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Somatic, Germ and Stem cells

Distinctions between somatic and germ cells. Establishment of somatic cell types. Establishment of the germ line. Fundamental differences in germ cell establishment between organisms. Where stem cells fit in…. Somatic, Germ and Stem cells. Two basic classes of cells in animals somatic cells

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Somatic, Germ and Stem cells

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  1. Distinctions between somatic and germ cells. Establishment of somatic cell types. Establishment of the germ line. Fundamental differences in germ cell establishment between organisms. Where stem cells fit in…. Somatic, Germ and Stem cells

  2. Two basic classes of cells in animals somatic cells germ cells Cell types Somatic cells - almost everything we see and use, skin, muscle, blood, etc. Germ cells - the cells that are responsible for reproduction, propagation of the species. Stem cell - neither fish nor fowl. Can in some cases do both.

  3. Germ vs. Somatic cells 1) These two classes of cells are established in different ways during development. 2) There are two fundamentally different processes by which germ cells are generated in different organisms.

  4. Establishment of somatic cells

  5. Gastrulation generates the three classes of somatic cells

  6. Ectoderm (outside) Endoderm (inside) Mesoderm (in between) frequently called the 3 germ layers Three classes of somatic cells

  7. Two different ways in different organisms 1) Preformation (segregation) 2) Epigenesis (recreation) Establishment of the germline Extavour and Akam, Development 130:5896 (2003)

  8. Preformation Germ cells determinants (germ plasm) are set aside before or at fertilization and remain segregated throughout the lifespan of the organism. C. elegans Drosophila Establishment of the germline

  9. Germline formation in C. elegans In worms, the point of sperm entry defines the posterior pole of the egg. a) A fertilized egg with evenly distributed P-granules b) At pronuclear migration and fusion, P-granules move to the posterior, where the sperm nucleus was located. c) After first cell division all P-granules in Posterior cell. d) At 4-cell stage all P-granules are in Posterior P1 cell

  10. 6 Founder Cells Small posterior cell goes germline Germline formation in C. elegans +98 die +14 die +1 dies

  11. Germline formation in C. elegans 8-cell DAPI staining of nuclei Antibodies to P-granules 24-cell

  12. C. elegans, Drosophila and many other model organisms. Some amphibians, birds. Segregation of mRNAs and proteins required for germ cell formation and function (germ plasm). bruno (RNP-type binding protein, regulates translation) gld-1 (RNA binding protein) mex-1 (zinc-finger DNA-binding protein) vasa (DEAD-box RNA helicase, interacts with eIF5b) germ cell less (transc. repressor, binds E2F) cycB (B-type cyclin, interacts with CDK1, ubiquitous) tudor (Tudor domain containing, part of germ granules) Preformation

  13. Major distinction, no preexisting germ plasm in oocytes. Primordial germ cells are generated during development. Seen in all mammals (so far), many other species. Shared feature with Preformation: germ cells are "set aside" before other cell types. Epigenesis of germline in mammals

  14. Epigenesis of germline in mouse Developmental Cell 2: 537 (2002) Zhao and Garbers, Male Germ Cell Specification and Differentiation Blue = embryonic white = extraembryonic Embryonic Ectoderm Embryonic Mesoderm Embryonic Endoderm

  15. Epigenesis of germline in mouse BMP-4, -8b BMP receptor BioEssays 27.2, Matsui and Okamura, Mechanisms of germ-cell specification in mouse embryos. 2005

  16. Generated by epiblast. Separate from the 3 somatic cell layers. Migrate to gonadal ridge. (Molyneaux et al. Dev. Biol. 240:488 (2001). Populate ridge to form germ cells of gonad. In vitro, PGCs can differentiate into Embryonal Germ Cells (EGC). (Donovan et al. Cell 44:831 (1986), Matsui et al. Cell 70:841 (1992)). This differentiation is similar to the "reprograming" of somatic nuclei seen in Oocytes and ES cells. EGCs are one of only a few pluripotent stem cells currently known. Can contribute to all cell types in embryos. Primordial germ cells

  17. Human Embryonal Germ Cells Human EGCs Mouse ES cells Shamblott et al. PNAS 95:13726 (1998) Cells were grown in DMEM supplemented with 15% fetal bovine serum, 0.1mM nonessential amino acids), 0.1 mM 2-mercaptoethanol, 2 mM glutamine, 1 mM sodium pyruvate, 100 units/ml of penicillin, 100 ug/ml of streptomycin, 1,000 units/ml of human recombinant leukemia inhibitory factor (hrLIF), 1 ng/ml of human recombinant basic fibroblast growth factor (hrbFGF), and 10 mM forskolin.

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