Abstract
The protein c-CBL is a ubiquitin ligase. It catalyzes the last step of the transfer of ubiquitin to target proteins. Upon completion of polyubiquitination, the target proteins are degraded. Clinically, it is important that c-CBL is mutated in a subset of patients who develop myeloid malignancies, which are diseases of the hematopoietic stem or progenitor cells. c-CBL has also been shown to be expressed by human spermatogonia. The whole spermatogonial cell population possesses a subset that comprises also the spermatogonial stem cells. Based on these findings we hypothesized that c-CBL might be a general stem cell marker. To test this, we first validated the antibody using marmoset bone marrow and adult testis. In both tissues, the expected staining pattern was observed. Western blot analysis revealed only one band of the expected size. Then, we examined the expression of c-CBL in marmoset monkey embryonic stem (ES) cells, induced pluripotent stem (iPS) cells and adult stem cells. We found that c-CBL is strongly expressed in undifferentiated marmoset iPS cells and ES cells. However, adult stem cells in the gut and the stomach did not express c-CBL, indicating that c-CBL is not a general stem cell marker. In summary, c-CBL is strongly expressed in pluripotent stem cells of the marmoset monkey as well as in selected adult stem cell types. Future studies will define the function of c-CBL in pluripotent stem cells.
Highlights
It is well known that premeiotic germ cells and induced pluripotent stem cells share the expression of many pluripotency-associated factors in both rodents and primates
We have recently shown that marmoset monkey primordial germ cells (PGCs), which are the embryonic precursors of the gametes, express the key pluripotency factors OCT4A (POU5F1) and NANOG as well as SALL4 and LIN28 (Aeckerle et al, 2015), which are all expressed by pluripotent stem cells
3.1 Validation of the c-CBL antibody for the marmoset monkey c-CBL is involved in the development of myeloid malignancies (Katzav and Schmitz, 2015), which originate from the bone marrow
Summary
It is well known that premeiotic germ cells and induced pluripotent stem (iPS) cells share the expression of many pluripotency-associated factors in both rodents and primates. We have recently shown that marmoset monkey primordial germ cells (PGCs), which are the embryonic precursors of the gametes, express the key pluripotency factors OCT4A (POU5F1) and NANOG as well as SALL4 and LIN28 (Aeckerle et al, 2015), which are all expressed by pluripotent stem cells. The two latter ones are expressed in different populations of adult spermatogonia (Aeckerle et al, 2012; Eildermann et al, 2012). Spermatogonia are the premeiotic germ cells in the adult testis and comprise the spermatogonial stem cell population. Germ cells are in vivo physiologically unipotent, there is a considerable similarity between premeiotic germ cells and pluripotent stem cells with regard to their gene expression signature and, under experimental conditions, their developmental potential
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