pluripotent stem cell

**Potency hierarchy (high-yield):** - Totipotent: can form an entire organism, including extraembryonic tissue (zygote and blastomeres up to ~8-cell/morula stage). - Pluripotent: can form all three germ layers (and germ cells) but not extraembryonic tissue. Examples: embryonic stem cells (ESCs) from the inner cell mass (embryoblast) of the blastocyst, and iPSCs. - Multipotent: limited to a particular lineage or tissue (e.g., hematopoietic stem cells give rise to all blood cell lines; mesenchymal stem cells give rise to bone, cartilage, and fat). - Unipotent: a single cell type (e.g., spermatogonial stem cells, epidermal basal stem cells).

**Key features:** - Unlimited self-renewal (asymmetric division produces one stem cell and one differentiating daughter) and high telomerase activity. - Pluripotency markers: Oct4 (POU5F1), Sox2, Nanog. - Embryology: the blastocyst has an outer trophoblast, which forms the placenta (cytotrophoblast and syncytiotrophoblast), and an inner cell mass (embryoblast), which is pluripotent and forms the epiblast and hypoblast. The epiblast gives rise to all three germ layers through gastrulation.

**Induced pluripotent stem cells (iPSCs):** - Yamanaka (Nobel Prize 2012, shared with Gurdon) reprogrammed adult somatic cells (e.g., fibroblasts) to a pluripotent state using four transcription factors: Oct4, Sox2, Klf4, and c-Myc (the "OSKM" factors). - Advantages: patient-specific, so there is less risk of immune rejection, and they avoid the ethical issues of destroying embryos. - Applications: disease modeling, drug screening, and regenerative medicine. - Risks: teratoma formation (a tumor with tissue from all three germ layers, seen when undifferentiated pluripotent cells are transplanted), genomic instability, and oncogenic potential (c-Myc, Klf4).

**Clinical correlations:** - Teratomas and germ cell tumors reflect pluripotent-like cells. Embryonal carcinoma has pluripotent features (Oct4+, CD30+), and mature teratoma (e.g., ovarian dermoid cyst) contains tissue from all three germ layers. - Hematopoietic stem cells are multipotent, not pluripotent. They are CD34+ and are used in bone marrow transplantation. - Therapeutic cloning (somatic cell nuclear transfer) can also generate patient-specific ESCs.

**Board pearl:** If a question asks which cell can give rise to all three germ layers but not the placenta, the answer is a pluripotent cell (inner cell mass/ESC). If it asks about the cell that can form the placenta as well, the answer is totipotent (zygote/early blastomere).