<scp>3D</scp> genome perspective on cell fate determination, organ regeneration, and diseases

Zhong, Huan; Zhang, Jie; Lu, Yong‐Zhong; Hu, Gongcheng; Pan, Guoshun; Yao, Hongjie

doi:10.1111/cpr.13482

Cited by 2 publications

(1 citation statement)

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“…Cell-type specific gene expression which dictates cell fate and function is regulated by transcription factor (TF) networks functioning within 2-D chromatin landscapes organized into 3-D interactomes ( Stadhouders et al, 2018 ; Stadhouders et al, 2019 ; Zhong et al, 2023 ). The 2-D chromatin landscape is manifest from a combination of multiple epigenetic parameters including DNA methylation, histone modifications and non-coding RNAs, all dictating chromatin accessibility ( Bannister and Kouzarides, 2011 ; Guo et al, 2017 ; Razin and Gavrilov, 2021 ; Statello et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Source cell-type epigenetic memory persists in induced pluripotent cells but is lost in subsequently derived germline cells

Lin,

Lehle,

McCarrey

2024

Front. Cell Dev. Biol.

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Introduction: Retention of source cell-type epigenetic memory may mitigate the potential for induced pluripotent stem cells (iPSCs) to fully achieve transitions in cell fate in vitro. While this may not preclude the use of iPSC-derived somatic cell types for therapeutic applications, it becomes a major concern impacting the potential use of iPSC-derived germline cell types for reproductive applications. The transition from a source somatic cell type to iPSCs and then on to germ-cell like cells (GCLCs) recapitulates two major epigenetic reprogramming events that normally occur during development in vivo—embryonic reprogramming in the epiblast and germline reprogramming in primordial germ cells (PGCs). We examined the extent of epigenetic and transcriptomic memory persisting first during the transition from differentiated source cell types to iPSCs, and then during the transition from iPSCs to PGC-like cells (PGCLCs).Methods: We derived iPSCs from four differentiated mouse cell types including two somatic and two germ cell types and tested the extent to which each resulting iPSC line resembled a) a validated ES cell reference line, and b) their respective source cell types, on the basis of genome-wide gene expression and DNA methylation patterns. We then induced each iPSC line to form PGCLCs, and assessed epigenomic and transcriptomic memory in each compared to endogenous PGCs/M-prospermatogonia.Results: In each iPSC line, we found residual gene expression and epigenetic programming patterns characteristic of the corresponding source differentiated cell type from which each was derived. However, upon deriving PGCLCs, we found very little evidence of lingering epigenetic or transcriptomic memory of the original source cell type.Discussion: This result indicates that derivation of iPSCs and then GCLCs from differentiated source cell types in vitro recapitulates the two-phase epigenetic reprogramming that normally occurs in vivo, and that, to a significant extent, germline cell types derived in vitro from pluripotent cells accurately recapitulate epigenetic programming and gene expression patterns corresponding to equivalent endogenous germ cell types, suggesting that they have the potential to form the basis of in vitro gametogenesis as a useful therapeutic strategy for treatment of infertility.

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Section: Introductionmentioning

confidence: 99%

Source cell-type epigenetic memory persists in induced pluripotent cells but is lost in subsequently derived germline cells

Lin,

Lehle,

McCarrey

2024

Front. Cell Dev. Biol.

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3D genome perspective on cell fate determination, organ regeneration, and diseases

Zhong

Zhang

et al. 2023

Cell Proliferation

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The nucleosome is the fundamental subunit of chromatin. Nucleosome structures are formed by the combination of histone octamers and genomic DNA. Through a systematic and precise process of folding and compression, these structures form a 30‐nm chromatin fibre that is further organized within the nucleus in a hierarchical manner, known as the 3D genome. Understanding the intricacies of chromatin structure and the regulatory mode governing chromatin interactions is essential for unravelling the complexities of cellular architecture and function, particularly in relation to cell fate determination, regeneration, and the development of diseases. Here, we provide a general overview of the hierarchical structure of chromatin as well as of the evolution of chromatin conformation capture techniques. We also discuss the dynamic regulatory changes in higher‐order chromatin structure that occur during stem cell lineage differentiation and somatic cell reprogramming, potential regulatory insights at the chromatin level in organ regeneration, and aberrant chromatin regulation in diseases.

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3D genome perspective on cell fate determination, organ regeneration, and diseases

Cited by 2 publications

References 126 publications

Source cell-type epigenetic memory persists in induced pluripotent cells but is lost in subsequently derived germline cells

Source cell-type epigenetic memory persists in induced pluripotent cells but is lost in subsequently derived germline cells

3D genome perspective on cell fate determination, organ regeneration, and diseases

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