GEO series
Spatiotemporal control of SMARCA5 by a MAPK-RUNX1 axis distinguishes mutant KRAS-driven pancreatic malignancy from tissue regeneration (RNA-Seq)
GSE248947
Mus musculus; Homo sapiens
Expression profiling by high throughput sequencing
28 samples
Submitted 2025/07/01
Platform GPL24247Platform GPL28330Platform GPL29480
Summary
De-differentiation or trans-differentiation is a common response to injury in many tissues, and the processes predispose cells to cancer. Acute pancreatitis-induced acinar-to-ductal metaplasia (ADM) is similar to pancreatic ductal adenocarcinoma (PDAC) at both the chromatin level and gene expression level. Mutant KRAS induces chromatin remodeling activities required for both regeneration and tumorigenesis at the peak of ADM, and it blocks regeneration. We show that chromatin remodeler SMARCA5 (SNF2H) can promotes the regeneration defects caused by mutant KRAS by maintaining chromatin accessibility at regions specifically required for malignancy. Mechanistically, regeneration-related chromatin remodeling activities are shared between wild-type and mutant KRAS and they occur very early upon pancreatitis, while the malignancy-related chromatin regions become accessible much later. The activity of SMARCA5 is controlled spatiotemporally by transcription factor RUNX1, which is only accumulated at sufficient levels at late ADM lock-in stage. Finally, we show that the malignancy regulation activity of SMARCA5 is different from its general function in CTCF recruitment. In summary, we have identified a specific function of a general chromatin remodeler that is precisely controlled during acinar cell trans-differentiation to separate malignancy from tissue regeneration.
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE248947_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 28 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1046497 and SRA study SRP474954. Searching any of these in the dataset finder brings you back here.
Study design
10 conditions, mostly in duplicate
RNA_D7_Rosa ×5
RNA_D7_Smarca5 ×2
RNA_D7_Runx1 ×2
RNA_tumor_Rosa ×2
RNA_tumor_Smarca5 ×2
PDCC,shRUNX1, ×2
PDCC,shScramble, ×2
PDCC,shSMARCA5, ×2
+7 more
Supports a case/control comparison: 6 samples read as cases, 4 as controls.
10 replicated groups read from 28 sample titles; they account for 23 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM7923457 RNA_D7_Rosa_724
- GSM7923458 RNA_D7_Rosa_805
- GSM7923459 RNA_D7_Smarca5_722
- GSM7923460 RNA_D7_Smarca5_770
- GSM7923461 RNA_D7_Rosa_22
- GSM7923462 RNA_D7_Rosa_55
- GSM7923463 RNA_D7_Rosa_738
- GSM7923464 RNA_D7_Runx1_737
- GSM7923465 RNA_D7_Runx1_741
- GSM7923466 RNA_tumor_Rosa_953
- GSM7923467 RNA_tumor_Rosa_993
- GSM7923468 RNA_tumor_Smarca5_888
- GSM7923469 RNA_tumor_Smarca5_893
- GSM8795432 PDCC,shRUNX1,rep1
- GSM8795433 PDCC,shRUNX1,rep2
- GSM8795434 PDCC,shScramble,rep1
- GSM8795435 PDCC,shScramble,rep2
- GSM8795436 PDCC,shSMARCA5,rep1
- GSM8795437 PDCC,shSMARCA5,rep2
- GSM8795438 PDCC,DMSO,rep1
- GSM8795439 PDCC,DMSO,rep2
- GSM8795440 PDCC,GSK2801,rep1
- GSM8795441 PDCC,GSK2801,rep2
- GSM8795442 tumor,Rosa,211
- GSM8795443 tumor,Smarca5,212
- GSM8795444 D7,Rosa,33
- GSM8795445 D7,Runx1,27
- GSM8795446 D7,Smarca5,33
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