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Altered temporal sequence of transcriptional regulators in the generation of human cerebellar granule cells
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Altered temporal sequence of transcriptional regulators in the generation of human cerebellar granule cells
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Altered temporal sequence of transcriptional regulators in the generation of human cerebellar granule cells
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Journal Article
Altered temporal sequence of transcriptional regulators in the generation of human cerebellar granule cells
2021
Overview
Brain development is regulated by conserved transcriptional programs across species, but little is known about the divergent mechanisms that create species-specific characteristics. Among brain regions, human cerebellar histogenesis differs in complexity compared with nonhuman primates and rodents, making it important to develop methods to generate human cerebellar neurons that closely resemble those in the developing human cerebellum. We report a rapid protocol for the derivation of the human ATOH1 lineage, the precursor of excitatory cerebellar neurons, from human pluripotent stem cells (hPSCs). Upon transplantation into juvenile mice, hPSC-derived cerebellar granule cells migrated along glial fibers and integrated into the cerebellar cortex. By Translational Ribosome Affinity Purification-seq, we identified an unexpected temporal shift in the expression of RBFOX3 (NeuN) and NEUROD1, which are classically associated with differentiated neurons, in the human outer external granule layer. This molecular divergence may enable the protracted development of the human cerebellum compared to mice.
Publisher
eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
Subject
/ Antigens, Nuclear - genetics
/ Antigens, Nuclear - metabolism
/ Basic Helix-Loop-Helix Transcription Factors - genetics
/ Basic Helix-Loop-Helix Transcription Factors - metabolism
/ human pluripotent stem cells
/ Humans
/ Labeling
/ Mice
/ Mutation
/ Nerve Tissue Proteins - genetics
/ Nerve Tissue Proteins - metabolism
