Mildner A

References (6)

Title : MicroRNA-142 controls thymocyte proliferation - Mildner_2017_Eur.J.Immunol_47_1142
Author(s) : Mildner A , Chapnik E , Varol D , Aychek T , Lampl N , Rivkin N , Bringmann A , Paul F , Boura-Halfon S , Hayoun YS , Barnett-Itzhaki Z , Amit I , Hornstein E , Jung S
Ref : European Journal of Immunology , 47 :1142 , 2017
Abstract : T-cell development is a spatially and temporally regulated process, orchestrated by well-defined contributions of transcription factors and cytokines. Here, we identify the noncoding RNA miR-142 as an additional regulatory layer within murine thymocyte development and proliferation. MiR-142 deficiency impairs the expression of cell cycle-promoting genes in mature mouse thymocytes and early progenitors, accompanied with increased levels of cyclin-dependent kinase inhibitor 1B (Cdkn1b, also known as p27(Kip1) ). By using CRISPR/Cas9 technology to delete the miR-142-3p recognition element in the 3'UTR of cdkn1b, we confirm that this gene is a novel target of miR-142-3p in vivo. Increased Cdkn1b protein expression alone however was insufficient to cause proliferation defects in thymocytes, indicating the existence of additional critical miR-142 targets. Collectively, we establish a key role for miR-142 in the control of early and mature thymocyte proliferation, demonstrating the multifaceted role of a single miRNA on several target genes.
ESTHER : Mildner_2017_Eur.J.Immunol_47_1142
PubMedSearch : Mildner_2017_Eur.J.Immunol_47_1142
PubMedID: 28471480

Title : Rac1 functions downstream of miR-142 in regulation of erythropoiesis -
Author(s) : Rivkin N , Chapnik E , Birger Y , Yanowski E , Curato C , Mildner A , Porat Z , Amir G , Izraeli S , Jung S , Hornstein E
Ref : Haematologica , 102 :e476 , 2017
PubMedID: 28912177

Title : Erythrocyte survival is controlled by microRNA-142 - Rivkin_2017_Haematologica_102_676
Author(s) : Rivkin N , Chapnik E , Mildner A , Barshtein G , Porat Z , Kartvelishvily E , Dadosh T , Birger Y , Amir G , Yedgar S , Izraeli S , Jung S , Hornstein E
Ref : Haematologica , 102 :676 , 2017
Abstract : Hematopoietic-specific microRNA-142 is a critical regulator of various blood cell lineages, but its role in erythrocytes is unexplored. Herein, we characterize the impact of microRNA-142 on erythrocyte physiology and molecular cell biology, using a mouse loss-of-function allele. We report that microRNA-142 is required for maintaining the typical erythrocyte biconcave shape and structural resilience, for the normal metabolism of reactive oxygen species, and for overall lifespan. microRNA-142 further controls ACTIN filament homeostasis and membrane skeleton organization. The analyses presented reveal previously unappreciated functions of microRNA-142 and contribute to an emerging view of small RNAs as key players in erythropoiesis. Finally, the work herein demonstrates how a housekeeping network of cytoskeletal regulators can be reshaped by a single micro-RNA denominator in a cell type specific manner.
ESTHER : Rivkin_2017_Haematologica_102_676
PubMedSearch : Rivkin_2017_Haematologica_102_676
PubMedID: 27909218

Title : Dicer Deficiency Differentially Impacts Microglia of the Developing and Adult Brain - Varol_2017_Immunity_46_1030
Author(s) : Varol D , Mildner A , Blank T , Shemer A , Barashi N , Yona S , David E , Boura-Halfon S , Segal-Hayoun Y , Chappell-Maor L , Keren-Shaul H , Leshkowitz D , Hornstein E , Fuhrmann M , Amit I , Maggio N , Prinz M , Jung S
Ref : Immunity , 46 :1030 , 2017
Abstract : Microglia seed the embryonic neuro-epithelium, expand and actively sculpt neuronal circuits in the developing central nervous system, but eventually adopt relative quiescence and ramified morphology in the adult. Here, we probed the impact of post-transcriptional control by microRNAs (miRNAs) on microglial performance during development and adulthood by generating mice lacking microglial Dicer expression at these distinct stages. Conditional Dicer ablation in adult microglia revealed that miRNAs were required to limit microglial responses to challenge. After peripheral endotoxin exposure, Dicer-deficient microglia expressed more pro-inflammatory cytokines than wild-type microglia and thereby compromised hippocampal neuronal functions. In contrast, prenatal Dicer ablation resulted in spontaneous microglia activation and revealed a role for Dicer in DNA repair and preservation of genome integrity. Accordingly, Dicer deficiency rendered otherwise radio-resistant microglia sensitive to gamma irradiation. Collectively, the differential impact of the Dicer ablation on microglia of the developing and adult brain highlights the changes these cells undergo with time.
ESTHER : Varol_2017_Immunity_46_1030
PubMedSearch : Varol_2017_Immunity_46_1030
PubMedID: 28636953

Title : miR-142 orchestrates a network of actin cytoskeleton regulators during megakaryopoiesis - Chapnik_2014_Elife_3_e01964
Author(s) : Chapnik E , Rivkin N , Mildner A , Beck G , Pasvolsky R , Metzl-Raz E , Birger Y , Amir G , Tirosh I , Porat Z , Israel LL , Lellouche E , Michaeli S , Lellouche JP , Izraeli S , Jung S , Hornstein E
Ref : Elife , 3 :e01964 , 2014
Abstract : Genome-encoded microRNAs (miRNAs) provide a posttranscriptional regulatory layer that controls the differentiation and function of various cellular systems, including hematopoietic cells. miR-142 is one of the most prevalently expressed miRNAs within the hematopoietic lineage. To address the in vivo functions of miR-142, we utilized a novel reporter and a loss-of-function mouse allele that we have recently generated. In this study, we show that miR-142 is broadly expressed in the adult hematopoietic system. Our data further reveal that miR-142 is critical for megakaryopoiesis. Genetic ablation of miR-142 caused impaired megakaryocyte maturation, inhibition of polyploidization, abnormal proplatelet formation, and thrombocytopenia. Finally, we characterized a network of miR-142-3p targets which collectively control actin filament homeostasis, thereby ensuring proper execution of actin-dependent proplatelet formation. Our study reveals a pivotal role for miR-142 activity in megakaryocyte maturation and function, and demonstrates a critical contribution of a single miRNA in orchestrating cytoskeletal dynamics and normal hemostasis.DOI:
ESTHER : Chapnik_2014_Elife_3_e01964
PubMedSearch : Chapnik_2014_Elife_3_e01964
PubMedID: 24859754

Title : Brummer lipase is an evolutionary conserved fat storage regulator in Drosophila - Gronke_2005_Cell.Metab_1_323
Author(s) : Gronke S , Mildner A , Fellert S , Tennagels N , Petry S , Muller G , Jackle H , Kuhnlein RP
Ref : Cell Metab , 1 :323 , 2005
Abstract : Energy homeostasis, a fundamental property of all organisms, depends on the ability to control the storage and mobilization of fat, mainly triacylglycerols (TAG), in special organs such as mammalian adipose tissue or the fat body of flies. Malregulation of energy homeostasis underlies the pathogenesis of obesity in mammals including human. We performed a screen to identify nutritionally regulated genes that control energy storage in the model organism Drosophila. The brummer (bmm) gene encodes the lipid storage droplet-associated TAG lipase Brummer, a homolog of human adipocyte triglyceride lipase (ATGL). Food deprivation or chronic bmm overexpression depletes organismal fat stores in vivo, whereas loss of bmm activity causes obesity in flies. Our study identifies a key factor of insect energy homeostasis control. Their evolutionary conservation suggests Brummer/ATGL family members to be implicated in human obesity and establishes a basis for modeling mechanistic and therapeutic aspects of this disease in the fly.
ESTHER : Gronke_2005_Cell.Metab_1_323
PubMedSearch : Gronke_2005_Cell.Metab_1_323
PubMedID: 16054079