{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have revealed that negative elongation factor A (NELFA)—though not LINC01007—plays a crucial role in governing early embryonic cell fate transitions. In mouse embryonic stem cells (ESCs), NELFA is heterogeneously expressed and is linked with the transition of a subset of cells into a 2‑cell (2C)‑like state. This state is characterized by the upregulation of key transcripts such as Dux, a critical regulator of early totipotency. NELFA facilitates this transition through its specific interaction with Top2a, and its activity is further modulated by metabolic cues such as glycolytic flux. Such findings illuminate how NELFA acts as one of the earliest drivers, triggering chromatin and transcriptional changes that diminish ESC-specific enhancer activity and enable the 2C-like fate."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nIn the cardiovascular context, NELFA—also known as Wolf-Hirschhorn syndrome candidate 2—is pivotal for maintaining active and inducible gene expression during cardiac remodeling. Genome-wide occupancy studies in hypertrophied hearts have shown that NELFA preferentially binds active gene promoters, including those of essential cardiac‐enriched genes. Under conditions of pressure-overload hypertrophy, the de novo recruitment of NELFA to inducible promoters correlates with enhanced RNA polymerase II progression and elevated transcript output. This establishes NELFA as an essential factor for facilitating proper transcriptional elongation and ensuring adaptive gene expression in stressed cardiac tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nComplementing these findings in ESCs, additional research demonstrates that overexpression of NELFA robustly enhances the conversion of ESCs into a totipotent-like 2C state and significantly improves somatic cell reprogramming efficiency. Moreover, co-overexpression experiments with Bcl2 not only potentiate the 2C-like program further but, intriguingly, reveal that Bcl2 itself can upregulate endogenous NELFA expression to induce totipotency even in its absence. These synergistic interactions underline the dynamic interplay between apoptotic regulators and transcriptional machinery in establishing and reinforcing a dual cell fate potential."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Zhenhua Hu, Dennis Eng Kiat Tan, Gloryn Chia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Maternal factor NELFA drives a 2C-like state in mouse embryonic stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41556-019-0453-8"}], "href": "https://doi.org/10.1038/s41556-019-0453-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31932739"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31932739"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Saleena Alikunju, Elena Severinova, Zhi Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Acute NelfA knockdown restricts compensatory gene expression and precipitates ventricular dysfunction during cardiac hypertrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Cell Cardiol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yjmcc.2020.04.007"}], "href": "https://doi.org/10.1016/j.yjmcc.2020.04.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32278832"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32278832"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Baojiang Wu, Yanqiu Wang, Xinhua Wei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NELFA and BCL2 induce the 2C-like state in mouse embryonic stem cells in a chemically defined medium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Prolif (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cpr.13534"}], "href": "https://doi.org/10.1111/cpr.13534"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37592709"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37592709"}]}]}]}