Cellular Heterogeneity and Lineage Restriction during Mouse Digit Tip Regeneration at Single-Cell Resolution

Johnson, Gemma; Masias, Erick J.; Lehoczky, Jessica A.

doi:10.1016/j.devcel.2020.01.026

Cited by 61 publications

(98 citation statements)

References 70 publications

(134 reference statements)

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“…500 μl 2% SDS in 50 mM ammonium bicarbonate in MS-grade water was added to the bead pellet, and the mixture was transferred into a low-protein-binding tube. Beads were then washed ( Goldman et al, 2017 ) twice with 500 μl 0.5% SDS in 50 mM ammonium bicarbonate ( Hoang et al, 2020 ), twice with 1% Triton X-100/1% deoxycholate/25 mM LiCl in 50 mM ammonium bicarbonate ( Johnson et al, 2020 ), twice with 0.5 M NaCl in 50 mM ammonium bicarbonate, and two times with 50 mM ammonium bicarbonate solution. For each wash step, 500 μl wash solution was used and samples were rocked for 10 min at RT.…”

Section: Methodsmentioning

confidence: 99%

“…Understanding how and why tissue regeneration occurs is a central objective of developmental biology. Genome-wide transcriptome or chromatin profiling experiments using RNA-seq, scRNA-seq, ATAC-seq, or ChIP-seq approaches have helped to identify novel factors, mechanisms, and concepts that have informed our understanding of regeneration in many tissues, injury contexts, and species ( Goldman et al, 2017 ; Hoang et al, 2020 ; Johnson et al, 2020 ). Although key for detecting and inferring changes in gene transcription, chromatin organization, or DNA–protein associations, these strategies are limited in their abilities to identify protein and signaling complexes that carry out changes at the cell and tissue level.…”

Section: Introductionmentioning

confidence: 99%

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In vivo proximity labeling identifies cardiomyocyte protein networks during zebrafish heart regeneration

Pronobis

Zheng

Singh

et al. 2021

eLife

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Strategies have not been available until recently to uncover interacting protein networks specific to key cell types, their subcellular compartments, and their major regulators during complex in vivo events. Here we apply BioID2 proximity labeling to capture protein networks acting within cardiomyocytes during a key model of innate heart regeneration in zebrafish. Transgenic zebrafish expressing a promiscuous BirA2 localized to the entire myocardial cell or membrane compartment were generated, each identifying distinct proteomes in adult cardiomyocytes that became altered during regeneration. BioID2 profiling for interactors with ErbB2, a co-receptor for the cardiomyocyte mitogen Nrg1, implicated Rho A as a target of ErbB2 signaling in cardiomyocytes. Blockade of Rho A during heart regeneration, or during cardiogenic stimulation by the mitogenic influences Nrg1, Vegfaa or Vitamin D, disrupted muscle creation. Our findings reveal proximity labeling as a useful resource to interrogate cell proteomes and signaling networks during tissue regeneration in zebrafish.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In vivo proximity labeling identifies cardiomyocyte protein networks during zebrafish heart regeneration

Pronobis

Zheng

Singh

et al. 2021

eLife

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“…The gene aspr encodes a secreted protein with multiple EGF-repeats important for regeneration (Harris et al ., 2020). Pvf1 binds to its receptor Pvr and the resulting signaling is known to contribute to wound healing (Wu et al ., 2009), and homologs are involved in regeneration in other systems (Currie et al ., 2016; Johnson et al ., 2020). We determined that Pvf1, upd3 , and Ilp8 were all expressed at the center of the blastema (Figure 1H, I; supplemental fig.…”

Section: Figurementioning

confidence: 99%

Critical genetic program forDrosophilaimaginal disc regeneration revealed by single-cell analysis

Worley

Everetts

Yasutomi

et al. 2021

Preprint

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Whether regeneration is primarily accomplished by re-activating gene regulatory networks used previously during development or by activating novel regeneration-specific transcriptional programs remains a longstanding question. Currently, most genes implicated in regeneration also function during development. Using single-cell transcriptomics in regenerating Drosophila wing discs, we identified two regeneration-specific cell populations within the blastema. They are each composed of cells that upregulate multiple genes encoding secreted proteins that promote regeneration. In this regenerative secretory zone, the transcription factor Ets21C controls the expression of multiple regenerationpromoting genes. While eliminating Ets21C function has no discernible effect on development, it severely compromises regeneration. This Ets21C-dependent gene regulatory network is also activated in blastema-like cells in tumorous discs, suggesting that pro-regenerative mechanisms can be co-opted by tumors to promote aberrant growth.

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“…The same transplantation, performed in the proximally amputated, therefore non-regenerative digits, had no similar effect on the phenotype of the introduced cells, confirming the role of blastema in altering the inherent cells’ transcriptional state [ 50 ]. Cell population in the early blastema (11–17 days post-amputation) of the regenerating digit tip was recently analyzed via scRNA-seq by Johnson et al [ 64 ], who identified the very same broad cell types in the intact unamputated digit tip. The most abundant and heterogeneous population within the blastema were fibroblasts, which were also observed to be enriched in several regeneration-specific markers, including a novel Mest gene [ 64 ].…”

Section: Digit Regenerationmentioning

confidence: 99%

“…Cell population in the early blastema (11–17 days post-amputation) of the regenerating digit tip was recently analyzed via scRNA-seq by Johnson et al [ 64 ], who identified the very same broad cell types in the intact unamputated digit tip. The most abundant and heterogeneous population within the blastema were fibroblasts, which were also observed to be enriched in several regeneration-specific markers, including a novel Mest gene [ 64 ]. The Mest gene expression was previously identified in mesenchymal tissues of the developing embryo [ 65 ].…”

Section: Digit Regenerationmentioning

confidence: 99%

The Potential of Nail Mini-Organ Stem Cells in Skin, Nail and Digit Tips Regeneration

Pulawska-Czub

Pieczonka

Mazurek

et al. 2021

IJMS

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Nails are highly keratinized skin appendages that exhibit continuous growth under physiological conditions and full regeneration upon removal. These mini-organs are maintained by two autonomous populations of skin stem cells. The fast-cycling, highly proliferative stem cells of the nail matrix (nail stem cells (NSCs)) predominantly replenish the nail plate. Furthermore, the slow-cycling population of the nail proximal fold (nail proximal fold stem cells (NPFSCs)) displays bifunctional properties by contributing to the peri-nail epidermis under the normal homeostasis and the nail structure upon injury. Here, we discuss nail mini-organ stem cells’ location and their role in skin and nail homeostasis and regeneration, emphasizing their importance to orchestrate the whole digit tip regeneration. Such endogenous regeneration capabilities are observed in rodents and primates. However, they are limited to the region adjacent to the nail’s proximal area, indicating the crucial role of nail mini-organ stem cells in digit restoration. Further, we explore the molecular characteristics of nail mini-organ stem cells and the critical role of the bone morphogenetic protein (BMP) and Wnt signaling pathways in homeostatic nail growth and digit restoration. Finally, we investigate the latest accomplishments in stimulating regenerative responses in regeneration-incompetent injuries. These pioneer results might open up new opportunities to overcome amputated mammalian digits and limbs’ regenerative failures in the future.

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Cellular Heterogeneity and Lineage Restriction during Mouse Digit Tip Regeneration at Single-Cell Resolution

Cited by 61 publications

References 70 publications

In vivo proximity labeling identifies cardiomyocyte protein networks during zebrafish heart regeneration

In vivo proximity labeling identifies cardiomyocyte protein networks during zebrafish heart regeneration

Critical genetic program forDrosophilaimaginal disc regeneration revealed by single-cell analysis

The Potential of Nail Mini-Organ Stem Cells in Skin, Nail and Digit Tips Regeneration

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