ETV6 represses inflammatory response genes and regulates HSPC function during stress hematopoiesis in mice

Key Points • Germline heterozygosity for a thrombocytopenia 5–associated ETV6 variant impairs the repopulating capacity of mouse HSPCs.• In HSPCs, ETV6 binds to Tnf and other inflammatory gene loci and represses their expression during stress hematopoiesis.

[1]  Fabian J Theis,et al.  Best practices for single-cell analysis across modalities , 2023, Nature Reviews Genetics.

[2]  J. Cervera,et al.  The Clinical Spectrum, Diagnosis, and Management of GATA2 Deficiency , 2023, Cancers.

[3]  J. Klco,et al.  Mutant Samd9l expression impairs hematopoiesis and induces bone marrow failure in mice , 2022, The Journal of clinical investigation.

[4]  Luke Y. C. Chen,et al.  Inflammatory diseases in hematology: a review. , 2022, American journal of physiology. Cell physiology.

[5]  E. Pietras,et al.  Germline ETV6 mutation promotes inflammation and disrupts lymphoid development of early hematopoietic progenitors. , 2022, Experimental hematology.

[6]  T. Holland-Letz,et al.  Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging. , 2022, Cell stem cell.

[7]  Shondra M. Pruett-Miller,et al.  Activation of γ-globin gene expression by GATA1 and NF-Y in hereditary persistence of fetal hemoglobin , 2021, Nature Genetics.

[8]  J. Klco,et al.  Advances in germline predisposition to acute leukaemias and myeloid neoplasms , 2020, Nature Reviews Cancer.

[9]  Kenneth L. Jones,et al.  ETV6 germline mutations cause HDAC3/NCOR2 mislocalization and upregulation of interferon response genes , 2020, JCI insight.

[10]  M. Loh,et al.  Molecular Basis of ETV6-Mediated Predisposition to Childhood Acute Lymphoblastic Leukemia. , 2020, Blood.

[11]  G. Wertheim,et al.  Runx1 negatively regulates inflammatory cytokine production by neutrophils in response to Toll-like receptor signaling. , 2020, Blood advances.

[12]  E. Passegué,et al.  TNF-α Coordinates Hematopoietic Stem Cell Survival and Myeloid Regeneration. , 2019, Cell stem cell.

[13]  L. Calvi,et al.  Flaming and fanning: The Spectrum of inflammatory influences in myelodysplastic syndromes. , 2019, Blood reviews.

[14]  G. Hoser,et al.  Mobilization of Stem and Progenitor Cells in Septic Shock Patients , 2019, Scientific Reports.

[15]  D. Sinnett,et al.  Genome wide mapping of ETV6 binding sites in pre-B leukemic cells , 2018, Scientific Reports.

[16]  B. Reizis,et al.  Transcription factor Etv6 regulates functional differentiation of cross-presenting classical dendritic cells , 2018, The Journal of experimental medicine.

[17]  A. Fischer,et al.  Dominant‐negative IKZF1 mutations cause a T, B, and myeloid cell combined immunodeficiency , 2018, The Journal of clinical investigation.

[18]  Fabian J Theis,et al.  SCANPY: large-scale single-cell gene expression data analysis , 2018, Genome Biology.

[19]  S. Henikoff,et al.  Targeted in situ genome-wide profiling with high efficiency for low cell numbers , 2018, Nature Protocols.

[20]  Nicholas A. Sinnott-Armstrong,et al.  An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues , 2017, Nature Methods.

[21]  S. Miyano,et al.  Abnormal hematopoiesis and autoimmunity in human subjects with germline IKZF1 mutations , 2017, The Journal of allergy and clinical immunology.

[22]  W. Ouwehand,et al.  Germline variants in ETV6 underlie reduced platelet formation, platelet dysfunction and increased levels of circulating CD34+ progenitors , 2017, Haematologica.

[23]  Steven Henikoff,et al.  An efficient targeted nuclease strategy for high-resolution mapping of DNA binding sites , 2016, bioRxiv.

[24]  M. Suico,et al.  Roles and regulations of the ETS transcription factor ELF4/MEF , 2016, Journal of molecular cell biology.

[25]  Howard Y. Chang,et al.  Lineage-specific and single cell chromatin accessibility charts human hematopoiesis and leukemia evolution , 2016, Nature Genetics.

[26]  T. Kalina,et al.  Loss of B cells and their precursors is the most constant feature of GATA-2 deficiency in childhood myelodysplastic syndrome , 2016, Haematologica.

[27]  S. South,et al.  Loss of B Cells in Patients with Heterozygous Mutations in IKAROS. , 2016, The New England journal of medicine.

[28]  J. Klawitter,et al.  Aging-associated inflammation promotes selection for adaptive oncogenic events in B cell progenitors. , 2015, The Journal of clinical investigation.

[29]  Pui,et al.  Germline Genetic Variation in ETV6 and Risk of Childhood Acute Lymphoblastic Leukemia: a Systematic Genetic Study , 2015, The Lancet. Oncology.

[30]  Michael N. Edmonson,et al.  Germline ETV6 Mutations Confer Susceptibility to Acute Lymphoblastic Leukemia and Thrombocytopenia , 2015, PLoS genetics.

[31]  Christopher C. Porter,et al.  Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia , 2015, Nature Genetics.

[32]  David A. Williams,et al.  Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy , 2015, Nature Genetics.

[33]  Howard Y. Chang,et al.  ATAC‐seq: A Method for Assaying Chromatin Accessibility Genome‐Wide , 2015, Current protocols in molecular biology.

[34]  W. Bamlet,et al.  Inflammation-induced NFATc1-STAT3 transcription complex promotes pancreatic cancer initiation by KrasG12D. , 2014, Cancer discovery.

[35]  K. J. Henley,et al.  NLRP1 inflammasome activation induces pyroptosis of hematopoietic progenitor cells. , 2012, Immunity.

[36]  I. Weissman,et al.  CD47 Is Upregulated on Circulating Hematopoietic Stem Cells and Leukemia Cells to Avoid Phagocytosis , 2009, Cell.

[37]  K. Sakamoto,et al.  CREB is a critical regulator of normal hematopoiesis and leukemogenesis. , 2008, Blood.

[38]  S. Orkin,et al.  Tel/Etv6 is an essential and selective regulator of adult hematopoietic stem cell survival. , 2004, Genes & development.

[39]  L. Carlsson,et al.  Hematopoietic progenitor/stem cells immortalized by Lhx2 generate functional hematopoietic cells in vivo. , 2002, Blood.

[40]  G. Zhu,et al.  RELT, a new member of the tumor necrosis factor receptor superfamily, is selectively expressed in hematopoietic tissues and activates transcription factor NF-kappaB. , 2001, Blood.

[41]  D. Hickstein,et al.  The ETS family member Tel antagonizes the Fli-1 phenotype in hematopoietic cells. , 2000, Blood cells, molecules & diseases.

[42]  Y Fujiwara,et al.  The TEL/ETV6 gene is required specifically for hematopoiesis in the bone marrow. , 1998, Genes & development.

[43]  T. Golub,et al.  Yolk sac angiogenic defect and intra‐embryonic apoptosis in mice lacking the Ets‐related factor TEL , 1997, The EMBO journal.

[44]  D. Carvajal,et al.  Administration of recombinant interleukin-12 to mice suppresses hematopoiesis in the bone marrow but enhances hematopoiesis in the spleen. , 1995, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[45]  Stuart H. Orkin,et al.  Transcription Factors and Hematopoietic Development (*) , 1995, The Journal of Biological Chemistry.

[46]  Kenichi A. Tanaka,et al.  CLOT RETRACTION , 1952, Lancet.

[47]  J. Lingrel,et al.  Articles on similar topics can be found in the following Blood collections Gene Expression (1086 articles) , 2005 .