Cell proliferation and differentiation

By Prof. Dr Shefaa El Sawy Prof Dr Safinaz Safwat

Cell proliferation

An increase in the number of cells as a result of cell growth and cell division

Cell differentiation:
The processes

Specialized cell having specific structural, functional, and biochemical properties.

involved in commitment of a cell to a specific fate. Or The process whereby relatively unspecialized cells, e.g. embryonic or regenerative cells, acquire specialized structural and/or

Unspecialized cell

Specialized cell (e.g., white blood cell)

Differentiate

Cell proliferation in embryo

Early development is characterized by the rapid proliferation of embryonic cells, which then differentiate to produce the many specialized types of cells that make up the tissues and organs of multicellular animals.

As cells differentiate, their rate of proliferation usually decreases, and many cells in adult animals are arrested in the G0 stage of the cell cycle.

Cell

After differentiatio n

Few cells cannot enter the cycle

Some cells continuously cycling cells to replace cells that have a high rate of

Most cells in adult animals are arrested in the G0 stage & resume proliferation on demand

Constant number of cells in adult tissues and organs.

Cell proliferation = cell death

Cell proliferation in adult

The cells of adult animals can be grouped into three general categories:
1.

Tissues with permanent cells : Static cell population or non-dividing. Renewal by simple duplication of existing simple cells (stable cell population or quiescent cells. Renewal by stem cells (continuously divining or labile cells)

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They leave the cell cycle to perform specialized functions. These cells are no longer capable of cell division. They would not be replaced ifinjured or lost

Static cell population or non-dividing.

TDTerminal differentiated cell such as 1. 1- neuron 2. cardiac muscles 3. Lens cells 4. skeletal muscles.

They do not usually divide, and considered to be in G0 stage. They can be triggered to divide by appropriate signals as injury.

Stable cell population or simple quiescent cellsduplication of existing cells

1.

These cells divide to give pairs of daughter cells of the same type.

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smooth muscle cells. endothelial cells. epithelial cells of most internal organs.

Renewal by stem cells = continuously divining or The fully labile cells Stem cell differentiated cells
do not proliferate but are replaced by the proliferation of less differentiated cells, called stem cells
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Stem cell

Se l f-

Specialized cell (e.g., white blood cell)

Renewal by stem cells = continuously divining or Serving as a source labile cells cell Stem for the production
Se l f-

of differentiated cells throughout life. They include all cells that have short life span.

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Stem cell

Specialized cell (e.g., white blood cell)

1.

blood cells.

1.

Epithelial cells of the skin.

Stem Cells Definition

1.

They are primal cells which are the source, or stem, for all of the specialized cells that form organs and tissues.

Stem cell
al

They Are undifferent iated master cell that do not yet have a found in all multiThey are specific organisms that cellular retain the function ability to produce
through mitosis both a selfrenewing stem cell and a second cell with the capacity to differentiate into more specialized cells.

Can undergo unlimited cell division (selfrenewal)

2.

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Se lfr

te tia

Stem cell

3Specialized cell (e.g., white blood cell)

under proper conditions

functions of stem cells

1.

Play a key role in the development of multicellular organism.

In a developing embryo: differentiate into all of the specialized embryonic tissues.

In adult organisms: act as a

1.

Providing cells for renewal and regeneration of adult tissues.

repair system for the body giving rise of specialized cells. Required to replace differentiated cells that cannot divide themselves if the terminal state of cell incompatible with cell

Striated muscle differentiation is outer most layer of red blood division. cells

What is Stem Cell Niche?

The microenvironment in which stem cells are found, which interacts with stem cells to regulate stem cell fate They are created by tissue cells and the extracellular matrix. Stem cells growth and differentiation depend on the combination of extrinsic and

Factors that regulate stem cell within the niche

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cell-cell interactions between stem cells interactions between stem cells and adhesion molecules

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3.

interactions between stem cells and neighboring stromal niche cells

Niche cells anchor stem cells with adherens junctions to provide cell surface and secrete proteins activating signaling pathways to regulate the cell cycle of the stem cell. Some of these factors stimulate division; others

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extracellular matrix components the oxygen tension growth factors Cytokines

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physiochemical nature of the environment including the pH, ionic strength

Embryonic stem cell niche

Click to edit Master text styles Second level Third level Fourth level Fifth level

During embryonic development, various niche factors act on embryonic stem cells to induce their proliferation or differentiation

Adult stem cell niche

Maintain adult stem cells in a quiescent state, until needed: stem cell storage. In tissue injury, the surrounding microenvironment actively gives signals to stem cells to either promote self renewal or differentiation to form new tissues. Stem cell niches occur in every organ in the body that can regenerate this organ if damaged (organ specific stem cells)

STEM CELL PROPERTIES

1-

Self-renewal: the ability to go through numerous

cycles of cell division while maintaining the undifferentiated state.

2- Potency: the capacity to differentiate into

different cell types (either totipotent or pluripotent).

Multipotent or unipotent progenitor cells are also referred to as stem cells.

According to their potency (Differentiation capability), stem cells can be classified into different cell types:

Types of stem cells

Stages of Embryogenesis
Egg sperm

Morula

2-cell embryo Fertilized egg

Multi-cell embryo
Outer cells (forms placenta) Inner cells (forms fetus)

Day 11-14 Tissue Differentiation

Day 5-6 Blastocyst

Totipotent stem cells:

Totipotent means entire. They have the potential to generate all the cells and tissues that make up an embryo. Can construct a complete, viable, organism. Produced from the fusion of an egg and sperm cell (first few divisions; morula's cells).

Pluripotent stem cells

Pluri means several or many. They are derived from the inner cell mass of the blastocyst They can differentiate into all derivatives of the three primary germ layers: ectoderm, endoderm, and mesoderm. They can form most types of tissue found in the human body, they cannot form an organism

Multipotent stem cells:

can produce only cells of a closely related family of cells.
1.

hematopoietic stem cells differentiate into red blood cells, white blood cells, and platelets.

2.

epithelial stem cells that give rise to the various types of skin cells.

Most adult stem cells belong to this category

Unipotent cells:
Means one. Can produce only one cell type, but have the property of self-renewal which distinguishes them from nonstem cells. eg.: -Muscle satellite cells that contribute to differentiated muscle tissue.

SOURCES OF STEM CELLS FOR (Where do stem cells come from?)

Four potential sources for stem cells

1.

Embryonic stem cells (ES cells). Adult stem cells. Amniotic fluid stem cells. Induced pluripotent stem cell.

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Sources of Stem Type Source potency Differentiat Cells ed cell type

1- Embryonic4- 5days old embryo (blastocyst) stem cells
pluripotent stem cells Any of the 220 cell types present in the human body (e.g., skin cells, liver cells, etc.)

Advantage of use of ESC:

1.

They can divide into more stem cells or they can specialize and become any type of body cell so they are used to regenerate or repair many diseased tissue and organs. Represent an ideal source for tissue regeneration as they are immunologically inactive.

2.

The limited use of ES cells in stem cell therapy is due to:

Ethical restriction as they come from destroyed human embryos. Being pluripotent (requiring specific signals for correct differentiation) carry a high incidence for the development of tumors.

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2.

Types of Stem Type Source potency Differentiat Cells ed cell type

2- Adult stem cells
Refer to any cell Most are multipotent A found in a developed stem cells Organ organism that has specific stem the properties of cell stem cells ( in children and adult) Develop into the same cell types. E.g., blood stem cells can develop into several blood cell types, but cannot develop into brain, kidney, or liver cells.

B Taken from Umbilical cord umbilical cord stem blood C Fetal stem cells

pluripotent stem cells

Taken from organs ofPluripotent or fetuses at a later multipotent stage of stem cells development

Types of Stem Type Cells Source potency Differentiat ed cell type

3- Amniotic Resided in floats fluid stem freely in the cells amniotic fluid of pregnant women 4- Induced Dedifferentiated pluripotent adult somatic stem cell cells through alteration of genes multipotent stem cells Develop into closely related family of cells. pluripotent stem cells

Amniotic fluid stem cells:

Advantage of usage:
1. The cells, shed by the developing fetus and easily retrieved during routine prenatal testing,. 2. Easier to maintain in laboratory dishes than embryonic stem cells. 3. The cells are a genetic match to the developing fetus will not be rejected if used to treat birth defects in that newborn. 4. The cells could be frozen, providing a personalized tissue bank for use later in life.

Induced pluripotent stem Advantage: cell

new technique may help researchers to avoid the limitations of embryonic stem cells. Disadvantage: The technique involves processes that may not be safe for use in people.

The uses of stem cells and their clinical applications: cell culture of
Stem cell forms the core of a new field "regenerative medicine".
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adult stem cells

In transplant therapy: e.g. to replace or restore tissue that has been damaged by disease or injury.

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Regenerating bone using cells derived from bone marrow stroma. Treatment of type1 diabetes by developing insulin-producing cells. Repairing damaged heart muscle following a heart ischemia. Treatment of Alzhiemers disease. Treatment of leukemia

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Used to study and screen new therapeutic drugs Develop model systems to study normal growth and identify the causes of birth defects. Advance knowledge about how an organism develops from a single cell and how healthy cells replace damaged cells in adult organisms.

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