CBP/p300 homologs CBP2 and CBP3 play distinct roles in planarian stem cell function

Stelman, Clara R.; Smith, Britessia M.; Chandra, Bidushi; Roberts-Galbraith, Rachel H.

doi:10.1016/j.ydbio.2021.02.004

Cited by 15 publications

(18 citation statements)

References 118 publications

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“…Because acetyl-CoA can also enter the citric acid cycle to produce alpha-ketoglutarate, a substrate for histone demethylation 71 , ApoB inhibition could dysregulate epigenetic changes through multiple pathways. Histone acetylases, deacetylases, methyltransferases, and demethylases are conserved in planarians, and their inhibition disrupts stem cell maintenance, differentiation, and regeneration 64, 65, 72–75 . Because apob RNAi results in widespread dysregulation of thousands of transcripts associated with differentiating progeny, it is reasonable to suggest that in planarians, intestinal lipid stores serve as a ready carbon source that is trafficked by ApoB-containing LPs to neoblasts and progeny to support epigenetic modifications required for differentiation.…”

Section: Discussionmentioning

confidence: 99%

Intestine-enrichedapolipoprotein borthologs are required for stem cell differentiation and regeneration in planarians

Wong

Cejda

et al. 2021

Preprint

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Little is known about how lipid mobilization and utilization are modulated during stem-cell-driven tissue growth during regeneration. Planarian flatworms can regenerate all missing tissues in 10 days due to the proliferation and differentiation of pluripotent somatic stem cells called neoblasts. In planarians, diet-derived neutral lipids are stored in the intestine. Here, we identify two intestine-enriched paralogs of apolipoprotein b, apob-1 and apob-2, that are required for regeneration. Consistent with apolipoproteins' known roles regulating neutral lipid (NL) transport in lipoprotein particles (LPs), NLs increased in the intestine upon simultaneous dsRNA-mediated knockdown of apob-1 and apob-2, but were depleted in neoblasts and their progeny. apob knockdown reduced regeneration blastema morphogenesis, and delayed re-establishment of axial polarity and regeneration of multiple organs. Using flow cytometry, we found that neoblast progeny accumulated in apob(RNAi) animals, with minimal effects on neoblast maintenance or proliferation. In addition, ApoB reduction primarily dysregulated expression of transcripts enriched in neoblast progeny and mature cell types, compared to cycling neoblasts. Together, our results provide evidence that intestine-derived lipids serve as a source of metabolites required for neoblast differentiation. In addition, these findings demonstrate that planarians are a tractable model for elucidating specialized mechanisms by which lipid metabolism must be regulated during animal regeneration.

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Section: Discussionmentioning

confidence: 99%

Intestine-enrichedapolipoprotein borthologs are required for stem cell differentiation and regeneration in planarians

Wong

Cejda

et al. 2021

Preprint

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“…In recent years significant progress has been made in order to understand the role of PTMs and epigenetic modifications on planarian regeneration [119,126]. Strand and collaborators have reviewed extensively how post-translational modifications regulate planarian regeneration, mainly phosphorylation, ubiquitination and chromatin modifications [118].…”

Section: Post-translational Modifications and Epigenetic Regulation In Neoblastsmentioning

confidence: 99%

“…Recently, two different studies have uncovered the function of the planarian CREBbinding protein (CBP)/p300 family in neoblast biology [126,140]. These transcriptional co-activators play different roles either by acetylating both histone and non-histone proteins (i.e., transcription factors) or serving as protein scaffolds [141][142][143].…”

Section: Post-translational Modifications and Epigenetic Regulation In Neoblastsmentioning

confidence: 99%

Decoding Stem Cells: An Overview on Planarian Stem Cell Heterogeneity and Lineage Progression

Molina

Cebrià

2021

Biomolecules

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Planarians are flatworms capable of whole-body regeneration, able to regrow any missing body part after injury or amputation. The extraordinary regenerative capacity of planarians is based upon the presence in the adult of a large population of somatic pluripotent stem cells. These cells, called neoblasts, offer a unique system to study the process of stem cell specification and differentiation in vivo. In recent years, FACS-based isolation of neoblasts, RNAi functional analyses as well as high-throughput approaches such as single-cell sequencing have allowed a rapid progress in our understanding of many different aspects of neoblast biology. Here, we summarize our current knowledge on the molecular signatures that define planarian neoblasts heterogeneity, which includes a percentage of truly pluripotent stem cells, and guide the commitment of pluripotent neoblasts into lineage-specific progenitor cells, as well as their differentiation into specific planarian cell types.

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“…In addition, the CREB-binding protein (CBP) and p300 family of histone acetyltransferases homologs Smed-CBP2 and Smed-CBP3 displayed distinct roles in stem cell maintenance and functions 17 .…”

Section: Introductionmentioning

confidence: 99%

“…Mihaylova et al found that the COMPASS family MLL3/4 histone methyltransferases are essential for the differentiation and regeneration of the planarian 16 . In addition, the CREB-binding protein (CBP) and p300 family of histone acetyltransferases homologs Smed -CBP2 and Smed -CBP3 displayed distinct roles in stem cell maintenance and functions 17 .…”

Section: Introductionmentioning

confidence: 99%

m⁶A-mediated Cell-cell Communication Controls Planarian Regeneration

Cui

Zhou

et al. 2021

Preprint

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Regeneration is the regrowth of damaged tissues or organs, a vital mechanism responding to damages from primitive organisms to higher mammals. Planarian possesses active whole-body regenerative capability owning to its vast reservoir of adult stem cells, neoblasts, thus provides an ideal model to delineate the underlying mechanisms for regeneration. N6-methyladenosine (m6A) regulates stem cell renewal and differentiation. However, how m6A controls regeneration at whole-organism level remains largely unknown. Here, we demonstrate that the depletion of m6A methyltransferase regulatory subunit wtap abolishes planarian regeneration, through regulating cell-cell communication and cell cycle. scRNA-Seq analysis unveils that the wtap knockdown induces a unique type of neural progenitor-like cells (NP-like cells), characterized by specific expression of the cell-cell communication ligand grn. Intriguingly, the depletion of m6A-modified transcripts grn/cdk9 (or cdk7) axis rescues the defective regeneration of planarian without wtap. Overall, our study reveals an indispensable role of m6A-dependent cell-cell communication essential for whole-organism regeneration.

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CBP/p300 homologs CBP2 and CBP3 play distinct roles in planarian stem cell function

Cited by 15 publications

References 118 publications

Intestine-enrichedapolipoprotein borthologs are required for stem cell differentiation and regeneration in planarians

Intestine-enrichedapolipoprotein borthologs are required for stem cell differentiation and regeneration in planarians

Decoding Stem Cells: An Overview on Planarian Stem Cell Heterogeneity and Lineage Progression

m⁶A-mediated Cell-cell Communication Controls Planarian Regeneration

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CBP/p300 homologs CBP2 and CBP3 play distinct roles in planarian stem cell function

Cited by 15 publications

References 118 publications

Intestine-enrichedapolipoprotein borthologs are required for stem cell differentiation and regeneration in planarians

Intestine-enrichedapolipoprotein borthologs are required for stem cell differentiation and regeneration in planarians

Decoding Stem Cells: An Overview on Planarian Stem Cell Heterogeneity and Lineage Progression

m6A-mediated Cell-cell Communication Controls Planarian Regeneration

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Product

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m⁶A-mediated Cell-cell Communication Controls Planarian Regeneration