Piwi genes are dispensable for normal hematopoiesis in mice.
Hematopoietic stem cells (HSC) must engage in a life-long balance between self-renewal and differentiation to sustain hematopoiesis. The highly conserved PIWI protein family regulates proliferative states of stem cells and their progeny in diverse organisms. A Human piwi gene (for clarity, the non-italicized "piwi" refers to the gene subfamily), HIWI (PIWIL1), is expressed in CD34⁺ stem/progenitor cells and transient expression of HIWI in a human leukemia cell line drastically reduces cell proliferation, implying the potential function of these proteins in hematopoiesis. Here, we report that one of the three piwi genes in mice, Miwi2 (Piwil4), is expressed in primitive hematopoetic cell types within the bone marrow. Mice with a global deletion of all three piwi genes, Miwi, Mili, and Miwi2, are able to maintain long-term hematopoiesis with no observable effect on the homeostatic HSC compartment in adult mice. The PIWI-deficient hematopoetic cells are capable of normal lineage reconstitution after competitive transplantation. We further show that the three piwi genes are dispensable during hematopoietic recovery after myeloablative stress by 5-FU. Collectively, our data suggest that the function of the piwi gene subfamily is not required for normal adult hematopoiesis.
Yale Stem Cell Center, Yale University School of Medicine, New Haven, Connecticut, United States of America ; Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
Mona J
MJ
Nolde
Ee-Chun
EC
Cheng
Shangqin
S
Guo
Haifan
H
Lin
D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout
D060565:Argonaute Proteins; C546575:PIWIL4 protein, mouse; C448522:Piwil1 protein, mouse; C448521:Piwil2 protein, mouse