Efficient directed differentiation requires a detailed understanding of the lineage and cell fate decision, often provided by developmental biology.
[2][4] During differentiation, pluripotent cells make a number of developmental decisions to generate first the three germ layers (ectoderm, mesoderm and endoderm) of the embryo and intermediate progenitors,[5] followed by subsequent decisions or check points, giving rise to all the body's mature tissues.
Developmental biology and embryology provides the basic knowledge of the cell types' differentiation through mutation analysis, lineage tracing, embryo micro-manipulation and gene expression studies.
Cell differentiation and tissue organogenesis involve a limited set of developmental signaling pathways.
Directed differentiation consists in mimicking developmental (embryo's development) decisions in vitro using the stem cells as source material.
[9] A drawback of this approach is the introduction of foreign nucleic acid in the cells and the forced expression of transcription factors which effects are not fully understood.
[6] Several application domains emerged: For basic science, notably developmental biology and cell biology, PSC-derived cells allow to study at the molecular and cellular levels fundamental questions in vitro,[5] that would have been otherwise extremely difficult or impossible to study for technical and ethical reasons in vivo such as embryonic development of human.
[8] More complex processes can also be studied in vitro and formation of organoids, including cerebroids, optic cup and kidney have been described.
[2][5] These applications are limited to the cell types that can be differentiated efficiently and safely from human PSCs with the proper organogenesis.
Source material can be normal healthy cells from another donor (heterologous transplantation) or genetically corrected from the same patient (autologous).