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

PLoS One. 2013 Dec 23;8(12):e82573. doi: 10.1371/journal.pone.0082573. eCollection 2013.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / pathology
  • Animals
  • Argonaute Proteins / deficiency*
  • Argonaute Proteins / metabolism
  • Blood Cells / metabolism
  • Cell Differentiation*
  • Cell Line, Tumor
  • Gene Knockdown Techniques
  • Hematopoiesis*
  • Hemoglobins / metabolism
  • Leukemia, Erythroblastic, Acute / genetics
  • Leukemia, Erythroblastic, Acute / pathology*
  • Mice, Inbred C57BL
  • Organ Specificity / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • Sequence Analysis, RNA
  • Spleen / metabolism
  • Whole-Body Irradiation

Substances

  • Argonaute Proteins
  • Hemoglobins
  • PIWIL4 protein, mouse
  • RNA, Messenger
  • RNA, Small Interfering