Stem Cell Lecture Flashcards

Introduction to Stem Cells and Tissue Regeneration

• Stem cells are critical for the maintenance and regeneration of tissues in the body.

• This section covers stem cells in vivo (in the body) and in vitro (in controlled environments).

Overview of the Week's Topics

• Stem Cells and Their Renewal: Understanding how stem cells reproduce and maintain themselves.

• Stem Cells in Vivo: Examining hierarchical stem-cell systems, particularly in blood cell formation.

• Stem Cells in Vitro: Discussing pluripotent stem cells and techniques for cell reprogramming.

Defining Stem Cells

• Self-Renewal: Ability to divide and produce identical stem cells over long periods.

• Unspecialized Nature: Stem cells have not yet differentiated into specialized cells.

• Differentiation: Process by which stem cells become specialized cells (Becker et al., 1963; Till and McCulloch, 1961).

Types of Stem Cells

• Totipotent Stem Cells:

  • Can develop into the entire embryo and placental tissues (e.g., zygote cells).

• Pluripotent Stem Cells:

  • Can form all cell types in an organism (e.g., embryonic stem cells (ESC), induced pluripotent stem cells (iPSC)).

  • Key Experimental Techniques: Tetraploid embryo complementation and embryo chimerism.

• Multipotent Stem Cells:

  • Can differentiate into multiple specialized cells (e.g., hematopoietic stem cells (HSC)).

• Unipotent Stem Cells:

  • Can generate only one type of specialized cell (e.g., muscle stem cells).

• Progenitor Cells:

  • Intermediate cells with limited potential for self-renewal, giving rise to a limited number of specialized cells.

Stem Cell Division and Differentiation

• Division of stem cells can lead to either more stem cells or differentiated cells.

• Symmetric vs. Asymmetric Division:

  • Symmetric: Both daughter cells remain stem cells or differentiate.

  • Asymmetric: One cell remains a stem cell while the other differentiates.

• Niche: The microenvironment affecting stem cell fate determination (Schofield, 1978).

Adult Stem Cells in Vivo

• Located in various tissues, including:

  • Intestinal Crypts

  • Muscle Tissue

  • Bone Marrow: Where blood-forming stem cells reside.

Haematopoietic Stem Cells (HSCs)

• HSCs give rise to all blood cell types:

  • Red Blood Cells: All look alike and are responsible for oxygen transport.

  • White Blood Cells: Divided into three main classes (neutrophils, lymphocytes, and eosinophils).

• Production Control: Each cell type's production in the bone marrow is intricately controlled.

Mechanisms Influencing Blood Cell Formation

• Commitment Process: A stepwise commitment ensures a rising number of specialized cells.

• Interactions With Stromal Cells: Signals from the niche and other cells influence blood formation.

  • Erythropoiesis requires the hormone erythropoietin; colony-stimulating factors (CSFs) influence neutrophil and macrophage production.

The Role of Chance in Blood Cell Formation

• Probability Factors Affecting Cell Behavior:

  • Frequency of stem cell division.

  • Probability of cell differentiation and death.

• Resulting outcomes are partly stochastic, indicating variability in stem cell fate.

Key Learnings from Stem Cells in Vivo

• Distinctions among totipotency, pluripotency, and multipotency.

• Concepts of self-renewal and differentiation in blood cell formation.

• Regulation mechanisms in blood formation.

Transition to Stem Cells in Vitro

• Introduction to iPSCs and techniques for cell reprogramming.

• Experimental derivation of pluripotent stem cells from various sources.

Reprogramming Techniques

• Reprogramming: Transforming somatic cells into pluripotent stem cells and techniques for deriving embryonic stem cells (ESCs).

• Methods include:

  • Teratoma formation.

  • Directed differentiation into specialized cell types.

  • Work with adult stem cells in culture (e.g., Neuroprogenitor cells).

Applications of Stem Cells

• Use in drug discovery and analysis of diseases.

• Development of cellular therapies for transplantation and disease modeling.

• Importance of understanding the pluri- and multipotent nature of stem cells for clinical applications.

Research Questions and Challenges

• Determining factors influencing size in cells, tissues, and organs.

• Fundamental molecular differences defining stem cells.

• Maintaining the balance between stem cells, progenitor cells, and differentiated cells.

• Role of chromatin structure in cell memory.

Resources

• Reference: Alberts et al. (Sixth Edition, Molecular Biology of the Cell, Chapter 22).

• ISSCR Core Concepts in Stem Cell Biology: ISSCR Document.