Atypical protein kinase C (aPKCζ and aPKCλ) is dispensable for mammalian hematopoietic stem cell activity and blood formation

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 (aPKC zeta and aPKC lambda), 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 aPKC zeta or aPKC lambda or both in vivo. Mice, having constitutive and hematopoietic-specific (Vav1-Cre) deletion of aPKC zeta and aPKC lambda, respectively, have normal hematopoiesis, including normal HSC self-renewal, engraftment, differentiation, and interaction with the bone marrow microenvironment. Furthermore, inducible complete deletion of aPKC lambda (Mx1-Cre) in aPKC zeta(-/-) HSC does not affect HSC polarization, self-renewal, engraftment, or lineage repopulation. In addition, aPKC zeta- and aPKC lambda-deficient HSCs elicited a normal pattern of hematopoietic recovery secondary to myeloablative stress. Taken together, the expression of aPKC zeta, aPKC lambda, 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 aPKC zeta/lambda-directed cell polarity signaling mechanism in mammalian HSC fate determination.