Screening for regulators of human embryonic axis elongation in vitro

点击翻译按钮获取中文摘要

Directing pluripotent stem cells (PSCs) to generate ("differentiate") various cell types in the petri dish is an attractive tool for understanding how embryos develop and a promising route towards therapies. However, our ability to produce cell types corresponding to the lower spinal cord (the thoracic, lumbar and sacral regions) and skeletal muscle is currently very limited. This is because conventional PSC differentiation methods fail to produce the common embryonic precursor of these cell types known as neuromesodermal progenitors (NMPs). We have recently succeeded in devising a protocol for converting efficiently human PSCs into NMPs (hNMPs). These in vitro generated NMPs appear to be a promising starting material for producing lower spinal cord and skeletal muscle cells. However, we still do not know much about the signals and the molecular mechanisms driving the generation of these cell types from hNMPs. The experiments proposed here will test various chemicals in order to identify the best "recipes" for pushing human NMPs to become exclusively either lower spinal cord or skeletal muscle cells. We will also examine how the binding of certain proteins known as transcription factors to the DNA of NMPs influences their decision to remain NMPs or differentiate into spinal cord/skeletal muscle cells. This work will lead to a better understanding of NMP biology and pave the way for the use of their differentiation products in the clinic.