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Decoding spatiotemporal transcriptional dynamics and epithelial fibroblast crosstalk during gastroesophageal junction development through single cell analysis
Elucidating the gastroesophageal junction’s development is key to comprehending its disease susceptibility. Here, the authors mapped its development, uncovering cellular diversity and interaction dynamics using advanced spatiotemporal single-cell analysis.
- Naveen Kumar
- , Pon Ganish Prakash
- & Cindrilla Chumduri
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| Open Access
Neurofibromin 1 controls metabolic balance and Notch-dependent quiescence of murine juvenile myogenic progenitors
The establishment of the postnatal skeletal muscle stem cell pool is not well understood. Here the authors show a requirement for Nf1 to coordinate muscle fiber growth and stem cell quiescence induction, and to prevent detrimental metabolic reprogramming with life-long consequences.
- Xiaoyan Wei
- , Angelos Rigopoulos
- & Sigmar Stricker
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Diffusible fraction of niche BMP ligand safeguards stem-cell differentiation
The activity of Drosophila male germline stem cells is tightly regulated by a cluster of somatic niche cells. Here they find that Dpp induces opposed cellular responses in stem cells versus in differentiating descendants, thereby ensuring spatial control of the niche with a single factor.
- Sharif M. Ridwan
- , Autumn Twillie
- & Mayu Inaba
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Mcam inhibits macrophage-mediated development of mammary gland through non-canonical Wnt signaling
Mammary epithelial cells act to continuously renew the mammary tissue and must balance differentiation and self-renewal. Here they show that Mcam, a non-canonical Wnt pathway member, regulates communication between macrophages and mammary epithelial cells, thereby maintaining self-renewal and subsequently promoting mammary ductal morphogenesis.
- Xing Yang
- , Haibo Xu
- & Baowei Jiao
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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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| Open Access
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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Ebf3+ niche-derived CXCL12 is required for the localization and maintenance of hematopoietic stem cells
CAR cells act as HSC niche cells. Here the authors show that CXCL12 ablation in half CAR cells attracts HSCs from affected CAR cells to intact CAR cells whereas CXCL12 ablation in all CAR cells depletes balanced HSCs producing B cells at high levels.
- Taichi Nakatani
- , Tatsuki Sugiyama
- & Takashi Nagasawa
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FGFR2 is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation
Restoring salivary acinar cells after gland damage is a major clinical challenge. Here, authors identify FGF7-FGFR2-MAPK signaling as a regenerative target, critical for myoepithelial-acinar crosstalk that regulates seromucous acinar differentiation.
- Marit H. Aure
- , Jennifer M. Symonds
- & Matthew P. Hoffman
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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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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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| Open Access
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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Cyclical dermal micro-niche switching governs the morphological infradian rhythm of mouse zigzag hair
Biological rhythms influence physiology and morphogenesis, though how these influence periodic pattern formation remains unclear. Here the authors show that the infradian rhythm observed in zigzag hairs is regulated by hair progenitors and their micro-niche and influences hair shaft bending.
- Makoto Takeo
- , Koh-ei Toyoshima
- & Takashi Tsuji
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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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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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Higher-order epistasis shapes natural variation in germ stem cell niche activity
Stem cell niches regulate proliferation of stem cells, but variation in this control across natural populations has not been explored. Here they combine quantitative genetics and gene editing to show that natural variation in C. elegans germ stem cell niche activity is shaped by complex gene-gene interactions.
- Sarah R. Fausett
- , Asma Sandjak
- & Christian Braendle
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Cellular population dynamics shape the route to human pluripotency
The contribution of cell-extrinsic factors during cellular reprogramming to human induced pluripotent stem cells has long been overlooked. Here, the authors show functional protein communication between reprogramming intermediates and the re-shaping of a permissive extracellular environment.
- Francesco Panariello
- , Onelia Gagliano
- & Nicola Elvassore
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A single-cell transcriptional atlas reveals resident progenitor cell niche functions in TMJ disc development and injury
The transcriptional network in TMJ disc development and injury remains poorly characterized. Here they generate a scRNA-seq atlas of mouse TMJ disc, and identify the resident progenitor population and how its transcriptional reprogramming contributes to disc repair.
- Ruiye Bi
- , Qing Yin
- & Songsong Zhu
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Epigenetic control of cellular crosstalk defines gastrointestinal organ fate and function
Mesenchymal-epithelial crosstalk plays a key role in gut development and stem cell homeostasis, though underlying mechanisms are still unclear. Here, the authors demonstrate that mesenchymal Polycomb Repressive Complex 2 controls niche signals for gut epithelial fate and growth.
- Ryan J. Smith
- , Minggao Liang
- & Tae-Hee Kim
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Integration of single-cell transcriptomes and biological function reveals distinct behavioral patterns in bone marrow endothelium
Here Kim et al. show that primary BMECs can be maintained ex vivo as distinct sinusoidal- and arterial-like populations and that the presence of macrophages is critical to preserve their native transcriptomic profiles and functional heterogeneity.
- Young-Woong Kim
- , Greta Zara
- & Nadia Carlesso
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Eya-controlled affinity between cell lineages drives tissue self-organization during Drosophila oogenesis
Oogenesis depends on close interaction between germ cells and the surrounding somatic niche. Here the authors demonstrate that Eya controls bilateral affinity at the germline-soma interface to generate self-organizing inter-lineage units that ensure oocyte maturation.
- Vanessa Weichselberger
- , Patrick Dondl
- & Anne-Kathrin Classen
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Murine fetal bone marrow does not support functional hematopoietic stem and progenitor cells until birth
Relatively little is known about the first hematopoietic stem and progenitor cells to arrive in the fetal bone marrow. Here they characterize the frequency, function, and molecular identity of fetal BM HSPCs and their bone marrow niche, and show that most BM HSPCs have little hematopoietic function until birth.
- Trent D. Hall
- , Hyunjin Kim
- & Shannon McKinney-Freeman
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An interplay between cellular growth and atypical fusion defines morphogenesis of a modular glial niche in Drosophila
Little is known of how the architectural complexity of the neural stem cell niche is achieved. Rujano et al. show that the morphogenesis of a glial niche in Drosophila involves complex proliferative strategies and atypical cell–cell fusion.
- Maria Alexandra Rujano
- , David Briand
- & Pauline Spéder
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Spatially resolved proteomic map shows that extracellular matrix regulates epidermal growth
Ling Leng et al. construct a hierarchical skin proteome map and identify an extracellular matrix glycoprotein TGFBI, which is located in basement membrane and could enhance the growth and function of epidermal stem cells and promote wound healing.
- Jun Li
- , Jie Ma
- & Ling Leng
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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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| Open Access
Runx1 and Runx2 inhibit fibrotic conversion of cellular niches for hematopoietic stem cells
The transcription factors, Runx1 and Runx2 are critical embryonically for generation of HSCs and osteoblasts, respectively. Here the authors show that adult mice lacking Runx1 and Runx2 in HSC-supporting CAR cells displayed an increase in fibrosis with reduced HSCs in bone marrow.
- Yoshiki Omatsu
- , Shota Aiba
- & Takashi Nagasawa
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Human pancreatic microenvironment promotes β-cell differentiation via non-canonical WNT5A/JNK and BMP signaling
In vitro differentiation of pancreatic beta cells offers a potential therapeutic approach for diabetes. Here they show human pluripotent stem cell derived pancreatic progenitors differentiate into insulin-secreting cells by crosstalk of WNT5A and BMP signaling.
- Jolanta Chmielowiec
- , Wojciech J. Szlachcic
- & Malgorzata Borowiak
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A specialized bone marrow microenvironment for fetal haematopoiesis
The colonization of bone marrow by haematopoietic stem and progenitor cells is critical for lifelong blood cell formation. Here the authors report distinct features of fetal bone marrow and show that artery-derived signals promote haematopoietic colonization.
- Yang Liu
- , Qi Chen
- & Ralf H. Adams
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Cytonemes coordinate asymmetric signaling and organization in the Drosophila muscle progenitor niche
Asymmetric signaling and organization in the stem cell niche determine cell fates. Here the authors show that polarized contact-dependent signaling through specialized cytonemes forms the basis of niche-specific asymmetric signaling and stem cell organization.
- Akshay Patel
- , Yicong Wu
- & Sougata Roy
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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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Quantification of bone marrow interstitial pH and calcium concentration by intravital ratiometric imaging
The fate of hematopoietic stem cells can be controlled by factors such as calcium ion concentration. Here the authors report an intravital ratiometric analysis method to measure extracellular calcium ion concentrations and absolute pH in mouse bone marrow.
- S-C. A. Yeh
- , J. Hou
- & C. P. Lin
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| Open Access
Bone marrow sinusoidal endothelium controls terminal erythroid differentiation and reticulocyte maturation
Niche crosstalk with Haematopoietic cells underlies normal haematopoiesis and myeloid disorders. Here the authors report a Stabilin2-Cre driver mouse with Cre-activity restricted to bone marrow sinusoidal endothelial cells, and that Stabilin2-Cre driven overactivation of b-catenin leads to erythroid differentiation defects and anaemia.
- Joschka Heil
- , Victor Olsavszky
- & Philipp-Sebastian Koch
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| 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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Progenitor translatome changes coordinated by Tsc1 increase perception of Wnt signals to end nephrogenesis
The cessation of nephrogenesis determines nephron endowments in mammals. Here the authors show that differential translation of Wnt antagonists versus agonists determines the tipping point from self-renewal to differentiation of nephron progenitors during nephrogenesis, using mutant mice with elevated nephron numbers.
- Alison E. Jarmas
- , Eric W. Brunskill
- & Raphael Kopan
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Quantitative 3D imaging of the cranial microvascular environment at single-cell resolution
Vascularization is critical for cranial bone growth, maintenance, and healing, but it remains unknown how blood vessels are spatially distributed in the calvarium, and how they interact with skeletal progenitors during these processes. Here, the authors apply a quantitative light-sheet imaging platform to visualize and analyze the relationship between blood vessels and skeletal progenitors throughout the murine calvarium.
- Alexandra N. Rindone
- , Xiaonan Liu
- & Warren L. Grayson
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| Open Access
Physiologic biomechanics enhance reproducible contractile development in a stem cell derived cardiac muscle platform
Investigations of human cardiac disease involving human pluripotent stem cell-derived cardiomyocytes are limited by the disorganized presentation of biomechanical cues resulting in cell immaturity. Here the authors develop a platform of micron-scale 2D cardiac muscle bundles to precisely deliver physiologic cues, improving reproducibility and throughput.
- Yao-Chang Tsan
- , Samuel J. DePalma
- & Adam S. Helms
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Niche derived netrin-1 regulates hematopoietic stem cell dormancy via its receptor neogenin-1
Haematopoietic stem cells (HSCs) are characterized by their self-renewal potential and associated dormancy. Here the authors show that niche produced netrin-1 preserves HSC quiescence and self-renewal via neogenin-1, and that decline of netrin-1 production during ageing leads to decreased Neo1 mediated HSC self-renewal.
- Simon Renders
- , Arthur Flohr Svendsen
- & Andreas Trumpp
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Single-cell analysis of developing and azoospermia human testicles reveals central role of Sertoli cells
Non-obstructive azoospermia affects 1% of men. Here, authors perform single-cell transcriptomic analysis of human testicular cells from healthy donors and non-obstructive azoospermia patients and find that inhibition of Wnt signaling promotes the maturation of Sertoli cells from patients.
- LiangYu Zhao
- , ChenCheng Yao
- & Zheng Li
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| Open Access
Fgf and Wnt signaling interaction in the mesenchymal niche regulates the murine hair cycle clock
The underlying mechanisms regulating the mouse hair cycle remain poorly understood. Here, the authors find that Fgf and Wnt signaling pathways interact in the mesenchymal niche of the hair follicle to regulate the molecular clock that dictates the duration of hair growth.
- Sarina Harshuk-Shabso
- , Hila Dressler
- & David Enshell-Seijffers
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| Open Access
Dental cell type atlas reveals stem and differentiated cell types in mouse and human teeth
Unlike human teeth, mouse incisors grow throughout life, based on stem and progenitor cell activity. Here the authors generate single cell RNA-seq comparative maps of continuously-growing mouse incisor, non-growing mouse molar and human teeth, combined with lineage tracing to reveal dental cell complexity.
- Jan Krivanek
- , Ruslan A. Soldatov
- & Igor Adameyko
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| Open Access
Mechano-modulatory synthetic niches for liver organoid derivation
3D liver organoids hold great promise for regenerative medicine but the use of ill-defined matrices limits their potential. Here, the authors generate human and mouse liver organoids using a chemically defined matrix, and reveal a link between matrix stiffness and organoid growth that does not require acto-myosin contraction.
- Giovanni Sorrentino
- , Saba Rezakhani
- & Kristina Schoonjans
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| Open Access
Long-term culture of human pancreatic slices as a model to study real-time islet regeneration
The ability to culture live pancreatic tissue slices for long periods of time would enable longitudinal studies ex vivo. Here the authors culture human and mouse pancreatic slices in a perfluorocarbon-based culture system and show stable endocrine and exocrine function for up to ten days in culture.
- Mirza Muhammad Fahd Qadir
- , Silvia Álvarez-Cubela
- & Juan Domínguez-Bendala
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| Open Access
Diaphanous-related formin mDia2 regulates beta2 integrins to control hematopoietic stem and progenitor cell engraftment
Bone marrow engraftment of haematopoietic stem and progenitor cells (HSPCs) requires homing and lodgement to the niche. Here, the authors show that mDia2 is required for HSPC polarization, nuclear MAL, and SRF-induced beta2 integrin expression during transendothelial migration of HSPCs required for engraftment.
- Yang Mei
- , Xu Han
- & Peng Ji
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Piwi reduction in the aged niche eliminates germline stem cells via Toll-GSK3 signaling
Retrotransposons are known to be involved in aging. Here the authors show that the retrotransposon silencer Piwi contributes to germline stem cell loss during aging in Drosophila.
- Kun-Yang Lin
- , Wen-Der Wang
- & Hwei-Jan Hsu
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| Open Access
Endothelin-1 signaling maintains glial progenitor proliferation in the postnatal subventricular zone
Endothelin-1 (ET-1) is a vasoconstrictor molecule that is also present in the developing and injured CNS. Here the authors show that ET-1 is present in the postnatal subventricular zone and acts to regulate maintenance and proliferation of radial glial cells and oligodendrocyte progenitor cells.
- Katrina L. Adams
- , Giulia Riparini
- & Vittorio Gallo
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| Open Access
Engineered niches support the development of human dendritic cells in humanized mice
Classical human dendritic cells (cDCs) are rare sentinel cells specialized in regulating adaptive immunity. Here, the authors show that expression of membrane bound FLT3L, along with stem cell factor (SCF) and CXCL12 in stromal cells induces specification of pre/AS-DCs, type 1 and type2 cDC from haematopoietic stem cells.
- Giorgio Anselmi
- , Kristine Vaivode
- & Pierre Guermonprez
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Ptch2/Gas1 and Ptch1/Boc differentially regulate Hedgehog signalling in murine primordial germ cell migration
How co-receptors Gas1 and Boc interact with Ptch1/2 receptors and regulate Hh signalling is unclear. Here, the authors demonstrate that the spatiotemporal expression of Gas1 and Boc determines how Hh signalling affects the dynamic migration of murine primordial germ cells.
- Yeonjoo Kim
- , Jiyoung Lee
- & Soo-Hyun Kim
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| Open Access
Single-cell analysis of human ovarian cortex identifies distinct cell populations but no oogonial stem cells
The outer lining or cortex of the human ovary determines fertility and has been postulated to contain oogonial stem cells. Here, the authors generate a single-cell map of the adult human ovarian cortex and show that DDX4 labels perivascular cells but no oogonial stem cells.
- Magdalena Wagner
- , Masahito Yoshihara
- & Pauliina Damdimopoulou
LSD1 drives intestinal epithelial maturation and controls small intestinal immune cell composition independent of microbiota in a murine model