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Single cell transcriptome of regional human embryonic stem cell-derived dorsal and ventral neurons from the hindbrain and spinal cord

ABSTRACT: We generated single RNA-seq data to measure transcriptional profiles of 14 hESC-derived neuronal populations, representing distinct regions along the dorsoventral and rostrocaudal axes of the developing hindbrain and human spinal cord. These cells are differentiated using a modular protocol that first induces collinear activation of region-specific HOX genes by exposure to FGF8 and Wnt signaling (Lippmann et al, 2015 PMID:25843047). By transitioning to media containing retinoic acid (RA), SB-431542, and LDN-193189, we generate dedicated posterior central nervous system progenitors with unique rostrocaudal identities. Dorsal patterning by BMP4 or ventral patterning by Sonic hedgehog agonists (smoothened agonist (SAG) and Purmorphamine (Pur)), followed by DAPT gave rise to somatosensory or locomotor neuronal cultures. In total we recovered the transcriptomes of 46,959 cells. Analysis verified expression of increasingly caudal HOX paralogs that could be correlated to hindbrain (HOX1-5; H24, H48, and H72), cervical (HOX1-8; H72 and H120), thoracic (HOX1-9; H168), and thoracolumbar (HOX1-11; H216 and H216R) spinal regions. The dataset also includes representation from major cardinal neuron types. Comparison with existing mouse and human datasets revealed the overall similarity between in vitro-derived and in vivo neurons. Moreover, we detect hundreds of transcriptional markers within region-specific neuronal phenotypes, enabling discovery of novel gene expression patterns along the human developmental axes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE186697 | GEO | 2022/07/28

REPOSITORIES: GEO

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