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Abstract
The adult kidney is derived from the intermediate mesoderm, an early mesoderm subtype located between the paraxial and lateral plate mesoderm. Genetic regulation and fate determination of intermediate mesoderm are poorly understood. The homeobox transcription factor LHX1 is expressed in the developing intermediate mesoderm and is required for the specification of several kidney lineages, but its function in determining IM cell fate is unknown. Throughout this research, I show that LHX1 is necessary and sufficient for differentiation of human ESCs to intermediate mesoderm. Bioinformatics analysis has unveiled an LHX1 interaction network that positions LHX1 as a master regulator of IM formation. LHX1 regulates IM gene expression through binding to distal elements and its binding is required for the function of IM enhancers. This research is the first to describe a role for a transcription factor in IM lineage specification. Further understanding of the intermediate mesoderm transcriptional fate map should enable higher efficiency kidney differentiations for use in developmental and disease models. This work broadens the understanding of early human embryonic development and provides insight into early mesoderm cell fate decisions.