Deficiency of MIWI2 (Piwil4) induces mouse erythroleukemia cell differentiation, but has no effect on hematopoiesis in vivo

• Published in: PloS one Vol. 8; no. 12; p. e82573
• Main Authors: Jacobs, James E, Wagner, Mark, Dhahbi, Joseph, Boffelli, Dario, Martin, David I K
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.12.2013; Public Library of Science (PLoS)
• Subjects: Abnormalities; Acids; Aging - pathology; Animal tissues; Animals; Argonaute Proteins - deficiency; Argonaute Proteins - metabolism; Blood Cells - metabolism; Cell cycle; Cell Differentiation; Cell Line, Tumor; Cell self-renewal; Children & youth; Defects; Differentiation (biology); DNA methylation; Drosophila; Erythroleukemia; Gene Knockdown Techniques; Genes; Genomes; Genomics; Germ cells; Hematopoiesis; Hematopoietic stem cells; Hemoglobins - metabolism; House mouse; Insects; Leukemia, Erythroblastic, Acute - genetics; Leukemia, Erythroblastic, Acute - pathology; Life span; Meiosis; Methylation; Mice; Mice, Inbred C57BL; mRNA; Non-coding RNA; Organ Specificity - genetics; Progenitor cells; Proteins; Ribonucleic acid; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Small Interfering - metabolism; Rodents; Sequence Analysis, RNA; Spermatogenesis; Spleen - metabolism; Statistical analysis; Stem cells; Studies; Whole-Body Irradiation; United States > US; California
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0082573

Piwi proteins and their small non-coding RNA partners are involved in the maintenance of stem cell character and genome integrity in the male germ cells of mammals. MIWI2, one of the mouse Piwi-like proteins, is expressed in the prepachytene phase of spermatogenesis during the period of de novo methylation. Absence of this protein leads to meiotic defects and a progressive loss of germ cells. There is an accumulation of evidence that Piwi proteins may be active in hematopoietic tissues. Thus, MIWI2 may have a role in hematopoietic stem and/or progenitor cell self-renewal and differentiation, and defects in MIWI2 may lead to abnormal hematopoiesis. MIWI2 mRNA can be detected in a mouse erythroblast cell line by RNA-seq, and shRNA-mediated knockdown of this mRNA causes the cells to take on characteristics of differentiated erythroid precursors. However, there are no detectable hematopoietic abnormalities in a MIWI2-deficient mouse model. While subtle, non-statistically significant changes were noted in the hematopoietic function of mice without a functional MIWI2 gene when compared to wild type mice, our results show that MIWI2 is not solely necessary for hematopoiesis within the normal life span of a mouse.