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Spontaneous generation of germline characteristics in mouse fibrosarcoma cells.

Ma Z, Hu Y, Jiang G, Hou J, Liu R, Lu Y, Liu C - Sci Rep (2012)

Bottom Line: In this study, we further showed that cells functioning as germline could be present in mouse fibrosarcoma cells (L929 cell line).Early germline-like cells spontaneously appeared in L929 cells and further differentiated into oocyte-like cells.These germline-like cells can, in turn, develop into blastocyst-like structures in vitro and cause teratocarcinomas in vivo, which is consistent with natural germ cells in function.

View Article: PubMed Central - PubMed

Affiliation: Department of Labratory Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040, China.

ABSTRACT
Germline/embryonic-specific genes have been found to be activated in somatic tumors. In this study, we further showed that cells functioning as germline could be present in mouse fibrosarcoma cells (L929 cell line). Early germline-like cells spontaneously appeared in L929 cells and further differentiated into oocyte-like cells. These germline-like cells can, in turn, develop into blastocyst-like structures in vitro and cause teratocarcinomas in vivo, which is consistent with natural germ cells in function. Generation of germline-like cells from somatic tumors might provide a novel way to understand why somatic cancer cells have strong features of embryonic/germline development. It is thought that the germline traits of tumors are associated with the central characteristics of malignancy, such as immortalization, invasion, migration and immune evasion. Therefore, germline-like cells in tumors might provide potential targets to tumor biology, diagnosis and therapy.

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Related in: MedlinePlus

Formation of structures resembling preimplantation embryos from oocyte-like cells.Cleavage stage-like embryos and blastocyst-like structures spontaneously generated in cultures (A-G). (a) Two-cell stage embryo-like structure. (b) Three-cell stage embryo-like structure. (c, d) Smaller blastocyst-like structures. (E-G) Bigger blastocyst-like structures. (h-j) Expression of Oct4 protein was detected in a six-cell stage embryo-like structure. (h) Phase contrast images of the embryo-like structure. (i) Oct4 staining. (j) DAPI staining. (k) Oct4/DAPI staining. (l-o) Expression of Sox2 protein was detected in a four-cell stage embryo-like structure. (l) Phase contrast images of the embryo-like cell. (m) Sox2 staining. (n) DAPI staining. (o) Sox2/DAPI staining. (p-s) Expression of SSEA1 protein was detected in an early embryo-like structure. (p) Phase contrast images of the embryo-like structure. (q) SSEA1 staining. (r) DAPI staining. (s) SSEA1/DAPI staining. (t-v) Expression of DAZL protein was detected in embryo-like structure. (t) Phase contrast images of the embryo-like structure. (u) DAZL staining. (v) DAZL/DAPI staining. (w-y) Expression of DAZL protein was detected in a blastocyst-like structure. (w) DAZL staining. (x) DAPI staining. (y) DAZL/DAPI staining. Scale bars = 10 μm in (a-g), 25 μm in (h-y).
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f4: Formation of structures resembling preimplantation embryos from oocyte-like cells.Cleavage stage-like embryos and blastocyst-like structures spontaneously generated in cultures (A-G). (a) Two-cell stage embryo-like structure. (b) Three-cell stage embryo-like structure. (c, d) Smaller blastocyst-like structures. (E-G) Bigger blastocyst-like structures. (h-j) Expression of Oct4 protein was detected in a six-cell stage embryo-like structure. (h) Phase contrast images of the embryo-like structure. (i) Oct4 staining. (j) DAPI staining. (k) Oct4/DAPI staining. (l-o) Expression of Sox2 protein was detected in a four-cell stage embryo-like structure. (l) Phase contrast images of the embryo-like cell. (m) Sox2 staining. (n) DAPI staining. (o) Sox2/DAPI staining. (p-s) Expression of SSEA1 protein was detected in an early embryo-like structure. (p) Phase contrast images of the embryo-like structure. (q) SSEA1 staining. (r) DAPI staining. (s) SSEA1/DAPI staining. (t-v) Expression of DAZL protein was detected in embryo-like structure. (t) Phase contrast images of the embryo-like structure. (u) DAZL staining. (v) DAZL/DAPI staining. (w-y) Expression of DAZL protein was detected in a blastocyst-like structure. (w) DAZL staining. (x) DAPI staining. (y) DAZL/DAPI staining. Scale bars = 10 μm in (a-g), 25 μm in (h-y).

Mentions: Approximately 20% of the oocyte-like cells did not further mature but underwent spontaneous activation to generate parthenogenetic embryo-like structures. Embryo-like structures at different developmental stage from two-cell stage to blastocyst stage (Figure 4a–g) were observed in cultures. The size of the blastocyst-like structures mostly varied between 20 and 25 μm in diameter (Figure 4a–d), which is consistent with their original oocyte-like cells. A zona pellucida membrane and polar bodies were not detected around the embryo-like structures. Immunocytochemistry staining for Oct4 (Figure 4h–k, Supplemental Fig. S1), Sox2 (Figure 4l–o), and SSEA1 (Figure 4p–s) further indicated that blastocyst-like structures is similar to early natural embryos132526. Consistent with mammalian embryo at very early stage, the expression and distribution of Oct4 protein (Figure 4h–k, Supplemental Fig. S1) was detected in cytoplasm and starts to localize in the nucleus2639. Immunocytochemistry showed that DAZL were detected in embryo-like structures, which is consistent with the report that DAZL protein (Figure 4t–y) is present in mouse preimplantation embryo31. Taken together, the results indicated that the oocyte-like cells might be activated spontaneously to develop into preimplantation embryo-like structures in culture.


Spontaneous generation of germline characteristics in mouse fibrosarcoma cells.

Ma Z, Hu Y, Jiang G, Hou J, Liu R, Lu Y, Liu C - Sci Rep (2012)

Formation of structures resembling preimplantation embryos from oocyte-like cells.Cleavage stage-like embryos and blastocyst-like structures spontaneously generated in cultures (A-G). (a) Two-cell stage embryo-like structure. (b) Three-cell stage embryo-like structure. (c, d) Smaller blastocyst-like structures. (E-G) Bigger blastocyst-like structures. (h-j) Expression of Oct4 protein was detected in a six-cell stage embryo-like structure. (h) Phase contrast images of the embryo-like structure. (i) Oct4 staining. (j) DAPI staining. (k) Oct4/DAPI staining. (l-o) Expression of Sox2 protein was detected in a four-cell stage embryo-like structure. (l) Phase contrast images of the embryo-like cell. (m) Sox2 staining. (n) DAPI staining. (o) Sox2/DAPI staining. (p-s) Expression of SSEA1 protein was detected in an early embryo-like structure. (p) Phase contrast images of the embryo-like structure. (q) SSEA1 staining. (r) DAPI staining. (s) SSEA1/DAPI staining. (t-v) Expression of DAZL protein was detected in embryo-like structure. (t) Phase contrast images of the embryo-like structure. (u) DAZL staining. (v) DAZL/DAPI staining. (w-y) Expression of DAZL protein was detected in a blastocyst-like structure. (w) DAZL staining. (x) DAPI staining. (y) DAZL/DAPI staining. Scale bars = 10 μm in (a-g), 25 μm in (h-y).
© Copyright Policy - open-access
Related In: Results  -  Collection

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f4: Formation of structures resembling preimplantation embryos from oocyte-like cells.Cleavage stage-like embryos and blastocyst-like structures spontaneously generated in cultures (A-G). (a) Two-cell stage embryo-like structure. (b) Three-cell stage embryo-like structure. (c, d) Smaller blastocyst-like structures. (E-G) Bigger blastocyst-like structures. (h-j) Expression of Oct4 protein was detected in a six-cell stage embryo-like structure. (h) Phase contrast images of the embryo-like structure. (i) Oct4 staining. (j) DAPI staining. (k) Oct4/DAPI staining. (l-o) Expression of Sox2 protein was detected in a four-cell stage embryo-like structure. (l) Phase contrast images of the embryo-like cell. (m) Sox2 staining. (n) DAPI staining. (o) Sox2/DAPI staining. (p-s) Expression of SSEA1 protein was detected in an early embryo-like structure. (p) Phase contrast images of the embryo-like structure. (q) SSEA1 staining. (r) DAPI staining. (s) SSEA1/DAPI staining. (t-v) Expression of DAZL protein was detected in embryo-like structure. (t) Phase contrast images of the embryo-like structure. (u) DAZL staining. (v) DAZL/DAPI staining. (w-y) Expression of DAZL protein was detected in a blastocyst-like structure. (w) DAZL staining. (x) DAPI staining. (y) DAZL/DAPI staining. Scale bars = 10 μm in (a-g), 25 μm in (h-y).
Mentions: Approximately 20% of the oocyte-like cells did not further mature but underwent spontaneous activation to generate parthenogenetic embryo-like structures. Embryo-like structures at different developmental stage from two-cell stage to blastocyst stage (Figure 4a–g) were observed in cultures. The size of the blastocyst-like structures mostly varied between 20 and 25 μm in diameter (Figure 4a–d), which is consistent with their original oocyte-like cells. A zona pellucida membrane and polar bodies were not detected around the embryo-like structures. Immunocytochemistry staining for Oct4 (Figure 4h–k, Supplemental Fig. S1), Sox2 (Figure 4l–o), and SSEA1 (Figure 4p–s) further indicated that blastocyst-like structures is similar to early natural embryos132526. Consistent with mammalian embryo at very early stage, the expression and distribution of Oct4 protein (Figure 4h–k, Supplemental Fig. S1) was detected in cytoplasm and starts to localize in the nucleus2639. Immunocytochemistry showed that DAZL were detected in embryo-like structures, which is consistent with the report that DAZL protein (Figure 4t–y) is present in mouse preimplantation embryo31. Taken together, the results indicated that the oocyte-like cells might be activated spontaneously to develop into preimplantation embryo-like structures in culture.

Bottom Line: In this study, we further showed that cells functioning as germline could be present in mouse fibrosarcoma cells (L929 cell line).Early germline-like cells spontaneously appeared in L929 cells and further differentiated into oocyte-like cells.These germline-like cells can, in turn, develop into blastocyst-like structures in vitro and cause teratocarcinomas in vivo, which is consistent with natural germ cells in function.

View Article: PubMed Central - PubMed

Affiliation: Department of Labratory Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040, China.

ABSTRACT
Germline/embryonic-specific genes have been found to be activated in somatic tumors. In this study, we further showed that cells functioning as germline could be present in mouse fibrosarcoma cells (L929 cell line). Early germline-like cells spontaneously appeared in L929 cells and further differentiated into oocyte-like cells. These germline-like cells can, in turn, develop into blastocyst-like structures in vitro and cause teratocarcinomas in vivo, which is consistent with natural germ cells in function. Generation of germline-like cells from somatic tumors might provide a novel way to understand why somatic cancer cells have strong features of embryonic/germline development. It is thought that the germline traits of tumors are associated with the central characteristics of malignancy, such as immortalization, invasion, migration and immune evasion. Therefore, germline-like cells in tumors might provide potential targets to tumor biology, diagnosis and therapy.

Show MeSH
Related in: MedlinePlus