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Series GSE226345 Query DataSets for GSE226345
Status Public on Feb 21, 2024
Title Global profiling of Nkx2.2 SD-domain mutant pancreas during development and adulthood compared to transcriptional profiling of SD-domain mutant expressing neural progenitors.
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary The consolidation of unambiguous cell fate commitment relies on the ability of transcription factors (TFs) to exert tissue-specific regulation of complex genetic networks. The mechanisms by which TFs establish such precise control over gene expression, however, have remained elusive—especially in instances where a single TF operates in two or more discrete cellular systems. In this study, we demonstrate that  cell specific functions of NKX2.2 are driven by the highly conserved NK2-Specific Domain (SD). Mutation of the endogenous NKX2.2 SD domain prevents the developmental progression of beta cell precursors into mature, insulin-expressing beta cells, resulting in overt neonatal diabetes. Within the adult beta cell, the SD domain stimulates beta cell performance through the activation and repression of a subset of NKX2.2-regulated transcripts critical for beta cell function. These irregularities in beta cell gene expression may be mediated via SD domain-contingent interactions with components of the nuclear pore complex. In stark contrast to these pancreatic phenotypes, however, the SD domain is entirely dispensable for the development of NKX2.2-dependent cell types within the CNS. Together, these results reveal a previously undetermined mechanism through which NKX2.2 directs disparate transcriptional programs in the pancreas vs. neuroepithelium.
Overall design Examination of total RNA profiles of E15.5 pancreata of wildtype and Nkx2.2SDmut animals, of wildtype and beta-specific Nkx2.2SDmut adult islets, and of mouse ES cell-derived spinal motor neuron progenitors expressing a wildtype copy of Nkx2.2 tagged by FLAG under the control of a doxycycline (DOX) inducible promotor (iNkx2.2), an SD-domain mutant copy of Nkx2.2 tagged by FLAG under the control of a doxycycline (DOX) inducible promotor (iSDmut), or no Nkx2.2 (pMN). Examination of the global DNA binding profile of Nkx2.2 in MIN6 cells. 2-4 replicates are provided for all samples.
Contributor(s) Abarinov V, Levine JA, Churchill AJ, Hopwood B, Dieter C, Guney MA, Wells KL, Friel JM, Guo Y, Hammelman J, Gifford DK, Magnuson MA, Wichterle H, Sussel L
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Submission date Feb 28, 2023
Last update date Feb 21, 2024
Contact name Elena Abarinov
Organization name University of Colorado at Denver
Street address 1775 Aurora Ct
City Aurora
State/province Colorado
ZIP/Postal code 80045
Country USA
Platforms (2)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (27)
GSM7073682 pMN_EA1_GTTTCG_L002_R1_001 [pMN_CTRL_1]
GSM7073683 pMN_EA5_ATTCCT_L002_R1_001 [pMN_CTRL_2]
GSM7073684 pMN_EA13_ACTGAT_L004_R1_001 [pMN_CTRL_3]
BioProject PRJNA939831

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE226345_Adult_pancreas_FPKM.txt.gz 664.3 Kb (ftp)(http) TXT
GSE226345_Adult_pancreas_RNAseq_SDmut_vs_CTRL_SigGenes.txt.gz 438.0 Kb (ftp)(http) TXT
GSE226345_Adult_pancreas_RNAseq_readcounts.txt.gz 362.9 Kb (ftp)(http) TXT
GSE226345_E15.5_pancreas_RNAseq_Normalized_readcounts.txt.gz 932.6 Kb (ftp)(http) TXT
GSE226345_E15.5_pancreas_RNAseq_SigGenes.txt.gz 690.5 Kb (ftp)(http) TXT
GSE226345_E15.5_pancreas_RNAseq_readcounts.txt.gz 772.5 Kb (ftp)(http) TXT
GSE226345_Neural_progenitors_RNAseq_FPKM.txt.gz 726.1 Kb (ftp)(http) TXT
GSE226345_Neural_progenitors_RNAseq_SigGenes.txt.gz 83.2 Kb (ftp)(http) TXT
GSE226345_Neural_progenitors_RNAseq_readcounts.txt.gz 440.8 Kb (ftp)(http) TXT
GSE226345_Nkx2.2_logCPM_final_sites.txt.gz 64.3 Kb (ftp)(http) TXT
GSE226345_RawCounts_Nkx2.2_all_GEM_events.txt.gz 82.0 Kb (ftp)(http) TXT
GSE226345_betaSDmut_vs_betaKO_Nkx2.2_bound_SigGenes.txt.gz 227.3 Kb (ftp)(http) TXT
GSE226345_betaSDmut_vs_betaKO_vs_CTRL_SigGenes.txt.gz 696.8 Kb (ftp)(http) TXT
GSE226345_readme.txt 1.5 Kb (ftp)(http) TXT
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