Cell Fate Determination: How Cells Choose Their Paths in Developing Tissues

By Marzia KhanReviewed by Danielle Ellis, B.Sc.

Cell fate determination is a key component of development biology and tissue development. It is controlled by complex intracellular molecular regulatory networks, referring to the future of the cell, including which cell ‘type’ it is progressing towards.

A variety of factors, including endogenous developmental factors, interaction between neighboring cells, and external long-distance signals, such as morphogens and hormones, can determine the fate of cells.

Mechanical cues are used to regulate cell fate and shape tissue development as well as homeostasis, which can be seen when there is a higher level of dysregulation of tissue forces that can increase the risk of tissue malignancy, leading to tumor aggression and treatment resistance.

Ultimately, cell fate determination is caused by acquiring new characteristics that occur through variations in transcription.

The Genetic Orchestra of Cell Differentiation

Genetic regulation is a dynamic process involving the regulation of gene expression and changes in transcription during cell differentiation that can impact the phenotype of various cell types.

As all cells within a complex multicellular organism carry the same DNA, the combination of genes that are expressed or ‘turned on’ or are repressed or ‘turned off’ can result in cell fate determination into different cell types.  

Interestingly, a mature mammalian somatic cell can be reprogrammed and acquire a drastically different gene expression profile as a result of being exposed to reprogramming stimuli. This type of induction involves genetic ‘switches’ of thousands of functionally heterogeneous genes that can be turned ‘on’ and ‘off’ in order to impact cell signaling pathways, leading to altered morphological features and varied physiological behaviors.

These differences in gene expression can be regulated by cues from within a cell as well as externally and the interactions between these cell signaling indicators and the genome impact all cellular processes that occur during embryonic development and in adults.

Gene expression regulation is mediated by many different molecules, including transcription factors, that are key regulators of cellular processes, including both intrinsic and extrinsic signals. Transcription factors are common drivers of cell differentiation and reprogramming processes, which can cause chromatin to open for other factors to bind or even block the binding of other factors, and this can activate or repress gene transcription.

An example includes the Yamanaka factors that can be used for stem cell differentiation, with these factors being used to reprogram fibroblasts into induced pluripotent stem cells, such as for specific differentiation into other cell types.

Cellular Communication: Signals That Shape Destiny

Cell signaling pathways are critical for organisms to coordinate cellular activities as well as metabolic processes, with cells receiving and processing signals that occur both intrinsically and extrinsically. These signals are predominantly chemical, with multicellular organisms using growth factors, hormones, neurotransmitters, and extracellular matrix molecules in order to ‘communicate.’

More specifically, neurotransmitters consist of short-range cell signaling molecules that can travel across small spaces, such as between neurons and muscle cells. However, other types of signaling molecules work differently. They are required to span a larger distance in order to reach their targets, such as the follicle-stimulating hormone that travels from the brain to the ovary in order to stimulate the release of eggs.

Additionally, Notch, Hedgehog, and Wnt are part of significant cell signaling pathways in developmental biology and play a critical role in the transformation of a single-cell zygote into a complex multicellular organism. These cell signaling pathways are involved in the regulation of core cell processes such as cell proliferation, differentiation, and migration, which are critical for tissue development and overall developmental biology.

Dysregulation of these critical cell signaling pathways can result in disease development, leading to cancer formation as well as causing resistance to anticancer therapies.

The Influence of the Microenvironment

Cell interactions that involve mechanical cues aid in regulating cell fate as well as directing tissue-specific development. Cells within tissues can sense viscoelastic properties from the extracellular matrix (ECM) as well as material properties from neighboring cells via specialized protein receptors. In turn, cells can respond through localized or diffuse mechanically responsive sensors that can translate the cues into biochemical signals through adaptor proteins and second messengers.

Additionally, cells can also alter the structure of the mechanosensors on their cell surface in response to extracellular stresses or changes to the extracellular matrix. An example includes integrins that go through conformational changes in order to shift from a folded-to-stretched state in response to ECM stiffness to enable ligand binding.

Fibroblasts hold a significant role in the ECM, with these cells being the most commonly found and being involved in the production and secretion of components of the ECM that support critical organ function. These cells provide key cellular niches and positional information for neighboring cells through microarchitectural, biochemical, and biomechanical indicators in the ECM, as well as being responsible for secreting mediators, including cytokines and growth factors.

Stem Cells and Their Potential in Tissue Engineering

Stem cells are significant in developmental biology and tissue development, with these special cells having a unique capacity for self-renewal as well as to differentiate into multiple cell lineages.

These cells are considered building blocks of tissues and organs and can be used for repair and critical advances in fields such as tissue engineering and regenerative medicine. Understanding cell fate determination is critical for these advancements, with stem cells differentiating and proliferating into various cell types for continuing development at the neonate stage of life.

Experimental Techniques in Studying Cell Fate

Lineage tracing is a ubiquitous technique for studying cell fate determination, with the ability to track migration, proliferation, and differentiation of specific cells in vivo. This is significant because cells have different roles in movement, migration, and differentiation for specific organs or physiological needs. Tracing the fate of particular cells can allow for further understanding of organogenesis as well as physiological and pathological processes.

In vitro lineage tracing technology approaches include labeling methods such as DNA transfection, viral transduction, and in situ hybridization, while in vivo methods consist of gene targeting technology, barcode technology, and single-cell RNA sequencing. These strategies have various advantages and disadvantages, including monitoring organ formation, tissue damage, and regeneration.

Advanced genetic tracing tools hold great potential in cell fate determination, with a significant role in tissue development, detection of genetic knockouts, and its applications for innovative disease research.

Further Reading

• All Cell Biology Content
• What is Cell Biology?
• What is Bioethics?
• Taxonomy, Nomenclature, and Classification: Key Terms in Biology and the Life Sciences
• Cell Biology and Toxicology