Defining the nature of human pluripotent stem cell-derived interneurons via single-cell analysis

被引：12

作者：

Allison, Thomas ^{[4
]}

Langerman, Justin ^{[4
]}

Sabri, Shan ^{[4
,10
]}

Otero-Garcia, Marcos ^{[7
]}

Lund, Andrew ^{[1
]}

Huang, John ^{[4
]}

Wei, Xiaofei ^{[12
]}

Samarasinghe, Ranmal A. ^{[2
,11
,12
,13
]}

Polioudakis, Damon ^{[5
,6
]}

Mody, Istvan ^{[12
]}

Cobos, Inma ^{[8
]}

Novitch, Bennett G. ^{[2
,11
,13
]}

Geschwind, Daniel H. ^{[5
,6
,7
,13
]}

Plath, Kathrin ^{[2
,3
,4
,9
,10
]}

Lowry, William E. ^{[1
,2
,3
,9
,13
]}

机构：

[1] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Broad Stem Cell Ctr Regenerat Med, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, Mol Biol Inst, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, David Geffen Sch Med, Program Neurogenet, Dept Neurol, Los Angeles, CA 90095 USA

[6] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA

[7] Univ Calif Los Angeles, Semel Inst, Ctr Autism Res & Treatment, Los Angeles, CA USA

[8] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA

[9] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA

[10] Univ Calif Los Angeles, Bioinformat PhD Program, Los Angeles, CA 90095 USA

[11] Univ Calif Los Angeles, Dept Neurobiol, Los Angeles, CA USA

[12] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA

[13] Univ Calif Los Angeles, Intellectual & Dev Disabil Res Ctr, Los Angeles, CA 90095 USA

来源：

STEM CELL REPORTS | 2021年 / 16卷 / 10期

关键词：

FUNCTIONAL MATURATION; CORTICAL INTERNEURONS; MUTATIONS CAUSE; ICF SYNDROME; DIVERSITY; NEURONS; RNA; MECHANISMS; BRAIN; SPECIFICATION;

D O I：

10.1016/j.stemcr.2021.08.006

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

The specification of inhibitory neurons has been described for the mouse and human brain, and many studies have shown that pluripotent stem cells (PSCs) can be used to create interneurons in vitro. It is unclear whether in vitro methods to produce human interneurons generate all the subtypes found in brain, and how similar in vitro and in vivo interneurons are. We applied single-nuclei and single-cell transcriptomics to model interneuron development from human cortex and interneurons derived from PSCs. We provide a direct comparison of various in vitro interneuron derivation methods to determine the homogeneity achieved. We find that PSC-derived interneurons capture stages of development prior to mid-gestation, and represent a minority of potential subtypes found in brain. Comparison with those found in fetal or adult brain highlighted decreased expression of synapse-related genes. These analyses highlight the potential to tailor the method of generation to drive formation of particular subtypes.

引用

页码：2548 / 2564

页数：17

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