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Klf5 functions as a multi-lineage reprogramming transcription factor

GSE281941 Mus musculus Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing 30 samples Submitted 2025/06/01 Platform GPL24247Platform GPL28330
Summary
The transcription factor Klf5 is indispensable for both embryonic (redundantly with Klf4) and extra-embryonic development during pre-implantation, yet its role in re-establishing these different fates in vitro remains largely unexplored. Here, we demonstrate that in the absence of WNT signaling activation at the beginning, ectopic expression of Klf5 in post-implantation epiblast stem cells (EpiSCs) not only induces naïve pluripotency, but also exclusively drives reprogramming into trophoblast stem cells (TSCs) and primordial germ cells (PGCs) by directly reactivating key lineage-specific determinants. Single-cell transcriptome analysis reveals distinct reprogramming trajectories toward these three fates, alongside a non-reprogramming trajectory that driven by Klf5-mediated BMP signaling activation. Moreover, endogenous Klf5 is crucial for establishing TSC and PGC fates from embryonic stem cells driven by other inducers. Our findings highlight Klf5’s multipotent reprogramming capacity and its pivotal role in early TSC and PGC fate specification, offering new insights into its versatile functions during embryonic development.
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Direct links to NCBI, no account and no request form: the whole study as GSE281941_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 30 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1070353 and SRA study SRP486406. Searching any of these in the dataset finder brings you back here.

Study design
14 conditions, mostly in duplicate
EpiSCs_WT ×2 TSC_WT ×2 ESC_WT ×2 ESC_Klf5_KO ×2 iTSC_Epi2-1_No5 ×2 iTSC_OC-Epi_No2 ×2 iEmpty_D2_LIF ×2 iKlf5_D2_LIF ×2 +8 more

Supports a between-group comparison across 28 samples.

14 replicated groups read from 30 sample titles; they account for 28 of them. Check it against the sample list below before relying on it.

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