{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ESRG (also referred to as HESRG) was initially identified as a novel gene that is highly expressed in undifferentiated human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), suggesting a potential role in maintaining pluripotency and self‐renewal."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In addition, an early transient expression of ESRG has been demonstrated during reprogramming processes where its appearance marks a critical intermediate state that is associated with a proliferation pause and linked to cell cycle regulatory mechanisms."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Although ESRG was once considered an important factor for the maintenance of the pluripotent state, targeted deletion experiments showed that ESRG is dispensable for both the primed and naïve pluripotent states, indicating that its function is not essential for the self‐renewal or reprogramming capacities of hESCs."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in stem cell pluripotency, ESRG has been found to interact with cellular proteins—such as COXII—to influence mitochondrial apoptosis in hESCs."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, ESRG is among a set of genes that are expressed at high levels in both ES and reprogrammed cells, setting them apart from differentiated cells; this property makes ESRG a useful marker for detecting residual undifferentiated cells in cell products."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the oncologic context, aberrant expression patterns of ESRG have been identified in certain tumors. For instance, high ESRG expression was observed exclusively in intracranial germinomas and embryonal carcinomas, and in colon cancer ESRG levels were found to distinguish tumor from normal tissues and to correlate negatively with overall patient survival."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, while ESRG may not be critical for the intrinsic maintenance of pluripotency, its distinct and dynamic expression pattern in early stem cell states and during reprogramming, as well as its emerging value as a biomarker in various cancers, highlights its importance as a molecular marker for both basic stem cell research and clinical applications.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ming Zhao, Caiping Ren, Hong Yang, et al. 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