Inferring Regulatory Programs Governing Region Specificity of Neuroepithelial Stem Cells During Early Hindbrain and Spinal Cord Development

Overview

Journal Cell Syst

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2019 Jul 15

PMID 31302154

Citations 9

Authors

Deborah Chasman

Nisha Iyer

Alireza Fotuhi Siahpirani

Maria Estevez Silva

Ethan Lippmann

Brian McIntosh

Mitchell D Probasco

Peng Jiang

Ron Stewart

James A Thomson

Randolph S Ashton

Sushmita Roy

Affiliations

Soon will be listed here.

Abstract

Neuroepithelial stem cells (NSC) from different anatomical regions of the embryonic neural tube's rostrocaudal axis can differentiate into diverse central nervous system tissues, but the transcriptional regulatory networks governing these processes are incompletely understood. Here, we measure region-specific NSC gene expression along the rostrocaudal axis in a human pluripotent stem cell model of early central nervous system development over a 72-h time course, spanning the hindbrain to cervical spinal cord. We introduce Escarole, a probabilistic clustering algorithm for non-stationary time series, and combine it with prior-based regulatory network inference to identify genes that are regulated dynamically and predict their upstream regulators. We identify known regulators of patterning and neural development, including the HOX genes, and predict a direct regulatory connection between the transcription factor POU3F2 and target gene STMN2. We demonstrate that POU3F2 is required for expression of STMN2, suggesting that this regulatory connection is important for region specificity of NSCs.

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