilsson, Björn, Hermans, Karin G., Eppert, Kolja, Marke, Rene, Isserlin, Ruth, Voisin, Veronique, Bader, Gary D., Zandstra, Peter W., Golub, Todd R., Ebert, Benjamin L., Lu, Jun, Minden, Mark, Wang, Jean C. Y., Dick, John E., CICERI, FABIO, NALDINI, LUIGI, Lechman, Eric R., Gentner, Bernhard, Ng, Stanley W. K., Schoof, Erwin M., van Galen, Peter, Kennedy, James A., Nucera, Silvia, Ciceri, Fabio, Kaufmann, Kerstin B., Takayama, Naoya, Dobson, Stephanie M., Trotman Grant, Aaron, Krivdova, Gabriela, Elzinga, Janneke, Mitchell, Amanda, Nilsson, Björn, Hermans, Karin G., Eppert, Kolja, Marke, Rene, Isserlin, Ruth, Voisin, Veronique, Bader, Gary D., Zandstra, Peter W., Golub, Todd R., Ebert, Benjamin L., Lu, Jun, Minden, Mark, Wang, Jean C. Y., Naldini, Luigi, and Dick, John E.

Subjects
Cancer Research, Oncology, Cell Biology
Published
2016

31. Microrna-130a Regulates Hematopoietic Stem Cell Self-Renewal By Repressing Chromatin Modifiers and Shaping the Accessible Chromatin Landscape

Author

Krivdova, Gabriela, primary, Erwin, Schoof E, additional, Voisin, Veronique, additional, Murison, Alex, additional, Hermans, Karin G., additional, Garcia Prat, Laura, additional, Gan, Olga I., additional, Wagenblast, Elvin, additional, Trotman-Grant, Aaron, additional, Lechman,, Eric R., additional, Minden, Mark D., additional, and Dick, John E., additional

Published
2018
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39. A stemness screen reveals C3orf54/INKA1as a promoter of human leukemia stem cell latency

Author

Kaufmann, Kerstin B., Garcia-Prat, Laura, Liu, Qiang, Ng, Stanley W.K., Takayanagi, Shin-Ichiro, Mitchell, Amanda, Wienholds, Erno, van Galen, Peter, Cumbaa, Christian A., Tsay, Mike J., Pastrello, Chiara, Wagenblast, Elvin, Krivdova, Gabriela, Minden, Mark D., Lechman, Eric R., Zandi, Sasan, Jurisica, Igor, Wang, Jean C.Y., Xie, Stephanie Z., and Dick, John E.

Abstract

There is a growing body of evidence that the molecular properties of leukemia stem cells (LSCs) are associated with clinical outcomes in acute myeloid leukemia (AML), and LSCs have been linked to therapy failure and relapse. Thus, a better understanding of the molecular mechanisms that contribute to the persistence and regenerative potential of LSCs is expected to result in the development of more effective therapies. We therefore interrogated functionally validated data sets of LSC-specific genes together with their known protein interactors and selected 64 candidates for a competitive in vivo gain-of-function screen to identify genes that enhanced stemness in human cord blood hematopoietic stem and progenitor cells. A consistent effect observed for the top hits was the ability to restrain early repopulation kinetics while preserving regenerative potential. Overexpression (OE) of the most promising candidate, the orphan gene C3orf54/INKA1, in a patient-derived AML model (8227) promoted the retention of LSCs in a primitive state manifested by relative expansion of CD34+cells, accumulation of cells in G0, and reduced output of differentiated progeny. Despite delayed early repopulation, at later times, INKA1-OE resulted in the expansion of self-renewing LSCs. In contrast, INKA1silencing in primary AML reduced regenerative potential. Mechanistically, our multidimensional confocal analysis found that INKA1regulates G0exit by interfering with nuclear localization of its target PAK4, with concomitant reduction of global H4K16ac levels. These data identify INKA1as a novel regulator of LSC latency and reveal a link between the regulation of stem cell kinetics and pool size during regeneration.

Published
2019
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42. A small RNA targets pokeweed antiviral protein transcript.

Author

Klenov, Alexander, Neller, Kira C. M., Burns, Lydia A., Krivdova, Gabriela, and Hudak, Katalin A.

Subjects
DISEASE resistance of plants, RIBOSOME-inactivating proteins, NON-coding RNA, ANTIVIRAL agents, POKEWEED, GENETIC transcription in plants
Abstract

Ribosome-inactivating proteins (RIPs) are a class of plant defense proteins with N-glycosidase activity (EC 3.2.2.22). Pokeweed antiviral protein (PAP) is a Type I RIP isolated from the pokeweed plant, Phytolacca americana, thought to confer broad-spectrum virus resistance in this plant. Through a combination of standard molecular techniques and RNA sequencing analysis, we report here that a small RNA binds and cleaves the open reading frame of PAP mRNA. Additionally, sRNA targeting of PAP is dependent on jasmonic acid (JA), a plant hormone important for defense against pathogen infection and herbivory. Levels of small RNA increased with JA treatment, as did levels of PAP mRNA and protein, suggesting that the small RNA functions to moderate the expression of PAP in response to this hormone. The association between JA and PAP expression, mediated by sRNA299, situates PAP within a signaling pathway initiated by biotic stress. The consensus sequence of sRNA299 was obtained through bioinformatic analysis of pokeweed small RNA sequencing. To our knowledge, this is the first account of a sRNA targeting a RIP gene. [ABSTRACT FROM AUTHOR]

Published
2016
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43. PLAG1 dampens protein synthesis to promote human hematopoietic stem cell self-renewal

Author

Chahi, Ava Keyvani, Belew, Muluken S., Xu, Joshua, Chen, He Tian Tony, Rentas, Stefan, Voisin, Veronique, Krivdova, Gabriela, Lechman, Eric, Marhon, Sajid A., De Carvalho, Daniel D., Dick, John E., Bader, Gary D., and Hope, Kristin J.

Abstract

Hematopoietic stem cell (HSC) dormancy is understood as supportive of HSC function and their long-term integrity. While regulation of stress responses incurred as a result of HSC activation is recognized as important in maintaining stem cell function, little is understood of the preventative machinery present in human HSCs that may serve to resist their activation and promote HSC self-renewal. We demonstrate that the transcription factor PLAG1 is essential for long-term HSC function and when overexpressed endows a 15.6-fold enhancement in the frequency of functional HSC in stimulatory conditions. Genome-wide measures of chromatin occupancy and PLAG1-directed gene expression changes combined with functional measures reveal that PLAG1 dampens protein synthesis, restrains cell growth and division, and enhances survival, with the primitive cell advantages it imparts being attenuated by addition of the potent translation activator, c-MYC. We find PLAG1 capitalizes on multiple regulatory factors to ensure protective diminished protein synthesis including 4EBP1 and translation-targeting miR-127, and does so independently of stress response signaling. Overall, our study identifies PLAG1 as an enforcer of human HSC dormancy and self-renewal through its highly context-specific regulation of protein biosynthesis, and classifies PLAG1 among a rare set of bona fideregulators of mRNA translation in these cells. Our findings showcase the importance of regulated translation control underlying human HSC physiology, its dysregulation under activating demands, and the potential if its targeting for therapeutic benefit.

Published
2022
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