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Single-cell RNA sequencing data of stem cell-derived microfluidic human embryoids, NODAL-KO human embryoids and chimpanzee embryoids

ABSTRACT: Transcriptome at the single-cell level of a human embryoid model, which recapitulates aspects of lineage diversification and three-dimensional tissue architecture of the human embryo from the implantation to the onset of gastrulation, was profiled at different time points. Similarly, chimpanzee embryoids were generated and profiled to reveal transcriptome dynamics during the early post-implantation chimpanzee development. Our comparative transcriptome analyses reveal a critical role of NODAL signaling in human mesoderm specification, which is functionally validated by generating embryoids with NODAL-knockout (KO) hPSCs.

ORGANISM(S): Homo sapiens Pan troglodytes

PROVIDER: GSE185643 | GEO | 2021/10/13

REPOSITORIES: GEO

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Project description:The biology underlying nodal metastasis is poorly understood. Transcriptome profiling has helped to characterize both primary tumors seeding nodal metastasis and the metastasis themselves. The interpretation of these data, however, is not without ambiguities. Here we profiled the transcriptomes of 17 papillary thyroid cancer (PTC) nodal metastases, associated primary tumors and primary tumors from N0 patients. We also included patient-matched normal thyroid and lymph node samples as controls to address some limits of previous studies. We found that the transcriptomes of patient-matched primary tumors and metastases were more similar than of unrelated metastases/primary pairs, a result also reported in other organ systems, and that part of this similarity reflected patient background. We found that the comparison of patient-matched primary tumors and metastases was heavily confounded by the presence of lymphoid tissues in the metastasis samples. An original data adjustment procedure was developed to circumvent this problem. It revealed a differential expression of stroma-related gene expression signatures also regulated in other organ systems. The comparison of N0 vs. N+ primary tumors uncovered a signal irreproducible across independent PTC datasets. This signal was also detectable when comparing the normal thyroid tissues adjacent to N0 and N+ tumors, suggesting a cohort specific bias also likely to be present in previous studies with similar statistical power. Classification of N0 vs. N+ yielded an accuracy of 63%, but additional statistical controls not presented in previous studies, revealed that this is likely to occur by chance alone. To address this issue, we used large datasets from The Cancer Genome Atlas and showed that N0 vs. N+ classification rates could not be reached randomly for most cancers. Yet, it was significant, but of limited accuracy (<70%) for thyroid, breast and head and neck cancers. We profiled the transcriptomes of 11 primary PTCs with no detectable nodal invasion, 17 primary PTCs with nodal invasion and 17 patient-matched nodal metastases. We also profiled a number of control samples. These included 24 patient-matched normal thyroid tissues (11 from N0, 13 from N+ patients), and 4 normal lymph nodes; technical and biological replicates including additional nodal metastasis for 3 patients, adjacent blocks for 5 primary tumors, 4 normal thyroid tissues and 1 nodal metastasis.

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Single-cell RNA sequencing data of stem cell-derived microfluidic human embryoids, NODAL-KO human embryoids and chimpanzee embryoids

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