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Single-cell division tracing and transcriptomics reveal cell types and differentiation paths in the regenerating lung
This study uses single-cell transcriptomics to examine how lung cells respond to targeted damage. The authors employ genetically modified mouse models and cell sorting to enrich for rare, actively dividing cells, revealing cell types/states and alternative differentiation paths.
- Leila R. Martins
- , Lina Sieverling
- & Claudia Scholl
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Drosophila activins adapt gut size to food intake and promote regenerative growth
While activins are critical regulators of early development, their role in maintaining adult tissue homeostasis remains obscure. Here the authors explore the role of activins in promoting intestinal regeneration and nutrient-dependent gut resizing in Drosophila.
- Christian F. Christensen
- , Quentin Laurichesse
- & Ditte S. Andersen
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Common and divergent gene regulatory networks control injury-induced and developmental neurogenesis in zebrafish retina
The molecular mechanisms controlling injury-dependent neuronal regeneration are largely unknown. Here, the authors use integrated multiomic analysis to characterize gene regulatory networks controlling injury-induced neurogenesis in zebrafish retina
- Pin Lyu
- , Maria Iribarne
- & Seth Blackshaw
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Reassessing endothelial-to-mesenchymal transition in mouse bone marrow: insights from lineage tracing models
Endothelial cells (ECs) and bone marrow stromal cells (BMSCs) support hematopoiesis and hematopoietic regeneration. Whether ECs are a source of BMSCs remains unclear. Here, using lineage tracing models the authors show that ECs are not a source of BMSCs during homeostasis and regeneration.
- Jia Cao
- , Ling Jin
- & Hui Xie
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Apoptotic dysregulation mediates stem cell competition and tissue regeneration
The authors show that depletion of pro-apoptotic Bax protein bestows hair follicle stem cells with the capacity to eliminate viable neighboring cells by sequestration of TNFα, resulting in an increased stem cell pool, accelerated wound repair and de novo hair follicle regeneration.
- Marianna Yusupova
- , Roi Ankawa
- & Yaron Fuchs
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Fate specification is spatially intermingled across planarian stem cells
Stem cells can select among a wide array of fates. Here, the authors utilize spatial transcriptomics and three-dimensional neighborhood analysis to uncover that fate choices in planarian stem cells occur in a highly intermingled pattern.
- Chanyoung Park
- , Kwadwo E. Owusu-Boaitey
- & Peter W. Reddien
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Proenkephalin-A secreted by renal proximal tubules functions as a brake in kidney regeneration
The coordination of pro- and anti-regenerative factors is essential for organ regeneration. The authors show here that proenkephalin-A, secreted by proximal renal tubules in zebrafish, negatively regulates hydrogen peroxide production remodelling H3K4me3 in renal progenitor cells and controlling kidney regeneration strength.
- Chi Liu
- , Xiaoliang Liu
- & Jinghong Zhao
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Gli1 marks a sentinel muscle stem cell population for muscle regeneration
Adult skeletal muscle regeneration is mainly driven by muscle stem cells (MuSCs), which are highly heterogeneous. Here, the authors found that a population of MuSCs, marked by Gli1 expression, is key contributor to muscle regeneration.
- Jiayin Peng
- , Lili Han
- & Yun Zhao
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Organoids transplantation attenuates intestinal ischemia/reperfusion injury in mice through L-Malic acid-mediated M2 macrophage polarization
Intestinal ischemia/reperfusion (I/R) injury is a life-threatening problem in surgeries. Here, authors report that intestinal organoids transplantation attenuates intestinal I/R injury in mice through L-Malic acid-mediated M2 macrophage polarization.
- Fang-Ling Zhang
- , Zhen Hu
- & Ke-Xuan Liu
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Multi-species atlas resolves an axolotl limb development and regeneration paradox
Single-cell transcriptomic cross-species comparison identifies critical limb developmental cell type apical-ectodermal ridge in the prime limb regeneration model axolotl, and its differential usage during amphibian limb regeneration.
- Jixing Zhong
- , Rita Aires
- & Can Aztekin
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Mechanically induced pyroptosis enhances cardiosphere oxidative stress resistance and metabolism for myocardial infarction therapy
Therapeutic options for myocardial infarction therapy remain limited. Here the authors report the application of an optimized liquid crystal substrate in the mass production and effective preconditioning of cardiospheres, which could generate cardiospheres with improved cell bioactivity and resistance to oxidative stress for myocardial infarction therapy.
- Yingwei Wang
- , Qi Li
- & Zheng Wu
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Perivascular niche cells sense thrombocytopenia and activate hematopoietic stem cells in an IL-1 dependent manner
Hematopoietic stem cells (HSCs) replenish blood cells. Here, Luis et al., identify a feedback mechanism by which IL-1 secreted by activated platelets signals through niche Lepr+ cells to activate HSCs and restore platelet homeostasis.
- Tiago C. Luis
- , Nikolaos Barkas
- & Sten Eirik W. Jacobsen
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ATF3 induction prevents precocious activation of skeletal muscle stem cell by regulating H2B expression
Muscle regeneration relies on activation and expansion of skeletal muscle stem cells. Here, authors show that ATF3 induction prevents precocious activation of skeletal muscle stem cells by binding and promoting the transcription of Histone2B.
- Suyang Zhang
- , Feng Yang
- & Huating Wang
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Spinal cord repair is modulated by the neurogenic factor Hb-egf under direction of a regeneration-associated enhancer
Zebrafish can regenerate after paralyzing spine injuries and regain locomotor ability, unlike mammals. Here authors show that the neurogenic factor Hb-egf promotes spinal cord regeneration in zebrafish and is regulated by an enhancer that can similarly direct expression in the pro-regenerative setting of neonatal mice.
- Valentina Cigliola
- , Adam Shoffner
- & Kenneth D. Poss
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Hdac1 and Hdac2 regulate the quiescent state and survival of hair-follicle mesenchymal niche
Cell division and stem cell maintenance are tightly linked. Here they show that in the hair follicle an epigenetic mechanism maintains mesenchymal niche dormancy in a highly proliferative microenvironment while repurposing mitogenic signaling to orchestrate the hair cycle clock.
- Hadas Sibony-Benyamini
- , Emil Aamar
- & David Enshell-Seijffers
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Single-cell analysis of lizard blastema fibroblasts reveals phagocyte-dependent activation of Hedgehog-responsive chondrogenesis
Lizards are the closest known relatives of mammals capable of epimorphic tail regrowth. Here, single-cell analysis of regenerating lizard tails reveals a phagocyte-induced fibroblast population contributing to blastema formation and chondrogenesis.
- Ariel C. Vonk
- , Xiaofan Zhao
- & Thomas P. Lozito
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Hedgehog signaling via its ligand DHH acts as cell fate determinant during skeletal muscle regeneration
Successful skeletal muscle regeneration relies on the interplay of multiple cell populations. Here, the authors describe how ciliary Hedgehog signaling coordinates the intercellular crosstalk required to balance wound healing and fatty fibrosis.
- Alessandra M. Norris
- , Ambili Bai Appu
- & Daniel Kopinke
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Spatiotemporal transcriptomic atlas reveals the dynamic characteristics and key regulators of planarian regeneration
Cui et al. present a comprehensive three-dimensional spatiotemporal transcriptome landscape of planarian regeneration. They identified a novel pluripotent neoblast subtype and new spatially specific genes essential to tissue regeneration.
- Guanshen Cui
- , Kangning Dong
- & Yun-Gui Yang
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Acoel single-cell atlas reveals expression dynamics and heterogeneity of adult pluripotent stem cells
Multiple species can achieve whole-body regeneration through the action of adult stem cells, though little is known about how these cells compare across species. Here they investigated the stem cells of a marine worm, the acoel Hofstenia miamia, and identified heterogeneity of these cells during development and regeneration.
- Ryan E. Hulett
- , Julian O. Kimura
- & Mansi Srivastava
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Methionine adenosyltransferase2A inhibition restores metabolism to improve regenerative capacity and strength of aged skeletal muscle
Aged myoblasts suffer from impaired glycolysis and insulin resistance, but increase methionine catabolism, possibly to meet energetic demands. Here, authors show that inhibiting methionine metabolism via NANOG reprogramming or MAT2A inhibition restores the function and regeneration capacity of aged muscle.
- Nika Rajabian
- , Izuagie Ikhapoh
- & Stelios T. Andreadis
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Wnt/β-catenin signalling is required for pole-specific chromatin remodeling during planarian regeneration
Any planarian fragment regenerates the missing head and tail in the proper end. Early activation of the Wnt/β-catenin signaling pathway changes the chromatin accessibility of the cells of the posterior-facing wound to regenerate a tail.
- Eudald Pascual-Carreras
- , Marta Marín-Barba
- & Teresa Adell
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Senescent cells perturb intestinal stem cell differentiation through Ptk7 induced noncanonical Wnt and YAP signaling
Cellular senescence and associated secretory phenotype (SASP) are thought to contribute to aging and tissue dysfunction, though it is unclear how SASP impacts regeneration. Here the authors show that SASP factors impair regeneration, and that Ptk7 is a key secreted protein mediating that dysregulation.
- Jina Yun
- , Simon Hansen
- & Heinrich Jasper
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Adipose tissue is a source of regenerative cells that augment the repair of skeletal muscle after injury
The dynamics of fibroadipogenic progenitors (FAPs) after muscle injury are crucial to ensure efficient regeneration. Here the authors show that a pool of FAPs originates from adipose tissue and are necessary for effective muscle regeneration.
- Quentin Sastourné-Arrey
- , Maxime Mathieu
- & Coralie Sengenès
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Activation of a transient progenitor state in the epicardium is required for zebrafish heart regeneration
The epicardium supports heart regeneration, though precisely how is unclear. Here the authors define an activated epicardial progenitor population as the source of essential cell types and paracrine factors for successful heart regeneration in zebrafish.
- Yu Xia
- , Sierra Duca
- & Jingli Cao
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Bead-jet printing enabled sparse mesenchymal stem cell patterning augments skeletal muscle and hair follicle regeneration
Current mesenchymal stem cell (MSC) transplantation practices are limited by the loss or reduced performance of MSCs. Here the authors develop a bead-jet printer for intraoperative formulation and printing of MSCs-laden Matrigel beads to improve skeletal muscle and hair follicle regeneration.
- Yuanxiong Cao
- , Jiayi Tan
- & Shaohua Ma
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IL6 supports long-term expansion of hepatocytes in vitro
Hepatocytes are very difficult to expand in vitro. Here the authors discover that IL6 promotes long-term expansion (>30 passages) of primary mouse hepatocytes in vitro by converting the cells into hepatic progenitor cells, which maintain full capacity of differentiation into hepatocytes.
- Ren Guo
- , Mengmeng Jiang
- & Xin Xie
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Enhanced metanephric specification to functional proximal tubule enables toxicity screening and infectious disease modelling in kidney organoids
Proximal nephron in pluripotent stem cell derived kidney organoids are immature with limited support for functional solute channels. Vanslambrouck et al report improved metanephric specification, generating enhanced kidney organoids with superior proximal tubules, spatially arranged nephrons, and applications for disease research, and drug screening.
- Jessica M. Vanslambrouck
- , Sean B. Wilson
- & Melissa H. Little
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Msx1+ stem cells recruited by bioactive tissue engineering graft for bone regeneration
Critical-sized bone defects still present clinical challenges. Here the authors show that transplantation of neurotrophic supplement-incorporated hydrogel grafts promote full-thickness regeneration of the calvarium and perform scRNA-seq to reveal contributing stem/progenitor cells, notably a resident Msx1+ skeletal stem cell population.
- Xianzhu Zhang
- , Wei Jiang
- & Hongwei Ouyang
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Cellular taxonomy of Hic1+ mesenchymal progenitor derivatives in the limb: from embryo to adult
Mesenchymal progenitors (MPs) are fundamental to tissue development and regeneration, however, their embryonic origin is unclear. Single cell-omics coupled with lineage tracing reveal a unique somite-derived MP hierarchy in limb morphogenesis.
- Martin Arostegui
- , R. Wilder Scott
- & T. Michael Underhill
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Multiscale light-sheet organoid imaging framework
Live imaging of organoid growth remains a challenge: it requires long-term imaging of several samples simultaneously and dedicated analysis pipelines. Here the authors report an experimental and image processing framework to turn long-term light-sheet imaging of intestinal organoids into digital organoids.
- Gustavo de Medeiros
- , Raphael Ortiz
- & Prisca Liberali
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Thy1 marks a distinct population of slow-cycling stem cells in the mouse epidermis
Koren and Feldman et al. report a distinct population of Thy1-expressing stem cells in the basal layer of the mouse epidermis. These stem cells do not compete neutrally and contribute long-term to both epidermal replenishment and wound repair.
- Elle Koren
- , Alona Feldman
- & Yaron Fuchs
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GLI3 regulates muscle stem cell entry into GAlert and self-renewal
Primary cilia regulate the processing of the GLI transcription factors and Hedgehog signaling. Here, the authors show that cilia-related GLI3 controls both the quiescence-to-activation transition and self-renewal in muscle stem cells.
- Caroline E. Brun
- , Marie-Claude Sincennes
- & Michael A. Rudnicki
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Intestine-enriched apolipoprotein b orthologs are required for stem cell progeny differentiation and regeneration in planarians
Lipid metabolism regulates stem cell states and differentiation. Here, the authors demonstrate a requirement in planarians for Apolipoprotein B-mediated neutral lipid transport from intestinal stores to stem cells and their progeny during differentiation and whole-body regeneration.
- Lily L. Wong
- , Christina G. Bruxvoort
- & David J. Forsthoefel
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Article
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Activation of Nkx2.5 transcriptional program is required for adult myocardial repair
Cardiac developmental genes have been associated with regenerative potential. Here the authors identify a Nkx2.5-dependent gene regulatory network operating through ect2, psmb3, and psmd7 to orchestrate cell cycle re-entry, proteolysis, and mitochondrial metabolism during myocardial repair.
- Carmen de Sena-Tomás
- , Angelika G. Aleman
- & Kimara L. Targoff
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The planarian wound epidermis gene equinox is required for blastema formation in regeneration
Many regenerative animals form an outgrowth at wound sites called a blastema. Here the authors identify equinox, which is expressed in the planarian wound epidermis and essential to initiate positional information regeneration and blastema formation.
- M. Lucila Scimone
- , Jennifer K. Cloutier
- & Peter W. Reddien
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A conserved YAP/Notch/REST network controls the neuroendocrine cell fate in the lungs
Notch signaling is known to control neuroendocrine fate in the lungs. Shue and colleagues further identify the REST and YAP transcriptional regulators as key components of the Notch signaling pathway in the control of the neuroendocrine cell fate in lung development, lung injury response, and small-cell lung cancer.
- Yan Ting Shue
- , Alexandros P. Drainas
- & Julien Sage
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An instantly fixable and self-adaptive scaffold for skull regeneration by autologous stem cell recruitment and angiogenesis
Limited stem cells and mismatched interface fusion have plagued biomaterial-mediated cranial reconstruction. Here, the authors engineer an instantly fixable and self-adaptive scaffold to promote calcium chelation and interface integration, regulate macrophage M2 polarization, and recruit endogenous stem cells.
- Gonggong Lu
- , Yang Xu
- & Xingdong Zhang
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Distinctive molecular features of regenerative stem cells in the damaged male germline
Male germline regeneration after damage is dependent on spermatogonial stem cells (SSCs) but pathways mediating the regenerative response are unclear. Here the authors define roles for growth factor signalling and mTORC1 in SSC-driven regeneration.
- Hue M. La
- , Jinyue Liao
- & Robin M. Hobbs
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A FoxA2+ long-term stem cell population is necessary for growth plate cartilage regeneration after injury
The growth plate cartilage supports long bone growth. Here the authors identify FoxA2+ long term stem cells in the growth plate that are stratified with short term PTHrP+ cells, participate in production of hyaline cartilage, expand in response to trauma, and whose ablation impairs cartilage regeneration.
- Shanmugam Muruganandan
- , Rachel Pierce
- & Andreia M. Ionescu
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Article
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Cell-intrinsic Aryl Hydrocarbon Receptor signalling is required for the resolution of injury-induced colonic stem cells
Rapid intestinal regeneration after injury is critical to maintain barrier integrity and homeostasis, but must be tightly controlled to prevent tumorigenesis. Here they show that the aryl hydrocarbon receptor is required to terminate the regenerative response after wound healing.
- Kathleen Shah
- , Muralidhara Rao Maradana
- & Brigitta Stockinger
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Article
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Spatiotemporal reprogramming of differentiated cells underlies regeneration and neoplasia in the intestinal epithelium
Rapid turnover and regeneration of intestinal epithelium requires distinct intestinal stem cell (ISC) populations. Here the authors show p57 marks quiescent ISCs, and that differentiated cells revert to stem cell state after injury, through dynamic reprogramming characterized by fetal- and metaplastic-like changes.
- Tsunaki Higa
- , Yasutaka Okita
- & Keiichi I. Nakayama
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Article
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Tig1 regulates proximo-distal identity during salamander limb regeneration
The mechanisms by which cells determine their position within the 3D space are poorly understood. Research in salamanders offers fresh insights into this question, uncovering Tig1 as a central determinant of proximo-distal identity in regeneration.
- Catarina R. Oliveira
- , Dunja Knapp
- & Maximina H. Yun
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Article
| Open Access
Breast tissue regeneration is driven by cell-matrix interactions coordinating multi-lineage stem cell differentiation through DDR1
Mammary morphogenesis is a complex process. Here the authors describe how stem cells build a three-dimensional self-organizing multi-lineage tissue by showing that positional signals from the extracellular matrix through the collagen receptor DDR1 lead stem cells to differentiate into multi-lineage committed multi-layered progeny.
- Gat Rauner
- , Dexter X. Jin
- & Charlotte Kuperwasser
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Article
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Non-canonical Wnt signaling promotes directed migration of intestinal stem cells to sites of injury
Stem cell migration is critical during adult tissue regeneration. Here, the authors demonstrate that enteroendocrine cells coordinate stem cell migration towards sites of injury in the Drosophila intestine by activating non-canonical Wnt signaling.
- Daniel Jun-Kit Hu
- , Jina Yun
- & Heinrich Jasper
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Article
| Open Access
Hox genes regulate asexual reproductive behavior and tissue segmentation in adult animals
Hox genes are highly conserved and well-known for their role in segmental patterning during early development. Here, the authors identify an unreported role for Hox genes in the adult tissue patterning and fission behavior required for asexual reproduction in planarian flatworms.
- Christopher P. Arnold
- , Analí Migueles Lozano
- & Alejandro Sánchez Alvarado
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Article
| Open Access
Smooth muscle-specific MMP17 (MT4-MMP) regulates the intestinal stem cell niche and regeneration after damage
While the role of smooth muscle in peristalsis has been studied extensively, little is known about its other functions in the intestine. Here the authors identify MMP17, expressed by smooth muscle cells, as a modulator of intestinal epithelial regeneration and the intestinal stem cell niche.
- Mara Martín-Alonso
- , Sharif Iqbal
- & Menno J. Oudhoff
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Article
| Open Access
NRG1/ErbB signalling controls the dialogue between macrophages and neural crest-derived cells during zebrafish fin regeneration
Some fish can regenerate appendages by formation of a structure called the blastema. Here, the authors use single-cell RNA sequencing to characterize the cells required for blastema formation and fin regeneration and identified neural crest cells that orchestrate regeneration via the NRG1/ErbB axis
- Béryl Laplace-Builhé
- , Audrey Barthelaix
- & Farida Djouad
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Article
| Open Access
The serine proteases dipeptidyl-peptidase 4 and urokinase are key molecules in human and mouse scar formation
Mechanisms triggering hypertrophic scar formation remain poorly understood. Here the authors perform scRNA-seq on mature human hypertrophic scars and developing scars in mice to identify the serine proteases dipeptidyl-peptidase 4 and urokinase as key molecules in this process.
- Vera Vorstandlechner
- , Maria Laggner
- & Michael Mildner
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Article
| Open Access
Introducing dorsoventral patterning in adult regenerating lizard tails with gene-edited embryonic neural stem cells
Organisms with regenerative capacity typically regrow organs with correct axial patterning, however, regrown lizard tails lack this feature. Here the authors used neural stem cells to induce patterning in regenerating lizard tails and rescued normal skeletal morphology.
- Thomas P. Lozito
- , Ricardo Londono
- & Megan L. Hudnall
Annelid adult cell type diversity and their pluripotent cellular origins