Cell-Cycle-Specific Autoencoding Improves Cluster Analysis of Cycling Cardiomyocytes.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38587452", "kind": "science-record", "revision": 4, "content_hash": "sha256:cd0c76307730803b908904d73ca81585d3aa431c0ac723b2eecd7d011bcac9af", "created_at": "2026-11-01T19:20:33Z", "updated_at": "2026-11-01T22:11:37Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Cell-Cycle-Specific Autoencoding Improves Cluster Analysis of Cycling Cardiomyocytes.", "doi": "10.1093/stmcls/sxae016", "pmid": "38587452", "authors": ["Thanh Nguyen", "Yuji Nakada", "Yalin Wu", "Jianli Zhao", "Daniel J Garry", "Hesham Sadek", "Jianyi Zhang"], "journal": "Stem cells (Dayton, Ohio)", "year": 2024, "abstract": "BACKGROUND: Our previous analyses of cardiomyocyte single-nucleus RNA sequencing (snRNAseq) data from the hearts of fetal pigs and pigs that underwent apical resection surgery on postnatal day (P) 1 (ARP1), myocardial infarction (MI) surgery on P28 (MIP28), both ARP1 and MIP28 (ARP1MIP28), or controls (no surgical procedure or CTL) identified 10 cardiomyocyte subpopulations (clusters), one of which appeared to be primed to proliferate in response to MI. However, the clusters composed of primarily proliferating cardiomyocytes still contained noncycling cells, and we were unable to distinguish between cardiomyocytes in different phases of the cell cycle. Here, we improved the precision of our assessments by conducting similar analyses with snRNAseq data for only the 1646 genes included under the Gene Ontology term \"cell cycle.\"\nMETHODS: Two cardiac snRNAseq datasets, one from mice (GEO dataset number GSE130699) and one from pigs (GEO dataset number GSE185289), were evaluated via our cell-cycle-specific analytical pipeline. Cycling cells were identified via the co-expression of 5 proliferation markers (AURKB, MKI67, INCENP, CDCA8, and BIRC5).\nRESULTS: The cell-cycle-specific autoencoder (CSA) algorithm identified 7 cardiomyocyte clusters in mouse hearts (mCM1 and mCM3-mCM8), including one prominent cluster of cycling cardiomyocytes in animals that underwent MI or Sham surgery on P1. Five cardiomyocyte clusters (pCM1, pCM3-pCM6) were identified in pig hearts, 2 of which (pCM1 and pCM4) displayed evidence of cell cycle activity; pCM4 was found primarily in hearts from fetal pigs, while pCM1 comprised a small proportion of cardiomyocytes in both fetal hearts and hearts from ARP1MIP28 pigs during the 2 weeks after MI induction, but was nearly undetectable in all other experimental groups and at all other time points. Furthermore, pseudotime trajectory analysis of snRNAseq data from fetal pig cardiomyocytes identified a pathway that began at pCM3, passed through pCM2, and ended at pCM1, whereas pCM3 was enriched for the expression of a cell cycle activator that regulates the G1/S phase transition (cyclin D2), pCM2 was enriched for an S-phase regulator (CCNE2), and pCM1 was enriched for the expression of a gene that regulates the G2M phase transition and mitosis (cyclin B2). We also identified 4 transcription factors (E2F8, FOXM1, GLI3, and RAD51) that were more abundantly expressed in cardiomyocytes from regenerative mouse hearts than from nonregenerative mouse hearts, from the hearts of fetal pigs than from CTL pig hearts, and from ARP1MIP28 pig hearts than from MIP28 pig hearts during the 2 weeks after MI induction.\nCONCLUSIONS: The CSA algorithm improved the precision of our assessments of cell cycle activity in cardiomyocyte subpopulations and enabled us to identify a trajectory across 3 clusters that appeared to track the onset and progression of cell cycle activity in cardiomyocytes from fetal pigs.", "claims": [{"id": "claim-method", "statement": "The architecture of this cell-cycle –specific autoencoder (CSA; Supplementary Fig. S3) consisted of input and output (synthetic) layers, each with 1646 nodes, and a central embedded layer with 10 nodes.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38587452", "locator": "sections[8] \"Autoencoder and Clustering\" paragraph 2", "quote": "The architecture of this cell-cycle –specific autoencoder (CSA; Supplementary Fig. S3) consisted of input and output (synthetic) layers, each with 1646 nodes, and a central embedded layer with 10 nodes."}], "state": "complete"}, {"id": "claim-data-access", "statement": "This work reused the single-nuclei sequencing data from Gene Expression Omnibus database, accession numbers GSE130699 and GSE185289.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38587452", "locator": "sections[26] \"Data Availability\" paragraph 2", "quote": "This work reused the single-nuclei sequencing data from Gene Expression Omnibus database, accession numbers GSE130699 and GSE185289."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The CSA algorithm improved the precision of the assessments of cell cycle activity in cardiomyocyte subpopulations and enabled the identification of a trajectory across 3 clusters that appeared to track the onset and progression of cell cycle activity in cardiomyocytes from fetal pigs.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38587452", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "The CSA algorithm improved the precision of our assessments of cell cycle activity in cardiomyocyte subpopulations and enabled us to identify a trajectory across 3 clusters that appeared to track the onset and progression of cell cycle activity in cardiomyocytes from fetal pigs."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The CSA algorithm improved the precision of the assessments of cell cycle activity in cardiomyocyte subpopulations and enabled the identification of a trajectory across 3 clusters that appeared to track the onset and progression of cell cycle activity in cardiomyocytes from fetal pigs.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:38587452"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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