Induction of human Somatostatin and Parvalbumin neurons by expressing a single transcription factor LIM Homeobox 6
- Nanjing Medical University, China
- ShanghaiTech University, China
- Fudan University, China
- Chinese Academy of Sciences, China
Abstract
Human GABAergic interneurons (GIN) are implicated in normal brain function as well as numerous mental disorders. However, generation of functional human GIN subtypes from human pluripotent stem cells (hPSCs) has not been established. By expressing LHX6, a transcriptional factor critical for GIN development, we have induced hPSCs to GINs, including somatostatin (SST, 29%) and parvalbumin (PV, 21%) neurons. Our RNAseq results also confirmed alteration of GINs identity with the overexpression of LHX6. Five months after transplantation into the mouse brain, the human GABA precursors generated increased population of SST and PV neurons by overexpressing LHX6. Importantly, the grafted human GINs exhibited functional electrophysiological properties and even fast-spiking like action potentials. Thus, expression of the single transcription factor LHX6 under our GIN differentiation condition is sufficient to robustly induce human PV and SST subtypes.
Data availability
Sequencing data have been deposited in GEO under accession codesGSE114553. All data generated or analysed during this study are included in the manuscript and supporting files.
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Induction of human SST and PV neurons by expressing a single transcription factor LHX6Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE114553).
Article and author information
Author details
Funding
National Natural Science Foundation of China (81471301)
- Yan Liu
National Key Research and Development Program of China (2016YFC1306703)
- Yan Liu
Jiangsu Outstanding Young Investigator Program (BK20160044)
- Yan Liu
ShanghaiTech Start-up Foundation
- Shuijin He
Postgraduate Research and Practice Innovation Program of Jiangsu Province
- Fang Yuan
Strategic Priority Research Program of the Chinese Academy of the Chinese Academy of Sciences (XDA16010306)
- Yan Liu
National Natural Science Foundation of China (31671063)
- Yan Liu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: SCID mice were purchased from the Model Animal Research Center of Nanjing University. All of the animal experiments followed standard experimental protocols and were approved by the Animal Care and Use Committee at Nanjing Medical University(IACUC-1601129).
Human subjects: H9 cell line was purchased from Wicell Agreeement (NO.16-W0060)For ips cell line, verbal and written consent was obtained from the person.The study was approved by the ethic community of Nanjing Medical University[(2017）NO.217].
Copyright
© 2018, Yuan et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Induction of human Somatostatin and Parvalbumin neurons by expressing a single transcription factor LIM Homeobox 6
eLife 7:e37382.
https://doi.org/10.7554/eLife.37382
Further reading
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- Developmental Biology
- Stem Cells and Regenerative Medicine
Niches are often found in specific positions in tissues relative to the stem cells they support. Consistency of niche position suggests that placement is important for niche function. However, the complexity of most niches has precluded a thorough understanding of how their proper placement is established. To address this, we investigated the formation of a genetically tractable niche, the Drosophila Posterior Signaling Center (PSC), the assembly of which had not been previously explored. This niche controls hematopoietic progenitors of the lymph gland (LG). PSC cells were previously shown to be specified laterally in the embryo, but ultimately reside dorsally, at the LG posterior. Here, using live-imaging, we show that PSC cells migrate as a tight collective and associate with multiple tissues during their trajectory to the LG posterior. We find that Slit emanating from two extrinsic sources, visceral mesoderm and cardioblasts, is required for the PSC to remain a collective, and for its attachment to cardioblasts during migration. Without proper Slit-Robo signaling, PSC cells disperse, form aberrant contacts, and ultimately fail to reach their stereotypical position near progenitors. Our work characterizes a novel example of niche formation and identifies an extrinsic signaling relay that controls precise niche positioning.
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- Developmental Biology
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