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Epigenetics as “conductor” in “orchestra” of pluripotent states

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Abstract

Pluripotent character is described as the potency of cells to differentiate into all three germ layers. The best example to reinstate the term lies in the context of embryonic stem cells (ESCs). Pluripotent ESC describes the in vitro status of those cells that originate during the complex process of embryogenesis. Pre-implantation to post-implantation development of embryo embrace cells with different levels of stemness. Currently, four states of pluripotency have been recognized, in the progressing order of “naïve,” “poised,” “formative,” and “primed.” Epigenetics act as the “conductor” in this “orchestra” of transition in pluripotent states. With a distinguishable gene expression profile, these four states associate with different epigenetic signatures, sometimes distinct while otherwise overlapping. The present review focuses on how epigenetic factors, including DNA methylation, bivalent chromatin, chromatin remodelers, chromatin/nuclear architecture, and microRNA, could dictate pluripotent states and their transition among themselves.

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Abbreviations

3D:

3-Dimension

5hmC:

5-Hydroxy methylcytosine

5mC:

5-Methylcytosine

ABCG2:

ATP-binding cassette subfamily G member 2

AK028326:

Retinal non-coding, RNA 2 (RNCR2), Gomafu, Miat

AK141205:

Cis-antisense to C18ORF22 homolog

BAF:

BRG1-associated factor complex

BRG1:

Brahma-related gene-1

BRM:

Brahma

CAPS2:

Calcyphosine 2

Cc:

Coiled coil

CCDC144NL-AS1:

Coiled-coil domain containing 144 family, N-terminal like antisense RNA 1

CHD:

Chromodomain helicase DNA-binding

ChEP:

Chromain enrichment for proteomics

ChIP-seq:

Chromatin immunoprecipitation-sequencing

CLDN4:

Claudin 4

CTCF:

CCCTC-binding factor

DGCR8:

DiGeorge syndrome critical region gene 8

DIDO1:

Death inducer-obliterator 1

DNMT:

DNA methyltransferase

DPPA3:

Developmental pluripotency-associated 3

DROSHA:

Double-stranded RNA-specific endoribonuclease

DUSP27:

Dual-specificity phosphatase 27

dUTP:

Deoxyuridine triphosphate

EED:

Embryonic ectoderm development

ELRI:

Extremely long-range promoter-promoter interactions

EpiLC:

Epiblast-like stem cell

EpiSC:

Epiblast stem cell

Eprn:

Ephemeron

ERK/MEK:

Extracellular signal-regulated kinases/mitogen-activated protein kinase

eRNA:

Enhancer RNA

ERP27:

Endoplasmic reticulum protein 27

ESC:

Embryonic stem cell

ESRRB:

Estrogen-related receptor beta

EZH1:

Enhancer of zeste homolog 2

FGF5:

Fibroblast growth factor 5

GATAD2/3:

GATA zinc finger domain-containing protein 2/3

GBX2:

Gastrulation brain homeobox 2

GLTSCR1:

Glioma tumor suppressor candidate region gene 1

GO:

Gene ontology

GRHL2:

Grainyhead-like 2

GSK3:

Glycogen synthase kinase

HERV-H/K:

Human endogenous retrovirus-H/K

HNRNPK:

Heterogeneous nuclear ribonucleoprotein K

HIRA:

Histone cell cycle regulator

HPAT2/3/5:

Human pluripotency-associated transcripts 2/3/5

ICM:

Inner cell mass

INO80:

INO80 complex ATPase subunit

ISWI:

Chromatin remodelling complex ATPase chain Isw1

ISY1:

ISY1 splicing factor homolog

JARID2:

Jumonji and AT-rich interaction domain-containing 2

JMJD2C:

Jumonji domain 2C

KLF:

Kruppel-like factor

LEF1:

Lymphoid enhancer-binding factor 1

LincRNA:

Long intergenic ncRNAs

Lncenc1:

Long non-coding RNA, embryonic stem cells expressed 1

LncRNA:

Long non-coding RNA

MLL:

Myeloid/lymphoid leukemia

Mta:

Metastatic-associated protein

MTF2:

Metal response element-binding transcription factor 2

NANOG:

Nanog homeobox

NL:

Nuclear lamina

NURD:

Nuclear remodelling and deacetylase

OCT4:

Octamer-binding transcription factor 4

OCT6:

POU class 3 homeobox 1

OTX2:

Orthodenticle homeobox 2

PcG:

Polycomb group

PGC:

Primordial germ cell

PRC:

Polycomb repressive complex

PRDM14:

PR/SET domain 14

RbAP:

Retinoblastoma-associated-binding protein

REG2:

Regenerating islet-derived 2

REX1:

ZFP42 zinc finger protein

RRBS:

Reduced representative bisulfide sequencing

SETD1A/SETD1B:

SET domain-containing 1A/1B

SETD1B:

SET domain-containing 1B

SMARCAD1:

SWI/SNF-related, matrix-associated actin-dependent regulator of chromatin, subfamily A, containing DEAD/H box 1

SOX2:

SRY (sex-determining region Y)-box 2

STAT3:

Signal transducer and activator of transcription 3

Suz12:

Suppressor of zeste 12 protein homolog

SWI/SNF:

SWItch/sucrose non-fermentable

TAD:

Topologically associated domain

TBX2:

T-box transcription factor 2

TET:

Ten-eleven translocation

Trincr1:

TRIM71 interacting long non-coding RNA 1

TrxG:

Trithorax group

TRE:

Transregulatory element

TSS:

Transcriptional start site

ULI-NChIP:

Ultra-low-input micrococcal nuclease-based native ChIP

UTR:

Untranslated region

VE:

Vascular endothelium

VGLL1:

Vestigial-like family member 1

WDR5:

WD repeat-containing protein 5

ZFHX2:

Zinc finger homeobox 2

Zfp281:

Zinc finger protein 281

ZIC2:

Zinc finger protein ZIC 2

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Acknowledgements

Authors thank DD lab members for providing inputs in writing the manuscript.

Funding

The work is funded by Department of Biotechnology (DBT) (#BT/PR17597/MED/31/335/2016; #BT/HRD/NWBA/38/10/2018 and intramural fund to the institute). IB and PCV received support from DBT (#DBT/2020/RGCB/1331) and DST INSPIRE (#IF170833) respectively.

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Authors and Affiliations

  1. Regenerative Biology Program, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, 695014, Kerala, India

    Ishita Baral, Pallavi Chinnu Varghese & Debasree Dutta

  2. Manipal Academy of Higher Education, Karnataka State, Manipal, 576104, India

    Ishita Baral & Pallavi Chinnu Varghese

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  1. Ishita Baral
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  2. Pallavi Chinnu Varghese
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  3. Debasree Dutta
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Contributions

IB performed literature search and wrote the manuscript. PCV and AM prepared the figures. DD conceptualized the contents, prepared the final version of the manuscript, and with permission from other authors submitted to the journal.

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Correspondence to Debasree Dutta.

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Baral, I., Varghese, P.C. & Dutta, D. Epigenetics as “conductor” in “orchestra” of pluripotent states. Cell Tissue Res 390, 141–172 (2022). https://doi.org/10.1007/s00441-022-03667-0

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  • DOI: https://doi.org/10.1007/s00441-022-03667-0

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