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SRX24824015: GSM8310813: SIGAB2. replicate 1, scRNAseq; Xenopus laevis; RNA-Seq
4 ILLUMINA (Illumina HiSeq 2500) runs: 173M spots, 22G bases, 6.5Gb downloads

External Id: GSM8310813_r1
Submitted by: Hoermanseder Lab, Institute of Epigenetics and Stem Cells, Helmholtz Center Munich
Study: Single-cell RNA-sequencing of in vitro fertilized and nuclear transfer embryos
show Abstracthide Abstract
Somatic cell nuclear transfer and transcription factor overexpression can induce reprogramming of somatic cells, whereby one cell fate is changed into another cell fate of choice. Yet the efficiency of this process for generating functional cells is low, limiting their therapeutic applications. The persistence of transcriptional memory from the cell's prior identity is thought to be a major hindrance to effective reprogramming and differentiation to functional cell types. To explore the effects of transcriptional memory on cell fate specification of reprogrammed cells, we analyzed epidermal tissue development in nuclear transfer embryos derived from endoderm nuclei. Our findings reveal variations in the success rate of differentiation to functional cells across cell types in cloned embryos. While some cell types, such as goblet cells, differentiated normally, a specific subset of cells resisted cell fate reprogramming, adopting a new endoderm-like state and disrupting normal body patterning. Furthermore, inefficient transcriptional reprogramming correlated with reduced basal stem cell populations, faulty differentiation of basal stem cell-derived fates, and increased cell death in the epidermis of cloned embryos. Crucially, we identified that the memory of active transcriptional states linked to key endoderm transcription factors plays a significant role in these issues. Mimicking active state transcriptional memory of these genes through the forced expression of Sox17b and Foxa4 in the epidermis of fertilized embryos produced the same defects. On the contrary, reducing transcriptional memory by interfering with the expression of Sox17b led to the rescue of observed epidermal defects. In summary, our study suggests that transcriptional memory tends to persist predominantly in specific reprogrammed cell types, hindering their differentiation into functional cells and embryonic structures. This underscores the critical need to assess and reduce transcriptional memory from the previous somatic identity during reprogramming, to efficiently generate functional cell types for therapeutic applications. Overall design: Ectodermal explants from 5 In vitro fertilized (IVF) and 5 nuclear transfer (NT) Xenopus Laevis embryos at stage 12 from two independent experiments were subjected to single-cell RNA sequencing
Sample: SIGAB2. replicate 1, scRNAseq
SAMN41708802 • SRS21537143 • All experiments • All runs
Organism: Xenopus laevis
Library:
Name: GSM8310813
Instrument: Illumina HiSeq 2500
Strategy: RNA-Seq
Source: TRANSCRIPTOMIC SINGLE CELL
Selection: cDNA
Layout: PAIRED
Construction protocol: Ectodermal explants were isolated from IVF and NT embryos of stage 12 and shortly washed in Newport 2.0 dissociation buffer (100 mM sodium isethionate, 20 mM sodium pyrophosphate, 10 mM CAPS, 20 mM glucose, pH10.5 adjusted by NaOH) to remove calcium ions. Ectodermal explants were transferred into fresh dissociation buffer in BSA coated low bind microcentrifuge tubes and incubated for 30min at 18°C with agitation. During the period of incubation, tubes were inverted several times. Resulting single cell suspensions were resuspended in PBS-BSA solution and filtered through 30 µm cell strainers. Cells were washed 3-times with 1 ml PBS-BSA, counted and analyzed for viability. 2500 cells with viability more than 95% and not detectable RNA in supernatant were submitted for library preparation. Libraries were constructed according to the manufacturer's instructions (single-cell 3' v2 and v3 protocols, 10x Genomics). GCs were resuspendend in the master mix and loaded together with partitioning oil and gel beads into the chip to generate the gel bead-in-emulsion (GEM). The poly-A RNA from the cell lysate contained in every single GEM was retrotranscribed to cDNA, which contains an Illumina R! primer sequence, Unique Molecular Identifier (UMI) and the 10x barcode. The pooled barcoded cDNA was then cleaned up with Silane DynaBeads, amplified by PCR and the appropriate sized fragments were selected with SPRIselect reagent for subsequent library construction. During the library construction Illumina R2 primer sequence, paired-end constructs with P5 and P7 sequences and a sample index were added.
Runs: 4 runs, 173M spots, 22G bases, 6.5Gb
Run# of Spots# of BasesSizePublished
SRR2930705250,121,9806.4G1.9Gb2024-07-01
SRR2930705342,963,5645.5G1.6Gb2024-07-01
SRR2930705437,344,9814.7G1.4Gb2024-07-01
SRR2930705542,547,8775.4G1.6Gb2024-07-01

ID:
33158235

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