Atypical protein kinase C (aPKCzeta and aPKClambda) is dispensable for mammalian hematopoietic stem cell activity and blood formation.

TitleAtypical protein kinase C (aPKCzeta and aPKClambda) is dispensable for mammalian hematopoietic stem cell activity and blood formation.
Publication TypeJournal Article
Year of Publication2011
AuthorsSengupta A, Duran A, Ishikawa E, Florian MCarolina, Dunn SK, Ficker AM, Leitges M, Geiger H, Diaz-Meco M, Moscat J, Cancelas JA
JournalProc Natl Acad Sci U S A
Volume108
Issue24
Pagination9957-62
Date Published2011 Jun 14
ISSN1091-6490
KeywordsAnimals, Cell Differentiation, Cell Lineage, Cell Polarity, Cell Proliferation, Female, Flow Cytometry, Gene Expression, Hematopoiesis, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells, Isoenzymes, Male, Mice, Mice, Inbred Strains, Mice, Knockout, Mice, Transgenic, Protein Kinase C, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction
Abstract

The stem-cell pool is considered to be maintained by a balance between symmetric and asymmetric division of stem cells. The cell polarity model proposes that the facultative use of symmetric and asymmetric cell division is orchestrated by a polarity complex consisting of partitioning-defective proteins Par3 and Par6, and atypical protein kinase C (aPKCζ and aPKCλ), which regulates planar symmetry of dividing stem cells with respect to the signaling microenvironment. However, the role of the polarity complex is unexplored in mammalian adult stem-cell functions. Here we report that, in contrast to accepted paradigms, polarization and activity of adult hematopoietic stem cell (HSC) do not depend on either aPKCζ or aPKCλ or both in vivo. Mice, having constitutive and hematopoietic-specific (Vav1-Cre) deletion of aPKCζ and aPKCλ, respectively, have normal hematopoiesis, including normal HSC self-renewal, engraftment, differentiation, and interaction with the bone marrow microenvironment. Furthermore, inducible complete deletion of aPKCλ (Mx1-Cre) in aPKCζ(-/-) HSC does not affect HSC polarization, self-renewal, engraftment, or lineage repopulation. In addition, aPKCζ- and aPKCλ-deficient HSCs elicited a normal pattern of hematopoietic recovery secondary to myeloablative stress. Taken together, the expression of aPKCζ, aPKCλ, or both are dispensable for primitive and adult HSC fate determination in steady-state and stress hematopoiesis, contrary to the hypothesis of a unique, evolutionary conserved aPKCζ/λ-directed cell polarity signaling mechanism in mammalian HSC fate determination.

DOI10.1073/pnas.1103132108
Alternate JournalProc Natl Acad Sci U S A
PubMed ID21653884
Grant ListR01-CA134530 / CA / NCI NIH HHS / United States
/ CRUK_ / Cancer Research UK / United Kingdom
R01-AI072581 / AI / NIAID NIH HHS / United States
R01-CA132847 / CA / NCI NIH HHS / United States
R01-HL087159 / HL / NHLBI NIH HHS / United States
Related Faculty: 
Jorge Moscat, Ph.D. Maria Diaz-Meco Conde, Ph.D.

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