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| 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
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| 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.
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| Overall design |
Examine the RNA expression profiles of inducible motor neurons-embryonic stem cells (iMN-ESCs) with or without Dox treatment, with biological duplicates.
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| 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
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| Department |
Biology
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| Street address |
350 New Campus Dr
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| City |
Brockport |
| State/province |
New York |
| ZIP/Postal code |
14420-2997 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (4)
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| GSM869994 |
iMN-ESCs without Dox treatment, rep1 |
| GSM869995 |
iMN-ESCs with Dox treatment, rep1 |
| GSM869996 |
iMN-ESCs without Dox treatment, rep2 |
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| Relations |
| SRA |
SRP010724 |
| BioProject |
PRJNA152319 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE35510_RAW.tar |
3.3 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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