Stem Cell

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Stem cells are unique cells with

the ability to self-renew and


differentiate into various
specialized cell types. They are
fundamental to development,
tissue maintenance, and repair.
Symmetric Division: Both daughter cells retain the
same characteristics as the parent stem cell,
allowing for expansion of the stem cell pool.

Asymmetric Division: Explanation: One


daughter cell retains stem cell properties,
while the other begins differentiation.

During asymmetric division, a stem cell divides into


two daughter cells with different fates:

Stem Cell: One daughter cell retains the properties


of the original stem cell, maintaining the stem cell
pool.
Progenitor Cell: The other daughter cell becomes a
progenitor cell, which is committed to
differentiating into a specific lineage but may
undergo several more divisions before fully
differentiating.
During asymmetric division, a stem cell divides into two daughter
cells with different fates:

Stem Cell: One daughter cell retains the properties of the original
stem cell, maintaining the stem cell pool.

Progenitor Cell: The other daughter cell becomes a progenitor cell,


which is committed to differentiating into a specific lineage but may
undergo several more divisions before fully differentiating.
• Progenitor cells act as an intermediate stage between a stem
cell and fully differentiated cells. They are responsible for
producing a large number of specialized cells necessary for
tissue development, growth, and repair.
• Unlike stem cells, progenitor cells typically have a limited
capacity to self-renew. They undergo a finite number of
divisions before differentiating completely.

• Progenitor cells are more specialized than stem cells. For


example, a neural progenitor cell can give rise to various Stem cell division and differentiation. A - stem cell; B -
progenitor cell; C - differentiated cell; 1 - symmetric stem
types of neurons or glial cells, but it cannot produce cells cell division; 2 - asymmetric stem cell division; 3 -
outside the nervous system. progenitor division; 4 - terminal differentiation
Lineage: A cell lineage is the developmental history of a cell as it progresses from an undifferentiated state (such as a
stem cell) through various stages of division and differentiation to become a specific cell type with a distinct function.
Lineage Specification: This is the process by which a cell becomes committed to a particular developmental pathway or
cell fate. During this process, cells gradually lose the potential to become other cell types and become more specialized.

Potency refers to the potential of stem cells to


differentiate into different cell types.

• Totipotent: Can form all cell types, including


extraembryonic tissues (e.g., zygote).

• Pluripotent: Can differentiate into almost any


cell type in the body (e.g., embryonic stem
cells).
• Multipotent: Limited to forming cell types within a
particular lineage (e.g., hematopoietic stem cells
forming blood cells).

• Unipotent: Can produce only one cell type but can


self-renew (e.g., muscle stem cells).
stem cell niche
Adult stem cells reside in a physiologically limited specialized anatomical microenvironment, or niche, which
supports stem cells.
COMPONENTS:
•Cellular Components: These include neighboring differentiated cells,
other stem cells, and a variety of other cell types that may secrete
factors affecting stem cell behavior.
•Extracellular Matrix: This is a network of proteins and carbohydrates
that not only provides structural support but also helps in cell signaling.
•Soluble Factors: These are biochemical factors such as growth factors,
hormones, and cytokines that are secreted by cells and have the ability
to influence stem cell behavior.
•Vascular and Neural Inputs: Blood vessels and nerves can also form
part of the niche, providing essential nutrients and other signaling
molecules.
ROLE:
•Self-Renewal: The niche often secretes specific factors that help maintain
stem cells in an undifferentiated state.
•Differentiation: When required, the niche provides signals that encourage
stem cells to differentiate into specialized cell types.
•Migration and Homing: The niche plays a role in guiding stem cells to their
appropriate locations during tissue repair or during regular turnover of cells.
•Protection: In some instances, the niche acts as a sanctuary, protecting stem
cells from pathogens, toxins, or other unfavorable conditions.
Differentiation of cells
iPSCs

Induced pluripotent stem (iPS) cells, are a type of pluripotent stem cell derived from adult somatic cells. They have
been reprogrammed through inducing genes and factors to be pluripotent.

iPSCs were first created in 2006 by Shinya Yamanaka and his


team, a breakthrough that earned him the Nobel Prize in
Physiology or Medicine in 2012

Introduction of four specific genes (named Myc, Oct3/4, Sox2 and


Klf4), collectively known as Yamanaka factors, encoding transcription
factors could convert somatic cells into pluripotent stem cells.

Myc is a family of regulator genes and proto-oncogenes

Oct3/4: It is critically involved in the self-renewal of undifferentiated embryonic stem cells

Sox2 is essential for maintaining self-renewal, or pluripotency, of undifferentiated embryonic stem cells

KLF4 is involved in the regulation of proliferation, differentiation, apoptosis and somatic cell reprogramming
Generation of iPSCs
Somatic Cells: Start with differentiated adult cells, such as skin fibroblasts.
Reprogramming Factors: Introduce a set of specific genes (usually four key transcription factors:
Oct4, Sox2, Klf4, and c-Myc, known as the Yamanaka factors) into these cells.
Gene Introduction Methods:
•Viral Vectors: The most common method, using retroviruses or lentiviruses to insert the
genes into the cell’s DNA.
•Non-Viral Methods: Include plasmid transfection, mRNA, or small molecules to avoid
potential risks associated with viral integration.
Reprogramming Process: Over a few weeks, the introduced genes reprogram the somatic cells to
revert to a pluripotent state

https://www.youtube.com/watch?v=2yolY8anIQo
Applications of iPSCs

Regenerative Medicine: Potential for repairing damaged tissues or organs, such as heart cells for heart disease or
neurons for neurodegenerative diseases.

Disease Modeling: iPSCs can be derived from patients with specific genetic disorders to create models of diseases like
Parkinson’s, ALS, or diabetes. This allows for the study of disease progression and the testing of new drugs.

Drug Screening and Development: iPSCs provide a platform for high-throughput screening of drug candidates in a
personalized manner.

Toxicology Testing: Testing the effects of drugs or chemicals on various cell types derived from iPSCs to assess safety

Disadvantages

Genomic Stability: Concerns about potential mutations during reprogramming or prolonged culture.

Efficiency of Reprogramming: The reprogramming process is not 100% efficient, and not all cells become fully pluripotent.

Safety Issues: The use of viral vectors, particularly with oncogenes like c-Myc, raises the risk of tumorigenesis, although newer,
non-integrating methods are being developed.

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