Jmjd1c is dispensable for healthy adult hematopoiesis and Jak2V617F-driven myeloproliferative disease initiation in mice
| Autor: | Johannes Heinemann, Hans F. Staehle, Jonas S. Jutzi, Anne M. Omlor, Albert Gruender, Heike L. Pahl |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Embryology Jumonji Domain-Containing Histone Demethylases Physiology Hematologic Cancers and Related Disorders Gene Knockout Techniques Mice 0302 clinical medicine Medicine and Health Sciences Femur Musculoskeletal System Staining Mice Knockout Multidisciplinary biology food and beverages Cell Staining Animal Models Hematology Phenotype Body Fluids Haematopoiesis Leukemia Histone Blood Experimental Organism Systems Oncology 030220 oncology & carcinogenesis Knockout mouse Medicine Stem cell Anatomy Research Article Science Embryonic Development Mouse Models DNA construction Research and Analysis Methods 03 medical and health sciences Myeloproliferative Disorders Model Organisms Cell Line Tumor medicine Animals Humans Molecular Biology Techniques Molecular Biology Skeleton DNA manipulations Embryos Biology and Life Sciences Cancers and Neoplasms Janus Kinase 2 medicine.disease Exon Trapping Hematopoiesis Blood Counts 030104 developmental biology Specimen Preparation and Treatment Case-Control Studies Mutation biology.protein Cancer research Animal Studies Demethylase Developmental Biology Cloning |
| Zdroj: | PLoS ONE PLoS ONE, Vol 15, Iss 2, p e0228362 (2020) |
| ISSN: | 1932-6203 |
| Popis: | The histone demethylase JMJD1C is overexpressed in patients with myeloproliferative neoplasms (MPNs) and has been implicated in leukemic stem cell function of MLL-AF9 and HOXA9-driven leukemia. In the emerging field of histone demethylase inhibitors, JMJD1C therefore became a potential target. Depletion of Jmjd1c expression significantly reduced cytokine-independent growth in an MPN cell line, indicating a role for JMJD1C in MPN disease maintenance. Here, we investigated a potential role for the demethylase in MPN disease initiation. We introduced a Cre-inducible JAK2V617F mutation into Jmjd1c knockout mice. We show that Jmjd1c is dispensable, both for healthy hematopoiesis as well as for JAK2V617F-driven MPN disease initiation. Jmjd1c knockout mice did not show any significant changes in peripheral blood composition. Likewise, introduction of JAK2V617F into Jmjd1c-/- mice led to a similar MPN phenotype as JAK2V617F in a Jmjd1c wt background. This indicates that there is a difference between the role of JMJD1C in leukemic stem cells and in MPN. In the latter, JMJC domain-containing family members may serve redundant roles, compensating for the loss of individual proteins. |
| Databáze: | OpenAIRE |
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