RT Journal Article
SR Electronic
T1 Single cell RNA-Seq analysis identifies molecular mechanisms controlling hypothalamic patterning and differentiation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 657148
DO 10.1101/657148
A1 Dong Won Kim
A1 Parris Whitney Washington
A1 Zoe Qianyi Wang
A1 Sonia Lin
A1 Changyu Sun
A1 Lizhi Jiang
A1 Seth Blackshaw
YR 2019
UL http://biorxiv.org/content/early/2019/06/07/657148.abstract
AB The hypothalamus is a central regulator of many innate behaviors that are essential for survival, but the molecular mechanisms controlling hypothalamic patterning and cell fate specification remain poorly understood. To identify genes that control hypothalamic development, we have used single-cell RNA sequencing (scRNA-Seq) to profile mouse hypothalamic gene expression across 12 developmental time points between embryonic day 10 and postnatal day 45. This identified genes that delineated clear developmental trajectories for all major hypothalamic cell types, and readily distinguished major regional subdivisions of the developing hypothalamus. We show that this approach can rapidly and comprehensively characterize mutants that have altered hypothalamic patterning, and in doing so, have identified multiple genes that simultaneously repress posterior hypothalamic identity while promoting prethalamic identity. This result supports a modified columnar model of organization for the diencephalon, where prethalamus and hypothalamus are situated in adjacent dorsal and ventral domains of the anterior diencephalon. These data serve as a resource for further studies of hypothalamic development, physiology and dysfunction.