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Series GSE35510 Query DataSets for GSE35510
Status Public on Feb 03, 2012
Title Isl1-Lhx3 fusion specifies motor neuron fate by inducing motor neuron genes and concomitantly suppressing the interneuron programs
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Combinatorial transcription codes generate the myriad of cell types during development, and thus likely provide crucial insights into directed differentiation of stem cells to a specific cell type. The LIM-complex composed of Isl1 and Lhx3 directs the specification of spinal motor neurons (MNs) in embryos. Here, we report that Isl1-Lhx3, a LIMcomplex-mimicking fusion, induces a signature of MN transcriptome and concomitantly suppresses interneuron differentiation programs, thereby serving as a potent and specific inducer of MNs in stem cells. We show that an equimolar ratio of Isl1 and Lhx3 and the LIM-domain of Lhx3 are crucial for generating MNs without upregulating interneuron genes. These led us to design Isl1-Lhx3, which maintains the desirable 1:1 ratio of Isl1 and Lhx3 and the LIM-domain of Lhx3. Isl1-Lhx3 drives MN differentiation with high specificity and efficiency in the spinal cord and embryonic stem cells, bypassing the need for sonic hedgehog. RNA-seq analysis revealed that Isl1-Lhx3 induces the expression of a battery of MN genes that control various functional aspects of MNs, while suppressing key interneuron genes. Our studies uncover a highly efficient method for directed MN generation and MN gene networks. Our results also demonstrate a general strategy of utilizing embryonic transcription complexes for producing specific cell types from stem cells.
Overall design Examine the RNA expression profiles of inducible motor neurons-embryonic stem cells (iMN-ESCs) with or without Dox treatment, with biological duplicates.
Contributor(s) Lee S, Shen R, Lee S
Citation(s) 22343290
Submission date Feb 02, 2012
Last update date May 15, 2019
Contact name Rongkun Shen
Organization name SUNY Brockport
Department Biology
Street address 350 New Campus Dr
City Brockport
State/province New York
ZIP/Postal code 14420-2997
Country USA
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (4)
GSM869994 iMN-ESCs without Dox treatment, rep1
GSM869995 iMN-ESCs with Dox treatment, rep1
GSM869996 iMN-ESCs without Dox treatment, rep2
SRA SRP010724
BioProject PRJNA152319

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Supplementary file Size Download File type/resource
GSE35510_RAW.tar 3.3 Mb (http)(custom) TAR (of TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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