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Article
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VGLL1 cooperates with TEAD4 to control human trophectoderm lineage specification
Authors report that VGLL1 regulates cell fate determination and self-renewal of human pluripotent stem cell-derived trophectoderm-like cells and trophoblast stem cells via modulation of chromatin accessibility in cooperation with TEAD4.
- Yueli Yang
- , Wenqi Jia
- & Wenjuan Li
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Article
| Open Access
Unique adipose tissue invariant natural killer T cell subpopulations control adipocyte turnover in mice
Invariant natural killer T (iNKT) cells have recently been reported to play a key role in adipose tissue homeostasis. Here, the authors show that adipose tissue iNKT cells mediate immune responses that control adipocyte turnover in mice.
- Sang Mun Han
- , Eun Seo Park
- & Jae Bum Kim
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Article
| Open Access
Clonal hematopoiesis related TET2 loss-of-function impedes IL1β-mediated epigenetic reprogramming in hematopoietic stem and progenitor cells
The expansion of cells with TET2 mutations within the blood is associated with increased risk for all-cause mortality, development of leukemia and cardiovascular disease. Here authors show IL1 promotes the clonal expansion TET2 knockout cells, enhancing their self-renewal, promoting their myeloid bias and impairing an IL1 driven loss of methylation at lymphoid and erythroid regulatory elements.
- J. McClatchy
- , R. Strogantsev
- & A. Agarwal
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Article
| Open Access
Intra- and inter-molecular regulation by intrinsically-disordered regions governs PUF protein RNA binding
FBF-2 and LST-1 repress gld-1 mRNA expression to maintain C. elegans germline stem cells. The authors show that an intrinsically-disordered region of FBF-2 autoinhibits its RNA binding. LST-1 antagonizes this interaction to promote RNA binding.
- Chen Qiu
- , Zihan Zhang
- & Traci M. Tanaka Hall
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Article
| Open Access
Optogenetic control of YAP reveals a dynamic communication code for stem cell fate and proliferation
The transcriptional regulator YAP controls cellular decisions such as proliferation, differentiation, and pluripotency. Here, the authors show a concentration-dependent and temporal communication code for YAP that enables cells to choose between these programs.
- Kirstin Meyer
- , Nicholas C. Lammers
- & Orion D. Weiner
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Article
| Open Access
SNIP1 and PRC2 coordinate cell fates of neural progenitors during brain development
The balance of stem cell maintenance, differentiation, and programmed death is critical for proper development. Here they show that SNIP1 is critical for stem cell survival and differentiation in the developing brain where it acts downstream of TGFb and NFkB and regulates PRC2 activities for governing cell fates.
- Yurika Matsui
- , Mohamed Nadhir Djekidel
- & Jamy C. Peng
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Article
| Open Access
RSL24D1 sustains steady-state ribosome biogenesis and pluripotency translational programs in embryonic stem cells
Pluripotency is coordinated at multiple levels of gene expression. Here the authors show that ribosome biogenesis is tightly regulated in embryonic stem cells (ESC) to control the translation of transcription and chromatin factors and dictate ESC fate.
- Sébastien Durand
- , Marion Bruelle
- & Mathieu Gabut
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Perspective
| Open Access
Molecular versatility during pluripotency progression
During development the embryo must balance lineage specification against the preservation of plasticity using a limited molecular toolkit. In this Perspective, the authors propose Molecular Versatility as a paradigm for grouping molecular mechanisms that are repurposed through development to exert distinct functions.
- Giacomo Furlan
- , Aurélia Huyghe
- & Fabrice Lavial
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Article
| Open Access
Alveolar cell fate selection and lifelong maintenance of AT2 cells by FGF signaling
Here the authors show that FGF signaling initiates alveolus development in mouse lung by inducing AT2 fate and a secondary signal for AT1 fate, and continuously maintains AT2 cells throughout life. FGF inhibition triggers immediate AT2 apoptosis and compensatory regeneration.
- Douglas G. Brownfield
- , Alex Diaz de Arce
- & Mark A. Krasnow
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Article
| Open Access
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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Article
| Open Access
ROR2 regulates self-renewal and maintenance of hair follicle stem cells
Wnt signaling functions in tissue homeostasis and tumorigenesis. Here the authors show that ROR2, a Wnt receptor, plays roles not only in transducing Wnt signaling, but also in regulation of DNA damage response critical for stem cell maintenance.
- Anthony Veltri
- , Christopher M. R. Lang
- & Wen-Hui Lien
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Article
| Open Access
Signal requirement for cortical potential of transplantable human neuroepithelial stem cells
The regulatory pathways that control the human neural progenitor cell pool are not well understood. Here, Varga et al. identify signals that control the division of human pluripotent stem cell derived neural stem cells and their ability to make cortical neurons and glia.
- Balazs V. Varga
- , Maryam Faiz
- & Andras Nagy
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Article
| Open Access
A genome-wide CRISPR-Cas9 knockout screen identifies essential and growth-restricting genes in human trophoblast stem cells
Here the authors perform a genome-wide CRISPR-Cas9 knockout screen to systematically identify and characterize essential and growth-restricting genes in human trophoblast cells. They identify TEAD1 as a key regulator that plays an important role in the specification, maintenance, and differentiation of the human trophoblast lineage by modulating chromatin architecture and gene expression.
- Chen Dong
- , Shuhua Fu
- & Thorold W. Theunissen
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Article
| Open Access
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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Article
| Open Access
Nuclear S-nitrosylation impacts tissue regeneration in zebrafish
The role of the post-translational modifications in tissue regeneration is still not clearly understood. Here, the authors show that many nuclear proteins change S-nitrosylation state in the regenerating zebrafish tailfin, highlighting the importance of Kdm1a S-nitrosylation in the repair process.
- Gianfranco Matrone
- , Sung Yun Jung
- & John P. Cooke
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Article
| Open Access
Joint single-cell multiomic analysis in Wnt3a induced asymmetric stem cell division
A localized Wnt3a signal has been shown to induce asymmetric division of mouse embryonic stem cells. Here the authors develop SET-seq, an approach to jointly profile epigenome and transcriptome in the same single cell and use it to provide mechanistic insights into the gene regulatory programs for maintaining and resetting stem cell fate during differentiation.
- Zhongxing Sun
- , Yin Tang
- & Dong Fang
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Article
| Open Access
Cell proliferation fate mapping reveals regional cardiomyocyte cell-cycle activity in subendocardial muscle of left ventricle
The adult mammalian heart exhibits stubbornly low levels of cardiomyocyte proliferation, leading to high morbidity after injury or heart attack. Here the authors develop an approach for tracking cardiomyocyte cell cycling and show that the majority are located adjacent to the endocardium.
- Xiuxiu Liu
- , Wenjuan Pu
- & Bin Zhou
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Article
| Open Access
HOXBLINC long non-coding RNA activation promotes leukemogenesis in NPM1-mutant acute myeloid leukemia
Nucleophosmin (NPM1) gene mutation induces a specific gene expression program leading to acute myeloid leukaemia. Here, the authors show that mutant NPM1 activates a HOXB locus-associated long non-coding RNA which is essential for its associated oncogenic transcriptional program and leukaemia development.
- Ganqian Zhu
- , Huacheng Luo
- & Mingjiang Xu
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Article
| Open Access
LIGHT/LTβR signaling regulates self-renewal and differentiation of hematopoietic and leukemia stem cells
Regulation of self-renewal is critical during steady state and stress in haematpoietic stem cells (HSCs), and underlies leukaemia pathology. Here, the authors show that LIGHT and its receptor LTβR promote quiescence and self-renewal of HSCs and that LTβR deficiency promotes survival in a mouse leukaemia model.
- S. S. Höpner
- , Ana Raykova
- & A. F. Ochsenbein
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Article
| Open Access
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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Article
| Open Access
Epidermal progenitors suppress GRHL3-mediated differentiation through intronic polyadenylation promoted by CPSF-HNRNPA3 collaboration
Suppression of terminal differentiation is essential for epidermal progenitor maintenance. Here, the authors show that intronic polyadenylation is dynamically regulated by the cooperation between CPSF and RNA-binding proteins to influence epidermal differentiation gene expression.
- Xin Chen
- , Sarah M. Lloyd
- & Xiaomin Bao
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Article
| Open Access
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
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Article
| Open Access
Unique properties of a subset of human pluripotent stem cells with high capacity for self-renewal
Human pluripotent cells (hPSCs) in standard culture are similar to mouse epiblast cells, but heterogeneity within hPSC cultures complicates comparisons. Here the authors show that a subpopulation of hPSCs enriched for self-renewal capacity have distinct cell cycle, metabolic, DNA methylation, and ATAC-seq profiles.
- Kevin X. Lau
- , Elizabeth A. Mason
- & Martin F. Pera
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Article
| Open Access
HyperTRIBE uncovers increased MUSASHI-2 RNA binding activity and differential regulation in leukemic stem cells
The identification of mRNA targets for RNA binding proteins (RBP) in stem cells is difficult due to the limited number of available cells. Here, as a proof-of-principle, the authors adapt the HyperTRIBE method to find that an RBP, MSI2, has increased RNA binding in leukemic compared with normal stem cells for selective regulation of oncogenic genes.
- Diu T. T. Nguyen
- , Yuheng Lu
- & Michael G. Kharas
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Article
| Open Access
IGF1-mediated human embryonic stem cell self-renewal recapitulates the embryonic niche
The signals regulating the establishment and maintenance of the pluripotent epiblast in human embryos are unclear. Here, the authors use a bioinformatics approach to identify the role of IGF1 in human embryo development, and from this, propose a culture medium with IGF1 together with Activin to sustain hESCs in the absence of FGF.
- Sissy E. Wamaitha
- , Katarzyna J. Grybel
- & Kathy K. Niakan
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Article
| Open Access
A transcriptome-wide antitermination mechanism sustaining identity of embryonic stem cells
Besides its role in splicing, U1 snRNP can suppress pre-mRNA cleavage and polyadenylation. The authors show that the nuclear cap-binding complex component Srrt/Ars2 maintains embryonic stem cell identity by promoting U1 recruitment to first introns and preventing premature termination of multiple transcripts.
- Yaroslav A. Kainov
- & Eugene V. Makeyev
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Article
| Open Access
Stem-cell-ubiquitous genes spatiotemporally coordinate division through regulation of stem-cell-specific gene networks
Stem-cell-specific genes regulate processes such as maintenance, identity and/or division. Here, the authors show that in the Arabidopsis root TCX2, a gene expressed across different stem cell populations (a stem-cell-ubiquitous gene), controls division and identity by regulating stem-cell-type-specific networks.
- Natalie M. Clark
- , Eli Buckner
- & Rossangela Sozzani
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Article
| Open Access
Procr-expressing progenitor cells are responsible for murine ovulatory rupture repair of ovarian surface epithelium
The ovary is covered by a surface epithelium (OSE) and cells mediating its repair post ovulation are unclear. Here, the authors identify the Protein C Receptor (Procr) as marking progenitor cells, distinct from Lgr5+ stem cells, on the murine surface epithelium that repair the OSE post ovulation.
- Jingqiang Wang
- , Daisong Wang
- & Yi Arial Zeng
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Article
| Open Access
IRF2 is a master regulator of human keratinocyte stem cell fate
Epidermal homeostasis requires long term stem cell function. Here, the authors apply transcriptional circuitry analysis based on integrated epigenomic profiling of primary human keratinocytes with high and low stem cell function to identify IRF2 as a negative regulator of stemness.
- Nicolas Mercado
- , Gabi Schutzius
- & Susan Kirkland
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Article
| Open Access
HNRNPK maintains epidermal progenitor function through transcription of proliferation genes and degrading differentiation promoting mRNAs
Maintenance of high turnover in tissues such as epidermis requires balance between proliferation and differentiation. Here the authors show that HNRNPK promotes RNA Polymerase II binding to proliferation and self-renewal genes as well as degradation of differentiation promoting mRNAs together with DDX6 in epidermis.
- Jingting Li
- , Yifang Chen
- & George L. Sen
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Article
| Open Access
YAP inhibition enhances the differentiation of functional stem cell-derived insulin-producing β cells
Pluripotent stem cells can be directed into insulin-producing beta cells in vitro. Here, the authors show that downregulation of YAP, an effector of the Hippo pathway, enhances endocrine progenitor differentiation and the generation of beta-cells with improved insulin secretion.
- Edwin A. Rosado-Olivieri
- , Kendall Anderson
- & Douglas A. Melton
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Article
| Open Access
Loss of BCL9/9l suppresses Wnt driven tumourigenesis in models that recapitulate human cancer
Whether the Wnt enhanceosome’ components BCL9/9l can affect intestinal homeostasis and tumorigenesis is still unclear. Using conditional Bcl9/9l KO mice, the authors of this study show that the BCL9/9l complex is required for intestinal stem cells to drive tissue regeneration and that loss of BCL9/9l suppresses Wnt-driven transformation.
- David M. Gay
- , Rachel A. Ridgway
- & Owen J. Sansom
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Article
| Open Access
Notch1 regulates the initiation of metastasis and self-renewal of Group 3 medulloblastoma
Group 3 medulloblastoma is an aggressive pediatric brain tumour that disseminates through the leptomeningeal cerebral spinal fluid. Here, the authors show that in Group 3 medulloblastoma NOTCH1 activates BMI1 through the activation of TWIST1, driving metastasis and self-renewal, and in mouse models a NOTCH1 blocking antibody decreased spinal metastases.
- Suzana A. Kahn
- , Xin Wang
- & Samuel H. Cheshier
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Article
| Open Access
Induction of muscle stem cell quiescence by the secreted niche factor Oncostatin M
The factors that mediate quiescence of muscle stem cells are unknown. The authors show that Oncostatin M is produced by skeletal muscle, suppresses stem cell proliferation, and that its deletion in muscle results in stem cell depletion and impaired muscle regeneration following injury in mice.
- Srinath C. Sampath
- , Srihari C. Sampath
- & Helen M. Blau
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Article
| Open Access
Basal lamina remodeling at the skeletal muscle stem cell niche mediates stem cell self-renewal
Extracellular matrix (ECM) remodelling is thought to have effects on muscle stem cells that support muscle homeostasis. Here the authors show ECM remodeling controls satellite cell self-renewal through deposition of laminin-α1 into the satellite cell niche.
- Shantisree Sandeepani Rayagiri
- , Daniele Ranaldi
- & Anne-Gaëlle Borycki
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Article
| Open Access
Cx26 drives self-renewal in triple-negative breast cancer via interaction with NANOG and focal adhesion kinase
Connexin proteins are usually considered as tumor suppressors. Here, the authors show that connexin 26 (Cx26) regulates the self-renewal of breast cancer stem cells via a ternary complex with FAK and NANOG.
- Praveena S. Thiagarajan
- , Maksim Sinyuk
- & Justin D. Lathia
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Article
| Open Access
DIP1 modulates stem cell homeostasis in Drosophila through regulation of sisR-1
Stable intronic sequence RNAs (sisRNAs) are by-products of splicing from introns with roles in embryonic development in Drosophila. Here, the authors show that the RNA binding protein DIP1 regulates sisRNAs in Drosophila, which is necessary for germline stem cell homeostasis.
- Jing Ting Wong
- , Farzanah Akhbar
- & Jun Wei Pek
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Article
| Open Access
Essential role of FBXL5-mediated cellular iron homeostasis in maintenance of hematopoietic stem cells
The iron-regulated F-box protein FBXL5 regulates iron homeostasis by mediating the degradation of iron regulatory protein 2 (IRP2). Here the authors show that FBXL5 and its regulation of IRP2 are required for HSC self-renewal and reconstitution capability.
- Yoshiharu Muto
- , Masaaki Nishiyama
- & Keiichi I. Nakayama
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Article
| Open Access
WNT10A mutation causes ectodermal dysplasia by impairing progenitor cell proliferation and KLF4-mediated differentiation
Human WNT10A mutations are associated with dental defects and adult onset ectodermal dysplasia. Xuet al. show that WNT10A-activated ß-catenin plays dual roles in adult epithelial progenitor proliferation and differentiation by complexing with KLF4 in differentiating, but not proliferating, cells.
- Mingang Xu
- , Jeremy Horrell
- & Sarah E. Millar
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Article
| Open Access
Lipid-mediated Wnt protein stabilization enables serum-free culture of human organ stem cells
There are two technical impediments for using purified Wnt proteins in serum-free stem cell cultures: rapid loss of activity and toxicity of detergents to stem cell self-renewal. Here, the authors show that lipid-stabilized Wnt3a can establish long-term culture of human intestinal and liver organoids.
- Nesrin Tüysüz
- , Louis van Bloois
- & Derk ten Berge
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Article
| Open Access
Long non-coding RNA GAS5 controls human embryonic stem cell self-renewal by maintaining NODAL signalling
Long non-coding RNAs (lncRNA) are known to regulate human embryonic stem cell (hESC) self-renewal. Here, the authors identify lncRNA growth-arrest-specific transcript 5 (GAS5) that regulates pluripotency via modulation of NODAL signalling to maintain self-renewal in hESCs.
- Chen Xu
- , Yan Zhang
- & Houqi Liu
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Article
| Open Access
Specification of haematopoietic stem cell fate via modulation of mitochondrial activity
Haematopoietic stem cells rely on glycolysis for their energy demands but whether this affects their fate is unknown. Here, the authors show that forcing the cells to rely on glycolysis is important for self-renewal and that this involves a reduction in mitochondrial mass.
- Nicola Vannini
- , Mukul Girotra
- & Matthias P. Lutolf
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Article
| Open Access
KRT14 marks a subpopulation of bladder basal cells with pivotal role in regeneration and tumorigenesis
It is unclear whether there is a progenitor/stem cell in the basal layer of the urothelium in the bladder. Here, the authors identify Keratin14 positive cells that can regenerate the bladder in both a natural and injury-induced manner, and following neoplastic transformation, can give rise to tumours.
- George Papafotiou
- , Varvara Paraskevopoulou
- & Apostolos Klinakis
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Article
| Open Access
Long-lived self-renewing bone marrow-derived macrophages displace embryo-derived cells to inhabit adult serous cavities
Understanding the heterogeneity of peritoneal macrophages is hampered by controversy over their origin and homeostasis. Here the authors show the embryonic F4/80hi population is replaced over time by self-renewing bone marrow-derived cells transitioning from F4/80lo to F4/80hi in adult mice, and that such turnover is more rapid in male mice.
- Calum C. Bain
- , Catherine A. Hawley
- & Stephen J. Jenkins
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Article
| Open Access
Downregulation of TLX induces TET3 expression and inhibits glioblastoma stem cell self-renewal and tumorigenesis
TLX is a nuclear receptor essential for neural stem cell self-renewal and recently involved in glioblastoma development. In this study, the authors show that inhibition of TLX expression, achieved using a dendrimer nanovector-delivered siRNAs or viral vector-delivered shRNAs, reduces glioblastoma stem cells self renewal and in vivotumour growth through activation of TET3.
- Qi Cui
- , Su Yang
- & Yanhong Shi
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Article
| Open Access
STAT5-regulated microRNA-193b controls haematopoietic stem and progenitor cell expansion by modulating cytokine receptor signalling
MicroRNAs regulate haematopoietic stem cell (HSC) development to ensure the correct generation of blood cells. Haetscher et al. show in mice that miR-193b controls the life-long self-renewal ability of HSCs via AKT and STAT5 pathways, with loss of miR-193b accelerating HSC expansion and reducing differentiation.
- Nadine Haetscher
- , Yonatan Feuermann
- & Michael A. Rieger
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Article
| Open Access
Histone H1-mediated epigenetic regulation controls germline stem cell self-renewal by modulating H4K16 acetylation
Epigenetics plays critical roles in controlling stem cell self-renewal and differentiation. Here, Sun et al. show that H1 is intrinsically required in the regulation of germline stem cells in the Drosophilaovary by antagonizing MOF, a histone acetyltransferase specific for H4K16.
- Jin Sun
- , Hui-Min Wei
- & Jian-Quan Ni
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Article
| Open Access
Fgf and Esrrb integrate epigenetic and transcriptional networks that regulate self-renewal of trophoblast stem cells
The transcription factor estrogen-related receptor beta, Esrrb, regulates pluripotency genes in embryonic stem cells, but how it acts in trophoblast stem (TS) cells is unclear. Here, the authors identify Esrrb as a primary target of Fgf/Mek signaling and outline a unique TS cell-specific interactome to sustain stemness.
- Paulina A. Latos
- , Angela Goncalves
- & Myriam Hemberger
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Article
| Open Access
Epigenetic silencing of Oct4 by a complex containing SUV39H1 and Oct4 pseudogene lncRNA
Pseudogene derived long non-coding RNAs (lncRNAs) can regulate the expression of their ancestral genes. Here, the authors show that the Oct4 pseudogene OctP4lncRNA plays an important role in inducing and maintaining silencing of the ancestral Oct4 gene in differentiating mouse embryonic stem cells.
- Michele Scarola
- , Elisa Comisso
- & Roberta Benetti
The PTM profiling of CTCF reveals the regulation of 3D chromatin structure by O-GlcNAcylation