Delineating chromatin accessibility re-patterning at single cell level during early stage of direct cardiac reprogramming

Wang, Haofei; Yang, Yuchen; Qian, Yunzhe; Liu, Jiandong; Li, Qian

doi:10.1016/j.yjmcc.2021.09.002

Cited by 23 publications

(17 citation statements)

References 26 publications

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“…We also noted the involvement of several AP-1 factors, both from our network analyses and in silico simulations, including Fos , Fosb , Fosl2 , and Junb . The FOS-JUN-AP1 complex has been reported to regulate reprogramming to pluripotency ( Xing et al., 2020 ) and direct reprogramming to cardiomyocytes ( Wang et al., 2022a ); thus, we selected Fos for further investigation.…”

Section: Discussionmentioning

confidence: 99%

Gene regulatory network reconfiguration in direct lineage reprogramming

Kamimoto¹,

Adil²,

Jindal³

et al. 2023

Stem Cell Reports

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Section: Discussionmentioning

confidence: 99%

Gene regulatory network reconfiguration in direct lineage reprogramming

Kamimoto¹,

Adil²,

Jindal³

et al. 2023

Stem Cell Reports

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“…We also noted the involvement of several AP-1 factors, both from our network analyses and in silico simulations, including Fos, Fosb, Fosl2, and Junb . The FOS-JUN-AP1 complex has been reported to regulate reprogramming to pluripotency (Xing et al, 2020) and direct reprogramming to cardiomyocytes (Wang et al, 2022); thus, we selected Fos for further investigation.…”

Section: Discussionmentioning

confidence: 99%

Gene Regulatory Network Reconfiguration in Direct Lineage Reprogramming

Kamimoto

Adil

Jindal

et al. 2022

Preprint

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In direct lineage reprogramming, transcription factor (TF) overexpression reconfigures Gene Regulatory Networks (GRNs) to convert cell identities between fully differentiated cell types. We previously developed CellOracle, a computational pipeline that integrates single-cell transcriptome and epigenome profiles to infer GRNs. CellOracle leverages these inferred GRNs to simulate gene expression changes in response to TF perturbation, enabling network re-configuration during reprogramming to be interrogated in silico. Here, we integrate CellOracle analysis with lineage tracing of fibroblast to induced endoderm progenitor (iEP) conversion, a prototypical direct lineage reprogramming paradigm. By linking early network state to reprogramming success or failure, we reveal distinct network configurations underlying different reprogramming outcomes. Using these network analyses and in silico simulation of TF perturbation, we identify new factors to coax cells into successfully converting cell identity, uncovering a central role for the AP-1 subunit Fos with the Hippo signaling effector, Yap1. Together, these results demonstrate the efficacy of CellOracle to infer and interpret cell-type-specific GRN configurations at high resolution, providing new mechanistic insights into the regulation and reprogramming of cell identity.

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“…Thus, both cell types make attractive starting cell populations for neuronal reprogramming in vivo. molecular insights into cell trajectories during direct reprogramming in cell culture (Cates et al, 2021;Horisawa et al, 2020;Karow et al, 2018;Kempf et al, 2021;Kim et al, 2021;Stone et al, 2019;Treutlein et al, 2016;Wang et al, 2021b;Zhou et al, 2019).…”

Section: Reprogramming Trajectoriesmentioning

confidence: 99%

“…Various co-factors that assist the erasure of epigenetic barriers to reprogramming (e.g. repressive DNA methylation and histone modifications) can improve transcription factor-mediated reprogramming (Elhanani et al, 2020;Garry et al, 2021;Jorstad et al, 2017;VandenBosch et al, 2020;Wang et al, 2021b). Now, increasing attention is turning towards exploiting pathways through which microRNAs post-transcriptionally regulate cell identity for lineage reprogramming (Cates et al, 2021;Jayawardena et al, 2015;Wang et al, 2021d;Yang et al, 2021).…”

Section: Reprogramming Trajectoriesmentioning

confidence: 99%

Reprogramming cellular identity in vivo

2022

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Cellular identity is established through complex layers of genetic regulation, forged over a developmental lifetime. An expanding molecular toolbox is allowing us to manipulate these gene regulatory networks in specific cell types in vivo. In principle, if we found the right molecular tricks, we could rewrite cell identity and harness the rich repertoire of possible cellular functions and attributes. Recent work suggests that this rewriting of cell identity is not only possible, but that newly induced cells can mitigate disease phenotypes in animal models of major human diseases. So, is the sky the limit, or do we need to keep our feet on the ground? This Spotlight synthesises key concepts emerging from recent efforts to reprogramme cellular identity in vivo. We provide our perspectives on recent controversies in the field of glia-to-neuron reprogramming and identify important gaps in our understanding that present barriers to progress.

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Delineating chromatin accessibility re-patterning at single cell level during early stage of direct cardiac reprogramming

Cited by 23 publications

References 26 publications

Gene regulatory network reconfiguration in direct lineage reprogramming

Gene regulatory network reconfiguration in direct lineage reprogramming

Gene Regulatory Network Reconfiguration in Direct Lineage Reprogramming

Reprogramming cellular identity in vivo

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