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Cellular diversity of the regenerating caudal fin.

ABSTRACT: Zebrafish faithfully regenerate their caudal fin after amputation. During this process, both differentiated cells and resident progenitors migrate to the wound site and undergo lineage-restricted, programmed cellular state transitions to populate the new regenerate. Until now, systematic characterizations of cells comprising the new regenerate and molecular definitions of their state transitions have been lacking. We hereby characterize the dynamics of gene regulatory programs during fin regeneration by creating single-cell transcriptome maps of both preinjury and regenerating fin tissues at 1/2/4 days post-amputation. We consistently identified epithelial, mesenchymal, and hematopoietic populations across all stages. We found common and cell type-specific cell cycle programs associated with proliferation. In addition to defining the processes of epithelial replenishment and mesenchymal differentiation, we also identified molecular signatures that could better distinguish epithelial and mesenchymal subpopulations in fish. The insights for natural cell state transitions during regeneration point to new directions for studying this regeneration model.

SUBMITTER: Hou Y

PROVIDER: S-EPMC7423392 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Cellular diversity of the regenerating caudal fin.

Hou Yiran Y Lee Hyung Joo HJ Chen Yujie Y Ge Jiaxin J Osman Fujr Osman Ibrahim FOI McAdow Anthony R AR Mokalled Mayssa H MH Johnson Stephen L SL Zhao Guoyan G Wang Ting T

Science advances 20200812 33

Zebrafish faithfully regenerate their caudal fin after amputation. During this process, both differentiated cells and resident progenitors migrate to the wound site and undergo lineage-restricted, programmed cellular state transitions to populate the new regenerate. Until now, systematic characterizations of cells comprising the new regenerate and molecular definitions of their state transitions have been lacking. We hereby characterize the dynamics of gene regulatory programs during fin regener ...[more]

PMID: 32851162

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Project description:Adult zebrafish can completely regenerate their caudal fin following amputation. This complex process is initiated by the formation of an epithelial would cap over the amputation site by 12 hours post amputation (hpa). Once the cap is formed, mesenchymal cells proliferate and migrate from sites distal to the wound plane and accumulate under the epithelial cap forming the blastemal structure within 48 hpa. Blastemal cells proliferate and differentiate, replacing the amputated tissues, which are populated with angiogenic vessels and innervating nerves during the regenerative outgrowth phase which is completed around 14 days post amputation (dpa). Regenerative outgrowth does not occur in TCDD-exposed zebrafish. To identify the molecular pathways that are perturbed by TCDD exposure, male zebrafish were i.p. injected with 50 ng/g TCDD or vehicle and caudal fins were amputated. Regenerating fin tissue was collected at 1, 3 and 5 dpa for mRNA abundance analysis. Microarray analysis and quantitative real time PCR revealed that wound healing and regeneration alone altered the expression of nearly 900 genes by at least two fold between 1 and 5 dpa. TCDD altered the abundance of 370 genes at least two fold. Among these, several known aryl hydrocarbon responsive genes were identified in addition to several genes involved in extracellular matrix composition and metabolism. The profile of misexpressed genes is suggestive of impaired cellular differentiation and extracellular matrix composition potentially regulated by Sox9b. Experiment Overall Design: Regenerating fins were isolated at 1, 3 and 5 days post amputation. Three replicates were collected at each time point. 10 fins were pooled to comprise one replicate. Fish were dosed at 0 days post amputation with vehicle control alone or 50 ng/g TCDD. Experiment Overall Design: 1 Day Post Amputation Vehicle Exposed: GSM85187, GSM85188, and GSM85189 Experiment Overall Design: 1 Day Post Amputation TCDD Exposed: GSM85190, GSM85191, and GSM85192 Experiment Overall Design: 3 Days Post Amputation Vehicle Exposed: GSM85193, GSM85194, and GSM85195 Experiment Overall Design: 3 Day Post Amputation TCDD Exposed: GSM85196, GSM85197, and GSM85198 Experiment Overall Design: 5 Days Post Amputation Vehicle Exposed: GSM85199, GSM85200, and GSM85201 Experiment Overall Design: 5 Days Post Amputation TCDD Exposed: GSM85202, GSM85203, and GSM85204

Dataset Information

Cellular diversity of the regenerating caudal fin.

Publications

Cellular diversity of the regenerating caudal fin.

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