Tissue and stem cell 2

Embryonic Stem Cells (ESCs): Obtained from the inner cell mass (ICM) of the blastocyst, these are pluripotent.
Adult/Tissue Stem Cells: Typically multipotent or unipotent, found in specific tissues such as the bone marrow (hematopoietic stem cells) and the intestinal crypt.
Induced Pluripotent Stem Cells (iPSCs): Created by forced reprogramming of adult somatic cells to acquire pluripotent stem cell characteristics through the expression of specific transcription factors (Oct4, Sox2, Klf4, Myc).

Experiment: mouse stem cell in intestinal crypt labelled with β-Gal (blue) proliferate and occupy the entire crypt, with its progeny forming ribbon that streams up to the tip of the vili.
Mitotic stem cells at the base of the crypt are exposed to Paneth cells that signal for rapid asymmetric cell division.
Transit amplifying cells differentiate on their way to the tip of vili and undergo apoptosis once reached the tip. Dead cells are shed into the intestinal lumen.
Lateral inhibition: Notch signaling maintains stem cell proliferation. Notch signalling also promotes the development of Absorptive Progenitor (AP) while represses Secretory Progenitor (SP). High Notch ligand Delta levels promotes AP development by repressing Math1, a transcription factor that promotes SP development. In contrast, low Delta allows expression of Math which leads to SP development.
Experiment with chimeric/confetti mice illustrated competition among stem cells in the niche, leading to a dominance of certain stem cell lineages (that divides symmetrically to produce two stem cells or divides asymmetrically) over time. This is seen in the observation that a polyclonal stem cell pool is replaced by one that is monoclonal.

Multipotent and self-renews but also gives rise to lymphoid (lymphocytes and killer cells) and myeloid lineages (erythrocytes, platelets and macrophages etc).
Bone marrow transplants are mostly autologous, using the patient’s own bone marrow. The procedure is risky and often used to treat acute leukemia and neoplastic lymphoproliferative disorders.

These stem cells in the bone marrow can self-renew and differentiate into lymphoid and myeloid lineages (e.g., lymphocytes, erythrocytes).

Isolated from mouse blastocysts in 1981 by Evans, Kaufman, and Martin.
Derived from ICM, they aggregate to embryoid bodies that differentiate into various cell types given certain culture conditions.

Sickle Cell Anemia: iPSCs can be corrected for mutations by gene targeting and differentiated into haematopoetic progenitors and then transplanted to rescue sickle cell diseases.
Retinal Organoids: iPSC are differentiated to retinal organoid with expression of Rx gene (Rentinal Homeobox gene). Healthy photoreceptor cells can be isolated from retinal organoids and transplanted to the retina to restore vision in macular degeneration.
- Potential as a treatment for Stargardt’s disease, as demonstrated through successful animal models and ongoing clinical trials.

Culture adaption: Prolonged culture of stem cells leads to selection for cells carrying mutations for enhanced growth. This may lead to overproliferation thus carcinoma/tumor cells that cannot differentiate.
Long-term culture of stem cells can lead to chromosomal abnormalities. Commonly affected chromosomes include Chromosome 1, 12, 17, and 20. Presumably they contain a gene that confers growth advantage in this environment.
Ethical implications of creating human organoids and manipulating stem cells for research and treatments?