APHY 101 3.6
Cell Division, Growth, and Differentiation
Preexisting cell origin: All human cells originate from preexisting cells through the processes of mitosis and cytokinesis.
Embryonic development: Mitotic cell division explains how a single fertilized egg grows and develops into an adult organism consisting of trillions of individual cells.
Cellular specialization diversity: An adult human contains more than 290 specialized cell types, which include 14 unique cell types found exclusively in the embryo or fetus.
Differentiation definition: Differentiation (pronounced DIF-er-en-shee-AY-shun) is the process that guides cell specialization by selectively activating and suppressing the functions of specific genes.
Functional necessity: The capability to continuously generate new cells is essential for tissue growth, ongoing renewal, and injury repair.
Characteristics of Stem Cells and Progenitor Cells
Stem cell definition: Stem cells are unspecialized cells that retain the capacity to divide repeatedly via mitosis without undergoing specialization.
Self-renewal capacity: Self-renewal is defined as the specific ability of a stem cell to undergo division and yield at least one daughter cell that remains an unspecialized stem cell.
Mitotic division outcomes of stem cells:
Division can produce two identical daughter stem cells that continue dividing without specializing.
Division can produce one stem cell daughter and one partially specialized daughter cell.
Progenitor cell definition: A progenitor (pronounced proh-JEN-ih-tor) cell is a partially specialized cell derived from a stem cell that exists as an intermediate state between a stem cell and a fully differentiated cell.
Restricted lineage commitment: Progenitor cells are classified as "committed" because their daughter cells are restricted to developing into a specific, limited set of cell types.
Cellular Lineages and Developmental Fates
Lineage definition: A cellular lineage is the developmental sequence of stem cells and progenitor cells that traces the exact origin of fully differentiated cells.
Neural tissue lineage example: Neural stem cells divide to generate neural progenitor cells, which subsequently differentiate exclusively into specialized neurons and neuroglia; neural progenitors cannot form muscle or bone tissues.
Blood cell lineage example: Hematopoietic stem cells give rise to specialized myeloid progenitor cells, which further differentiate into specialized white blood cells.
Classification by developmental potential:
Totipotent (pronounced toh-TIH-poh-tent): Refers to cells whose daughter cells can differentiate into any specialized cell type in the body. Examples include the fertilized egg and cells from the very early embryo when structured as a small ball of cells.
Pluripotent (pronounced ploor-ih-POH-tent): Refers to cells whose daughter cells can follow any of several developmental pathways, but cannot form every possible cell type. This includes stem cells present later in embryonic and fetal development, as well as adult progenitor cells.
Adult stem cell reservoirs:
Specific stem cells in adults are set aside during embryonic or fetal development to serve as localized repositories for future repair and healing.
Small populations of stem or progenitor cells reside in many adult organs and are triggered to divide upon tissue injury or illness.
Quantitative frequency: In human bone marrow, approximately 1 in 10,000 to 15,000 cells is a hematopoietic stem cell.
Migration and repair: Stem and progenitor cells can travel from the bone marrow through the circulation to replace damaged or dead cells in response to chemical signals released by injured or diseased tissues.
Genetic Equivalence and Selective Gene Expression
Genomic equivalence: Every cell in the human body contains the exact same full set of genetic instructions, with the sole exception of mature red blood cells, which expel their nuclei during maturation.
Differential gene utilization: As cells undergo specialization, they selectively express specific required genes while ignoring or silencing unneeded genes, functioning like a targeted search within a genetic database.
Immature cell terminology: The suffix "-blast" denotes an immature, differentiating cell state (e.g., osteoblast, myoblast).
Osteoblast lineage and function: An osteoblast is an immature bone cell formed from a bone progenitor cell that actively synthesizes proteins needed to bind bone mineral and produces alkaline phosphatase, an enzyme essential for bone tissue formation. It does not synthesize contractile proteins.
Myoblast lineage and function: A myoblast is an immature muscle cell formed from a muscle progenitor cell that selectively accumulates contractile proteins that define muscle function. It does not produce bone mineral-binding proteins or alkaline phosphatase.
Regenerative Medicine and Stem Cell Applications
Regenerative medicine definition: An interdisciplinary field that harnesses the human body's intrinsic capacity to generate new cells to repair damaged tissues and treat medical conditions.
Sources of therapeutic stem cells:
Donor stem cells: Collected from donor bone marrow or umbilical cord blood saved from newborn infants, used to treat metabolic conditions and inherited blood disorders.
Autologous unaltered stem cells: Harvested directly from the patient's own tissue natural sites. In an autologous bone marrow transplant, a patient's stem cells are harvested and set aside, the immune system is ablated using high-dose radiation or drugs, and the unaltered stem cells are re-infused to repopulate the bone marrow.
Reprogrammed patient cells: Differentiated adult somatic cells that undergo cellular reprogramming to return to an unspecialized stem cell state.
Process of producing Induced Pluripotent Stem (iPS) cells:
Differentiated somatic cells (such as skin fibroblasts) are isolated from a patient sample.
Cells are given genetic instructions to express specific proteins that revert them to an unspecialized embryonic stem cell-like state.
Reprogrammed cells are cultured and treated with targeted biochemical cocktails that stimulate division and direct differentiation into specific required cell types (e.g., blood, muscle, or nerve cells).
The resulting specialized cells pass on their modified characteristics to daughter cells and are designed for therapeutic implantation back into the patient.
Case Study: Disease Modeling of Rett Syndrome
Research value of iPS cells: Reprogrammed cells allow scientists to continuously culture specialized cell types—such as mature neurons—that do not naturally divide in the body, enabling direct study of cellular pathology.
Overview of Rett syndrome:
An inherited neurodevelopmental disorder predominantly affecting females.
Clinical characteristics: Uncontrollable and characteristic repetitive hand movements, progressive loss of muscle tone, loss of speech capabilities, decelerated head growth, and severe functional disability by adolescence.
Experimental findings using patient-derived neurons:
Skin samples were taken from four young girls diagnosed with Rett syndrome.
Fibroblasts from the samples were reprogrammed into iPS cells and directed to differentiate into cultured neurons.
Morphological and functional defects identified in Rett syndrome neurons: The cultured neurons were abnormally small, exhibited significantly fewer synaptic connections, and displayed abnormal electrical signaling.
Drug screening results: Pharmaceutical compounds that previously showed efficacy in mouse models of Rett syndrome successfully corrected the observed structural and signaling defects in the cultured human neurons derived from the four female patients, opening pathways for human therapeutic development.
Practice Questions and Review Solutions
Distinguish between a stem cell and a progenitor cell.
Solution: A stem cell retains the capacity to divide repeatedly without specializing, undergoing self-renewal to produce either two daughter stem cells or one stem cell and one partially specialized progenitor cell. A progenitor cell is a partially differentiated, committed intermediate cell whose daughter cells can only specialize into a restricted subset of cell types.
Distinguish between totipotent and pluripotent cells.
Solution: A totipotent cell can give rise to any specialized cell type in the entire organism (e.g., fertilized egg, early cleavage blastomeres). A pluripotent cell can give rise to daughter cells that specialize into many distinct cell types, but cannot form every possible cell type.
Explain how cells differentiate.
Solution: Cells undergo differentiation by selectively activating specific genes required for their specialized function while suppressing the function of unneeded genes within their identical genome.