Amit I

References (3)

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 : 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 : Microglia development follows a stepwise program to regulate brain homeostasis - Matcovitch-Natan_2016_Science_353_aad8670
Author(s) : Matcovitch-Natan O , Winter DR , Giladi A , Vargas Aguilar S , Spinrad A , Sarrazin S , Ben-Yehuda H , David E , Zelada Gonzalez F , Perrin P , Keren-Shaul H , Gury M , Lara-Astaiso D , Thaiss CA , Cohen M , Bahar Halpern K , Baruch K , Deczkowska A , Lorenzo-Vivas E , Itzkovitz S , Elinav E , Sieweke MH , Schwartz M , Amit I
Ref : Science , 353 :aad8670 , 2016
Abstract : Microglia, the resident myeloid cells of the central nervous system, play important roles in life-long brain maintenance and in pathology. Despite their importance, their regulatory dynamics during brain development have not been fully elucidated. Using genome-wide chromatin and expression profiling coupled with single-cell transcriptomic analysis throughout development, we found that microglia undergo three temporal stages of development in synchrony with the brain--early, pre-, and adult microglia--which are under distinct regulatory circuits. Knockout of the gene encoding the adult microglia transcription factor MAFB and environmental perturbations, such as those affecting the microbiome or prenatal immune activation, led to disruption of developmental genes and immune response pathways. Together, our work identifies a stepwise microglia developmental program integrating immune response pathways that may be associated with several neurodevelopmental disorders.
ESTHER : Matcovitch-Natan_2016_Science_353_aad8670
PubMedSearch : Matcovitch-Natan_2016_Science_353_aad8670
PubMedID: 27338705