Lecture 34: Tissue Maintenance and Stem Cells

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What three cellular processes maintain tissue organization?

Cell communication, selective cell adhesion, and cell memory

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What kind of signaling is required for cell survival?

Continuous signals from neighboring cells

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What type of interactions allow sorting out of cells in tissues?

Homophilic cadherin interactions

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What are three examples of cell memory?

Stable patterns of gene expression, chromatin structure and DNA methylation

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What role does selective cell-cell adhesion play in forming tissues?

It facilitates the sorting out of cell populations through homophilic interactions between cell adhesion molecules.

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What stage are most cells arrested in, in adult animals?

G0 stage

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How are cells renewed in tissues?

Via the proliferation and differentiation of stem cells

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Where are stem cells located in the epidermis (skin)?

In the basal layer

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How often are intestinal cells typically replaced?

Every few days

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What are the two main properties of stem cells?

They can renew themselves for long periods through cell division, and they are unspecialized but can give rise to more than one differentiated cell type.

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What are the three types of stem cells?

Adult (somatic) stem cells, embryonic stem cells (ES cells), and induced pluripotent stem cells (iPS cells).

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Are adult stem cells usually scarce or abundant in mature organs?

Scarce

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Are somatic stem cells multipotent or pluripotent?

Multipotent

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What are somatic stem cells specialized for?

Maintaining a particular type of tissue

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What is the precursor of all blood cells?

A hematopoietic stem cell (HSC)

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How was the existence of stem cells demonstrated in bone marrow?

Bone marrow transplantation experiments

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What determines “stemness” on a molecular level?

A combination of transcription factors, transmembrane receptors, cell cycle regulators and other proteins that cooperate to keep a cell in an undifferentiated state.

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Where do “stemness” signals come from?

A stem cell niche

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Define a stem cell niche.

A microenvironment that promotes stem cell maintenance

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What does the niche control?

The crucial choice between self-renewal and differentiation

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What type of signaling maintains cell proliferation in the intestine?

Wnt signaling

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Name some diseases that cell-based therapies may provide a cure for.

Parkinson’s and Alzheimer’s diseases, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis, rheumatoid arthritis.

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What is bone marrow transplantation used for?

To replace hematopoietic cells for blood cancer patients

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What is a challenge of effective stem cell therapy in regards to cell quantity?

Must be able to generate sufficient quantities of cells to create a tissue (need unlimited replication potential).

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Why are cells from the same patient preferred in stem cell therapy?

Transplanted cells must be able to survive in the recipient (graft must not be rejected) and integrate into the surrounding tissue.

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What kind of reprogramming resulted in the generation of embryonic stem cells (ES cells)?

Somatic cell nuclear transfer (SCNT)

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What does reprogramming require?

Large-scale changes in chromatin structure and gene activity

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What is an ES cell?

Embryonic Stem Cell

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What process can ES cells be generated by?

Somatic cell nuclear transfer

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What are the properties of embryonic stem cells (ES cells) that make them ideal for cell-based therapies?

Pluripotency and high proliferation potential

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What is a multi-step treatment of cultured ES cells with growth factors and other bioactive molecules used for?

Directed differentiation into specialized cells

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What are the induced pluripotent stem cells also known as?

iPS cells

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What have induced pluripotent stem cells (iPS cells) revolutionized?

Cell-based therapies

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What is the advantage of using iPS cells for cell-based therapies?

Full self-compatibility if donor and recipient are the same person, and use is free from ethical concerns associated with generation of ES cells

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What factors reprogram somatic cells into iPS cells?

Three transcription factors

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What discovery was J. Gurdon and S. Yamanaka awarded the Nobel Prize in Physiology or Medicine in 2012 for?

The discovery that mature cells can be reprogrammed to become pluripotent

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What are organoids?

Miniature organs

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What do organoids allow for?

A highly controlled study of organ development and disease

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What is directed differentiation?

A process used in the process of differentiating cells into specialized cells.

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How can you prove that iPS cells are pluripotent?

By testing if iPS cells can support complete mouse development