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Mitochondrial SHMT2 is a crucial therapeutic target in dedifferentiated thyroid cancer (2nd study)

GSE223765 Homo sapiens (human) Single-cell RNA-seq 65 samples Submitted 2024/07/01 Platform GPL18573
At a glance

Single-cell RNA-seq · human · 65 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism
Homo sapiens (human)
Topic
Thyroid cancerThis series is part of our curated briefing on it.
Samples
65 samples: 65 samples, each with a distinct title — no replicated groupsGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Single Cell Analysis of Human Thyroid Reveals the Transcriptional Signatures of AgingEndocrinology · 2023
Summary (written by the submitters)
The roles of the serine/glycine metabolic pathway (SGP) have recently been evident in certain types of tumor physiology; however, the pathological relevance of SGP in undifferentiated thyroid cancer remains unexplored. Herein, we employed a comparative transcriptome analysis of bulk RNA sequencing coupled with single-cell RNA sequencing, showing that the high expression of SHMT2 and MTHFD2 is tightly associated with a low thyroid differentiation score (TDS) and poor clinical features in thyroid cancer.
Read the full summary ↓
In addition, unique metabolic reprogramming of SGP-relevant pathways in dedifferentiated cancer cells, and a distinct trajectory of a subpopulation of tumor cells with a high mitochondrial one-carbon pathway was observed. More importantly, such dramatic changes are functionally relevant, as inhibition of SHMT2 significantly compromises mitochondrial respiration and decreases tumor size by upregulating TDS markers. Taken together, our results highlight the importance of the mitochondrial one-carbon pathway, including SGP, in undifferentiated thyroid cancer and suggest that SHMT2 is a novel therapeutic target. RNA-seq data of 65 fresh frozen normal tissues were generated. Total RNA was isolated by RNeasy Mini Kit (Qiagen, CA, USA), according to the manufacturer's protocol. The quality and integrity of the RNA were confirmed by agarose gel electrophoresis and ethidium bromide staining, followed by visual examination under ultraviolet light. Sequencing library was prepared using TruSeq RNA Sample Preparation kit v2 (Illumina, CA, USA) according to the manufacturer’s protocols. Briefly, mRNA was purified from total RNA using poly-T oligo-attached magnetic beads, fragmented, and converted into cDNAs. Then, adapters were ligated and the fragments were amplified on a PCR. Sequencing was performed in paired end reads (2x75 bp) using NextSeq 500 platform (Illumina).
Published in
Single Cell Analysis of Human Thyroid Reveals the Transcriptional Signatures of Aging
Hong Y, Kim HJ, Park S et al. · Endocrinology 2023 · PMID 36791033 · doi:10.1210/endocr/bqad029
This dataset
Open GSE223765 in finder → Find more human RNA-seq datasets → Thyroid cancer landscape →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE223765_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA928356 and SRA study SRP419238. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 36791033) ↗
Study design
65 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 65 sample titles: 65 distinct titles with little repetition. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

+ 25 more — browse all 65 samples with per-sample file links →

More Thyroid cancer datasets

Search all human RNA-seq datasets in GEO →

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.