Cellular Memory Mechanisms and Differentiation

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Questions and Answers

What is the distinguishing characteristic of cell differentiation?

Reversibility of the cell state

Memory of the differentiated state (correct)

Continuous external signals required

Immediate resetting capability

How does positive feedback affect cellular differentiation?

It decreases the amount of factor A in the cell.

It ceases once the external signal is removed.

It amplifies the initial signal in the cell. (correct)

It disrupts the transcriptional processes.

What role does MITF play in melanocyte differentiation?

It activates the transcription of melanocyte-specific genes. (correct)

It functions only in the presence of MSH.

It inhibits MC1R gene expression.

It reduces cyclic AMP production.

Which master gene regulator is specifically associated with skeletal muscle differentiation?

MYOD1 Signup and view all the answers

What condition can arise from severe mutations in the MITF gene?

Complete lack of pigment cells Signup and view all the answers

What happens once MC1R is present in melanocytes?

Melanocyte differentiation is sustained. Signup and view all the answers

Which factor is NOT part of the four myogenic factors in skeletal muscle differentiation?

CREB Signup and view all the answers

How does MSH influence MITF in melanocytes?

It induces the production of cAMP Signup and view all the answers

What role does ID1 play in non-normal skeletal muscle conditions?

Binds E proteins and inhibits transcription Signup and view all the answers

What are myoblasts primarily known for in the context of muscle development?

Migrating to muscle locations for differentiation Signup and view all the answers

How does telomerase contribute to the immortality of germline cells?

By maintaining telomere length through its RNA complex Signup and view all the answers

Which of the following is a significant feature of senescent cells?

Large, flat morphology with prominent nucleoli Signup and view all the answers

What effect do environmental changes have on ID1 in muscle cells?

They cause ID1 to destabilize and lose its ability to bind Signup and view all the answers

Which marker is commonly associated with cell senescence?

High levels of p16 Signup and view all the answers

What is an effect of cumulative cell divisions on telomeres?

Telomeres shorten as cells divide Signup and view all the answers

Which type of stem cells can differentiate into all functional cell types, including placental cells?

Totipotent stem cells Signup and view all the answers

What is a common implication of cell senescence in aging?

Increased susceptibility to hair greying and skin issues Signup and view all the answers

What type of cells typically express TERT abundantly?

Germline cells Signup and view all the answers

Which pathways are known to be established effectors of cell senescence?

p53, p16, and p21 pathways Signup and view all the answers

What defines a unipotent stem cell?

Ability to form only one functional cell type Signup and view all the answers

Which characteristic is commonly seen in advanced cancer cells regarding cell senescence?

Bypass of regular cell senescence mechanisms Signup and view all the answers

Study Notes

Mechanisms of Cellular Memory

Cellular differentiation is irreversible; once a cell differentiates, it retains that state even without external signals.
Chromatin remodeling plays a role; DNA methylation and histone modifications are copied to daughter cells.

Positive Feedback Mechanisms in Differentiation

Positive feedback describes a self-amplifying loop: an external signal triggers a process that strengthens itself.
Involves master gene regulators (transcription factors controlling specific genes) regulating the production of more of themselves (e.g. MITF for melanocytes, MYOD1 for skeletal muscle). This cycle maintains the differentiation state even when the initial signal stops.

Melanocyte Differentiation

Melanocytes are pigment-producing cells in the skin's epidermis.
Melanocyte stimulating hormone (MSH) and its receptor (MC1R) initiate a signaling cascade.
Cyclic AMP production and activation of MITF (transcription factor), then CREB, lead to the transcription of genes related to melanin production.

MITF and Melanocyte-Specific Genes

MITF production leads to increased production of MC1R and ongoing melanin production, even without continuous MSH stimulation.
A basal level of MC1R activity exists, ensuring melanocyte function even in the absence of MSH.

Microphthalmia-Associated Transcription Factor (MITF)

MITF mutations in mice can lead to the absence of melanocytes, causing small eyes (microphthalmia).
Mutations in MITF are associated with human conditions like Waardenburg syndrome type 2, which involves pigment loss in skin and possibly eyes and can also cause hearing related problems.

Key Transcriptional Regulators of Skeletal Muscle

The myogenic factors (MYOD1, MYF5, MYOG, MRF4) are master regulators controlling skeletal muscle differentiation.
They often work with E proteins in dimers to initiate transcription.
ID1, an inhibitor of differentiation, can block this process.

MYOD Family, E Proteins, and ID1

In normal muscle development, myogenic factors and E proteins work together to promote transcription.
ID1 can bind to E proteins and prevent their interaction with the myogenic factors.
Environmental factors (e.g., reduced growth factors like FGF and IGF) cause ID1 destabilization, leading to muscle differentiation.

Skeletal Muscle Differentiation in Embryos (Simplified)

Myoblasts migrate to muscle formation sites.
Myoblasts express MYOD1, MYF5, ID1, and E proteins.
Reduced FGF and IGF signals cause ID1 destabilization.
Positive feedback from the myogenic factors initiates muscle gene expression through E protein activation and transcription.

Cell Senescence

Cell senescence is the permanent halt in cell division after extended proliferation.
Senescent cells play a protective role against cancer.
Key characteristics of senescent cells include morphological changes (e.g., larger cells, prominent nucleoli), increased lysosomal beta-galactosidase, and the presence of cell cycle inhibitor protein p16.

Telomeres

Telomeres are repetitive DNA sequences (TTAGGG) at chromosome ends.
They protect chromosomes from deterioration and fusion.
Telomeres shorten with each cell division.

Telomerase

Telomerase is an enzyme that maintains telomere length by adding telomeric repeats.
It's active in germ cells to maintain telomere length.
Most somatic cells do not express telomerase, causing telomere shortening.

Telomeres, Senescence, and Cancer

Cancer cells often reactivate telomerase, which leads to immortality.
Senescence acts as a barrier against uncontrolled cell division.
Cancer cells often circumvent or evade senescence mechanisms.

Established Cellular Senescence Pathways

P53, p16, and p21 are senescence pathways that can inhibit cyclin-dependent kinases and halt cell growth.
Deficiencies in senescence pathways can contribute to cancer development.

Senescence and Ageing

Telomere shortening is associated with aging.
Senescence-associated proteins (like p16) increase with age.
Defective telomerase subunits can cause premature aging and disease.
Genetic links exist between p16 locations and various aging-related medical issues such as cardiovascular conditions, type 2 diabetes, frailty and cancer.

Stem Cells

Stem cells are cells with self-renewal and differentiation potential.
Different types of stem cells exist (totipotent, pluripotent, unipotent)
Somatic stem cells exist post-nataly. They also self-renew.
Stem cell senescence contributes to age-related decline in tissues like bone marrow and skin. Stem cells also contribute to ageing.

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Description

This quiz explores the mechanisms of cellular memory and the processes involved in cellular differentiation. It covers topics such as chromatin remodeling, positive feedback mechanisms, and the specific differentiation of melanocytes. Understand the role of transcription factors and signaling pathways in maintaining differentiated states.