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Cell-fate conversion of intestinal cells in adult Drosophila midgut by depleting a single transcription factor
The mechanisms underlying cell plasticity remain poorly understood. Here, Guo et.al discover that intestinal cells in the fly gut can alter their fates through the loss of a single gene, and identify several molecular barriers to cell reprogramming.
- Xingting Guo
- , Chenhui Wang
- & Rongwen Xi
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Polycomb-mediated silencing of miR-8 is required for maintenance of intestinal stemness in Drosophila melanogaster
Intestinal physiology requires a balance between stem cell self-renewal and differentiation. Here, the authors show that this balance is regulated epigenetically by a dynamic relationship between the evolutionarily conserved PRC2, miR-8 and Notch signaling.
- Zoe Veneti
- , Virginia Fasoulaki
- & Aristides G. Eliopoulos
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Sexual dimorphism in melanocyte stem cell behavior reveals combinational therapeutic strategies for cutaneous repigmentation
Vitiligo is an autoimmune condition that results in skin depigmentation due to melanocyte loss, but the root causes are not well understood. Here they identify sexual dimorphism in melanocyte stem cells behavior arising from distinct skin inflammatory responses, and propose Prostaglandin E2 as a potential therapy for depigmentation conditions.
- Luye An
- , Dahihm Kim
- & Andrew C. White
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LNP-RNA-engineered adipose stem cells for accelerated diabetic wound healing
Adipose stem cells are promising therapeutic agents in tissue regeneration. Here the authors develop a lipid nanoparticle/RNA engineering platform to enhance the protein production of these cells, which demonstrate superior healing efficacy in a mouse model of diabetic cutaneous wounds.
- Yonger Xue
- , Yuebao Zhang
- & Yizhou Dong
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The single-cell transcriptomic atlas and RORA-mediated 3D epigenomic remodeling in driving corneal epithelial differentiation
Ocular homeostasis and vision depend on the differentiation of limbal stem/progenitor cells into corneal epithelial cells. Here, the authors report transcriptional dynamics and RORA-mediated epigenetic remodeling underlying the differentiation of human corneal epithelium.
- Mingsen Li
- , Huizhen Guo
- & Hong Ouyang
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Adult stem cell activity in naked mole rats for long-term tissue maintenance
Authors report that long-term intestinal tissue maintenance in naked mole rats is achieved by having an expanded pool of slow-dividing adult stem cells while a higher proportion of differentiated cells confer enhanced function and protection to the intestinal mucosa.
- Shamir Montazid
- , Sheila Bandyopadhyay
- & Shazia Irshad
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Alveolar epithelial progenitor cells require Nkx2-1 to maintain progenitor-specific epigenomic state during lung homeostasis and regeneration
Alveolar epithelial progenitors in the lungs can regenerate the epithelial surface after acute injury. Here they generate lung organoids that can be used to study lung regeneration after injury and identify Nkx2-1 as a key regulator of alveolar progenitor activation.
- Andrea Toth
- , Paranthaman Kannan
- & William J. Zacharias
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Role of PDGFRA+ cells and a CD55+ PDGFRALo fraction in the gastric mesenchymal niche
Digestive epithelia self-renew or differentiate in response to mesenchymal cues. Manieri et al. characterize gastric corpus and antral mesenchyme separately and identify PDGFRALo CD55+ cells as those selectively supporting epithelial growth in vitro.
- Elisa Manieri
- , Guodong Tie
- & Ramesh A. Shivdasani
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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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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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Hierarchical assembly of tryptophan zipper peptides into stress-relaxing bioactive hydrogels
Rational design has endowed self-assembling peptides with structural similarities to natural materials, but recreating the dynamic functional properties inherent to natural systems remains challenging. Here the authors report the discovery of a short peptide based on the tryptophan zipper motif, that shows multiscale hierarchical ordering into hydrogels that display emergent dynamic properties.
- Ashley K. Nguyen
- , Thomas G. Molley
- & Kristopher A. Kilian
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Phase separation of BuGZ regulates gut regeneration and aging through interaction with m6A regulators
Phase separation serves to compartmentalize and concentrate cellular components to facilitate essential physiological processes. Here, the authors elucidate the role and mechanism of BuGZ-mediated phase separation in the context of gut regeneration and aging.
- Qiaoqiao Zhang
- , Kai Deng
- & Hao Jiang
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Autocrine TGF-β-positive feedback in profibrotic AT2-lineage cells plays a crucial role in non-inflammatory lung fibrogenesis
IPF is a progressive disease with few inflammatory pathology. Here, using alveolar organoid technology, the authors identified autocrine TGF-β-positive feedback in AT2-lineage cells as a core mechanism of inflammation-independent lung fibrogenesis.
- Yasunori Enomoto
- , Hiroaki Katsura
- & Mitsuru Morimoto
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Single-cell transcriptomics uncovers EGFR signaling-mediated gastric progenitor cell differentiation in stomach homeostasis
Gastric progenitor cells are essential for tissue homeostasis of the stomach. Here, using single-cell RNA sequencing and gastric organoid experiments, the authors demonstrate that EGFR signaling promotes gastric progenitor cell differentiation.
- Hitomi Takada
- , Yohei Sasagawa
- & Akira Kurisaki
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Intracellular pH dynamics regulates intestinal stem cell lineage specification
Myriad extracellular and intracellular cues regulate stem cell fate choice. Here, Liu et al. report intracellular pH dynamics as a previously unrecognized regulator to selectively mediate the secretory cell fate decision of the intestinal stem cell.
- Yi Liu
- , Efren Reyes
- & Diane L. Barber
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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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DRAG in situ barcoding reveals an increased number of HSPCs contributing to myelopoiesis with age
Using in situ single cell lineage tracing technology DRAG, we show that, unlike emergency myelopoiesis post-transplantation, aged HSPCs do not functionally decline in the number of myeloid cells that they produce.
- Jos Urbanus
- , Jason Cosgrove
- & Leïla Perié
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WHIM Syndrome-linked CXCR4 mutations drive osteoporosis
Using a mouse model harboring a WHIM Syndrome-linked gain-of-function CXCR4 mutation and bone marrow samples from WHIM patients, the authors show that proper CXCR4 signaling termination is essential for bone tissue homeostasis.
- Adrienne Anginot
- , Julie Nguyen
- & Karl Balabanian
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Base-editing-mediated dissection of a γ-globin cis-regulatory element for the therapeutic reactivation of fetal hemoglobin expression
Antoniou and colleagues used base editing to generate a variety of mutations inducing γ-globin and rescue the β-hemoglobinopathy phenotype. This strategy was safe and effective in long-term repopulating hematopoietic stem/progenitor cells.
- Panagiotis Antoniou
- , Giulia Hardouin
- & Annarita Miccio
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Sexually dimorphic estrogen sensing in skeletal stem cells controls skeletal regeneration
How bone-related sexually dimorphic traits are regulated hasn’t been examined at the stem cell level. Here the authors show that skeletal stem cells (SSC), in female but not male mice, are directly controlled by estrogen signaling, which could be augmented to improve fracture repair.
- Tom W. Andrew
- , Lauren S. Koepke
- & Charles K. F. Chan
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Common anti-cancer therapies induce somatic mutations in stem cells of healthy tissue
Specific anti-cancer therapies are highly mutagenic to cancer cells but the mutational impact on healthy tissues remains elusive. Here, the authors use organoids and whole-genome sequencing to characterise somatic mutations in healthy colon and liver adult stem cells after chemo- or radiotherapy.
- Ewart Kuijk
- , Onno Kranenburg
- & Arne Van Hoeck
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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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Fate mapping of hematopoietic stem cells reveals two pathways of native thrombopoiesis
Hematopoietic stem cells produce diverse cell lineages. Here, the authors apply single-cell RNA-seq, computational integration of non-perturbative approaches for fate-mapping, and mitotic tracking to chart lineage decisions in native hematopoiesis and identify megakaryocyte progenitors that directly link HSCs to megakaryocytes.
- Mina N. F. Morcos
- , Congxin Li
- & Alexander Gerbaulet
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Salivary gland organoid culture maintains distinct glandular properties of murine and human major salivary glands
The long-term maintenance of diverse salivary gland cells remains challenging. Here the authors establish a protocol for long-term maintenance of murine and human salivary gland organoids exhibiting gland-specific gene expression, gland functions, and cellular diversity confirmed by scRNA-seq.
- Yeo-Jun Yoon
- , Donghyun Kim
- & Jae-Yol Lim
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Epigenetic traits inscribed in chromatin accessibility in aged hematopoietic stem cells
Haematopoietic stem cells (HSCs) exhibit considerable cell-intrinsic changes with age. Here the authors demonstrate that differentially accessible regions in aged HSC chromatin are enriched for stress-responsive enhancers and act as an epigenetic hub to augment transcriptional responses of aged HSCs to external stimuli.
- Naoki Itokawa
- , Motohiko Oshima
- & Atsushi Iwama
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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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Single cell analyses identify a highly regenerative and homogenous human CD34+ hematopoietic stem cell population
The trajectories of hematopoietic stem cells (HSCs) during lineage commitment are complex. Here, the authors use single cell RNA-sequencing and xenotransplantation to uncover CD34 + EPCR + (CD38/CD45RA)- HSCs, which high repopulating and self-renewal properties.
- Fernando Anjos-Afonso
- , Florian Buettner
- & Dominique Bonnet
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Tissue extracellular matrix hydrogels as alternatives to Matrigel for culturing gastrointestinal organoids
The culture of gastrointestinal organoids relies on Matrigel that has several drawbacks for clinical application. Here, the authors report the feasibility of gastrointestinal tissue-mimetic matrices as effective alternatives to Matrigel for organoid culture and transplantation.
- Suran Kim
- , Sungjin Min
- & Seung-Woo Cho
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Functional antagonism between ΔNp63α and GCM1 regulates human trophoblast stemness and differentiation
Trophoblast stem cells can be derived from human blastocysts and first-trimester, but not term, cytotrophoblasts. Here the authors show that induction efficiency of cytotrophoblast is determined by antagonism between GCM1 and ΔNp63α and manipulating this antagonism facilitates derivation of TS cells from term placenta.
- Liang-Jie Wang
- , Chie-Pein Chen
- & Hungwen Chen
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BMP feed-forward loop promotes terminal differentiation in gastric glands and is interrupted by H. pylori-driven inflammation
Helicobacter pylori causes gastric inflammation, gland hyperplasia and is linked to gastric cancer. Here the authors identify a BMP feedback loop between the stomach epithelium and surrounding stroma that controls gland homeostasis and demonstrate its interruption upon infection with H. pylori.
- Marta Kapalczynska
- , Manqiang Lin
- & Michael Sigal
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Malfunction of airway basal stem cells plays a crucial role in pathophysiology of tracheobronchopathia osteoplastica
Tracheobronchopathia osteoplastica (TO), is an underreported affliction characterized by squamous metaplasia and heterotopic bone formation in trachea and bronchi. Here the authors apply functional, as well as genome-wide transcriptional and epigenetic profiling to identify airway basal cells dysfunction underlying TO.
- Yue Hong
- , Shan Shan
- & Tao Ren
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Comprehensive 3D epigenomic maps define limbal stem/progenitor cell function and identity
Genome topology provides a structural basis for epigenome-mediated transcriptional regulation in eukaryotes. Here the authors characterized the 3D genome of stratified squamous epithelia. They generated a Hi-C map of human limbal stem/progenitor cells (LSCs) and integrated these data with epigenomics, transcription factor binding maps, and transcriptome data.
- Mingsen Li
- , Huaxing Huang
- & Hong Ouyang
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Multi-modal profiling of human fetal liver hematopoietic stem cells reveals the molecular signature of engraftment
During human embryonic development, haematopoietic stem cells of the foetal liver undergo expansion, while retaining engraftment capacity. Here the authors apply CITE-seq to profile single cells from a human foetal liver, identifying a molecular signature of engraftment potential
- Kim Vanuytsel
- , Carlos Villacorta-Martin
- & George J. Murphy
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Modelling Chlamydia and HPV co-infection in patient-derived ectocervix organoids reveals distinct cellular reprogramming
Here, Koster et al., model human papillomavirus and Chlamydia coinfection dynamics in patient-derived ectocervical organoids, and characterize the effects of multiple infections in the cellular microenvironment, potentially contributing to neoplasia.
- Stefanie Koster
- , Rajendra Kumar Gurumurthy
- & Cindrilla Chumduri
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Single-cell profiling of human subventricular zone progenitors identifies SFRP1 as a target to re-activate progenitors
The decline in neurogenesis following birth is accompanied with a quiescent state characteristic of neural progenitors of the adult brain. Here, the authors identify the Wnt pathway antagonist SFRP1 as a potential signal that promotes quiescence and show that its inhibition stimulates stem cell activation.
- Vanessa Donega
- , Astrid T. van der Geest
- & Elly M. Hol
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Cholinergic signals preserve haematopoietic stem cell quiescence during regenerative haematopoiesis
The sympathetic nervous system has been shown to respond to stress and activate haematopoietic stem cells. Here they show that cholinergic signals in the bone marrow preserve haematopoietic stem cell quiescence and self-renewal under proliferative stress.
- Claire Fielding
- , Andrés García-García
- & Simón Méndez-Ferrer
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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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SARS-CoV-2 infection and replication in human gastric organoids
Several clinical reports have described gastrointestinal symptoms for COVID-19, though whether the virus can replicate within the stomach remains unclear. Here the authors generate gastric organoids from human biopsies and show that the virus can efficiently infect gastric epithelium, suggesting that the stomach might have an active role in fecal-oral transmission.
- Giovanni Giuseppe Giobbe
- , Francesco Bonfante
- & Paolo De Coppi
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p107 mediated mitochondrial function controls muscle stem cell proliferative fates
The connection between cell cycle, metabolic state and mitochondrial activity is unclear. Here, the authors show that p107 represses mitochondrial transcription and ATP output in response to glycolytic byproducts, causing metabolic control of the cell cycle rate in myogenic progenitors.
- Debasmita Bhattacharya
- , Vicky Shah
- & Anthony Scimè
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Multi-species single-cell transcriptomic analysis of ocular compartment regulons
A comprehensive analysis of the ocular networks among various tissues is necessary to understand eye physiology in health and disease. Here the authors present a multi-species single-cell transcriptomic atlas consisting of cells of the cornea, iris, ciliary body, neural retina, retinal pigmented epithelium, and choroid.
- Pradeep Gautam
- , Kiyofumi Hamashima
- & Yuin-Han Loh
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A CRISPR/Cas9 genetically engineered organoid biobank reveals essential host factors for coronaviruses
Rapid identification of host genes essential for virus replication may expedite the generation of therapeutic interventions. Here the authors generate mutant clonal intestinal organoids for 19 host genes previously implicated in coronavirus biology and identify the cell surface protease TMPRSS2 as a potential therapeutic target.
- Joep Beumer
- , Maarten H. Geurts
- & Hans Clevers
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Targeting local lymphatics to ameliorate heterotopic ossification via FGFR3-BMPR1a pathway
Different types of mesenchymal progenitors participate in ectopic bone formation. Here, the authors show Col2+ lineage cells adopt a lymphatic endothelium cell fate, which regulates local inflammatory microenvironment after trauma, thus influencing heterotopic ossification (HO) development via a FGFR3-BMPR1a pathway.
- Dali Zhang
- , Junlan Huang
- & Yangli Xie
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Establishment of a fluorescent reporter of RNA-polymerase II activity to identify dormant cells
The identification and characterisation of dormant cells is currently difficult. Here the authors report Optical Stem Cell Activity Reporter (OSCAR) to assess RNA polymerase II activity and identify dormant cell populations in intestinal epithelial cells in vivo.
- Rasmus Freter
- , Paola Falletta
- & Francesco Neri
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Acetylation of PAX7 controls muscle stem cell self-renewal and differentiation potential in mice
The acetyltransferase MYST1 stimulated by acetyl-CoA, and the deacetylase SIRT2 stimulated by NAD+, regulate PAX7 acetylation in muscle stem cells, which in turn, regulates stem cell self-renewal and regeneration following injury in mouse skeletal muscle.
- Marie-Claude Sincennes
- , Caroline E. Brun
- & Michael A. Rudnicki
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LRIG1 is a gatekeeper to exit from quiescence in adult neural stem cells
How neural stem cells can transition between states of proliferation and quiescence is unclear. Here, the authors identify Lrig1 as a specific marker for the primed quiescent state and demonstrate that Lrig1 maintains cells in a quiescent state via modulation of the EGFR pathway.
- María Ángeles Marqués-Torrejón
- , Charles A. C. Williams
- & Steven M. Pollard
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Single-keratinocyte transcriptomic analyses identify different clonal types and proliferative potential mediated by FOXM1 in human epidermal stem cells
Epidermal cultures can treat skin diseases, such as Junctional Epidermolysis Bullosa, but the signature of stem cells is unclear. By single cell RNAseq analyses on human keratinocytes, the authors identify the molecular profile of holoclones and the role of FOXM1 in regulating the proliferative potential of epidermal stem cells.
- Elena Enzo
- , Alessia Secone Seconetti
- & Michele De Luca
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Cellular stress signaling activates type-I IFN response through FOXO3-regulated lamin posttranslational modification
Neural stem and progenitor cells (NSPCs) encounter constant stresses during aging, such as elevated oxidative stress. Here the authors show that oxidative stress induced reduction in NSPC neural differentiation is mediated by a FOXO3-GNMT/SAM-lamin-cGAS/STING-IFN-I signalling cascade initiated by FOXO3 oxidation.
- Inah Hwang
- , Hiroki Uchida
- & Jihye Paik
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Core transcription regulatory circuitry orchestrates corneal epithelial homeostasis
Corneal epithelium shares similar molecular signatures to other stratified epithelia. Here, the authors map super-enhancers and accessible chromatin in corneal epithelium, identifying a transcription regulatory circuit, including RUNX1, PAX6, and SMAD3, required for corneal epithelial identity and homeostasis.
- Mingsen Li
- , Huaxing Huang
- & Hong Ouyang
Annelid adult cell type diversity and their pluripotent cellular origins