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| Open AccessHepatocytes differentiate into intestinal epithelial cells through a hybrid epithelial/mesenchymal cell state in culture
Hepatocytes dedifferentiate into progenitor-like cells in culture. Here, authors elucidate the dynamics and mechanisms of hepatocyte dedifferentiation and find an unexpected differentiation potential of hepatocytes into intestinal epithelial cells.
- Shizuka Miura
- , Kenichi Horisawa
- & Atsushi Suzuki
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Article
| Open AccessComplete male-to-female sex reversal in XY mice lacking the miR-17~92 cluster
The cluster miR-17~92 modulates the expression of genes networks and signalling pathways to ensure proper Sry expression timing and subsequent testis differentiation, an unexpected role for miRNAs in the early steps of mammalian sex determination.
- Alicia Hurtado
- , Irene Mota-Gómez
- & Francisco J. Barrionuevo
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Article
| Open AccessCell-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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Article
| Open AccessReassessing 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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Article
| Open AccessCell diversity and plasticity during atrioventricular heart valve EMTs
Lotto et al. delineate cell diversity and mechanisms during heart valve development using scRNA-seq. They identify distinct cell types and states, the emergence of epithelial-mesenchymal plasticity, and cell interactions that may govern this process.
- Jeremy Lotto
- , Rebecca Cullum
- & Pamela A. Hoodless
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Article
| Open AccessAscl1 and Ngn2 convert mouse embryonic stem cells to neurons via functionally distinct paths
Expression of transcription factors can convert one cell type to another beyond developmental paths. Here, the authors show that cells can take two mechanistically distinct paths in the same transition paradigm when driven by the similar proneural factors Ascl1 and Ngn2.
- Gintautas Vainorius
- , Maria Novatchkova
- & Ulrich Elling
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Article
| Open AccessMeis1 establishes the pre-hemogenic endothelial state prior to Runx1 expression
Hematopoietic stem cell formation via the endothelial-to-hematopoietic transition is initiated by a complex rewiring of the aortic endothelium. Here the authors identify Meis1 as an early driver of hemogenic specification of this arterial endothelium.
- Patrick Coulombe
- , Grace Cole
- & Aly Karsan
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Article
| Open AccessWound infiltrating adipocytes are not myofibroblasts
Adipocyte plasticity during injury repair is debated. Here, the authors find that injury causes temporary adipocyte migration, but without lineage conversion to myofibroblasts. Distinct migration patterns, transcriptomics and ECM depositions indicate that adipocytes, unlike fibroblasts, do not contribute to fibrotic scars.
- Shruthi Kalgudde Gopal
- , Ruoxuan Dai
- & Yuval Rinkevich
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Article
| Open AccessConserved transcription factors promote cell fate stability and restrict reprogramming potential in differentiated cells
Transdifferentiation has been proposed as an approach for regenerative medicine, but the mechanisms that safeguard cell identity are not well established. Here they identify transcription factors that oppose transdifferentiation and show that knockdown of these genes improves recovery after myocardial infarction.
- Maria A. Missinato
- , Sean Murphy
- & Alexandre R. Colas
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Article
| Open AccessA hierarchical transcription factor cascade regulates enteroendocrine cell diversity and plasticity in Drosophila
Here the authors elucidate a simple transcription factor code that underlies the complex genetic specification of enteroendocrine cell (EE) subtypes, and reveal significant cellular plasticity amongst EE subtypes.
- Xingting Guo
- , Yongchao Zhang
- & Rongwen Xi
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Article
| Open AccessTRIM28-dependent SUMOylation protects the adult ovary from activation of the testicular pathway
Gonadal fate in mammals is determined during embryogenesis and is actively maintained in adulthood. This study shows that E3-SUMO ligase activity of TRIM28 is required for ovarian identity maintenance and testicular-specific gene repression in mouse adult ovary; in its absence, ovarian granulosa cells transdifferentiate to Sertoli cells.
- Moïra Rossitto
- , Stephanie Déjardin
- & Francis Poulat
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| Open AccessSomatic cell fate maintenance in mouse fetal testes via autocrine/paracrine action of AMH and activin B
Fate determination and maintenance of foetal testes in most animals occurs cell autonomously. Here the authors show in mouse XY embryos that Sertoli cell derived AMH and activin B together maintain Sertoli cell identity, and lack of both AMH and activin B leads to transdifferentiation into female granulosa cells.
- Karina F. Rodriguez
- , Paula R. Brown
- & Humphrey Hung-Chang Yao
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Article
| Open AccessFibroblast fusion to the muscle fiber regulates myotendinous junction formation
Classically, myogenic precursor cells derive from somites, and connective tissues derive from lateral plate mesoderm (LPM). Here the authors identify LPM derived fibroblasts that turn on a myogenic program and fuse to muscle fibers at muscle-tendon junctions, introducing fibroblast transcripts into myofibers.
- Wesal Yaseen
- , Ortal Kraft-Sheleg
- & Peleg Hasson
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Article
| Open AccessNotch2-mediated plasticity between marginal zone and follicular B cells
Notch signalling is central to marginal zone B cell development, but it is unclear what path this development takes in vivo. Here the authors use a mouse that lacks these cells to show that transgenic induction of Notch2 is sufficient for development of marginal zone B cells via transdifferentiation from follicular B cells and that this mechanism can occur in wildtype mice.
- Markus Lechner
- , Thomas Engleitner
- & Ursula Zimber-Strobl
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Article
| Open AccessTFEB regulates murine liver cell fate during development and regeneration
The Transcription Factor EB (TFEB) is known to regulate cellular homeostasis and energy metabolism, but its role in cell fate determination in the liver is unknown. Here, the authors show that TFEB regulates the progenitor/cholangiocyte lineage and that its depletion prevents tissue recovery upon injury.
- Nunzia Pastore
- , Tuong Huynh
- & Andrea Ballabio
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Article
| Open AccessA Wnt-mediated transformation of the bone marrow stromal cell identity orchestrates skeletal regeneration
Bone marrow stromal cells (BMSCs) lining sinusoidal blood vessels are mesenchymal cells whose function is critical for the skeleton. Here the authors show that quiescent CXCL12-expressing BMSCs can convert into a skeletal stem cell-like state, and differentiate into cortical bone osteoblasts only in response to injury.
- Yuki Matsushita
- , Mizuki Nagata
- & Noriaki Ono
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Article
| Open AccessA stably self-renewing adult blood-derived induced neural stem cell exhibiting patternability and epigenetic rejuvenation
Induced neurons, but not induced pluripotent stem cell (iPSC)-derived neurons, preserve age-related traits. Here, the authors demonstrate that blood-derived induced neural stem cells (iNSCs), despite lacking a pluripotency transit, lose age-related signatures.
- Chao Sheng
- , Johannes Jungverdorben
- & Oliver Brüstle
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Article
| Open AccessStepwise reprogramming of liver cells to a pancreas progenitor state by the transcriptional regulator Tgif2
Liver and pancreas cells arise from a common endoderm progenitor in the embryo, but what regulates their cell fate is unclear. Here, the authors show that expression of the Three-Amino-acid-Loop-Extension (TALE) homeobox TG-interacting factor 2 (TGIF2) in hepatocytes reprogrammes the cells to a pancreatic fate.
- Nuria Cerdá-Esteban
- , Heike Naumann
- & Francesca M. Spagnoli
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Article
| Open AccessTwo factor-based reprogramming of rodent and human fibroblasts into Schwann cells
Schwann cells (SCs) myelinate peripheral nerve axons and offer opportunities for the treatment of injuries and demyelinating diseases but reliable and renewable sources of these cells are hard to come by. Here the authors reprogram rat, mouse and human fibroblasts into Schwann cells using two transcription factors.
- Pietro Giuseppe Mazzara
- , Luca Massimino
- & Vania Broccoli
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Article
| Open AccessReprogramming mouse fibroblasts into engraftable myeloerythroid and lymphoid progenitors
Direct reprogramming of closely-related lineages can generate hematopoietic stem cells. Here, the authors show hematopoietic transcription factors Scl, Lmo2, Runx1 and Bmi1 can reprogram fibroblasts into induced hematopoietic progenitors (iHPs), which are engraftable blood progenitors.
- Hui Cheng
- , Heather Yin-Kuan Ang
- & Bing Lim
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Article
| Open AccessCell cycle and p53 gate the direct conversion of human fibroblasts to dopaminergic neurons
The efficiency of reprogramming of fibroblasts into induced dopaminergic neurons is often low. Here, Jiang et al.demonstrate increased transdifferentiation rates by inducing cell cycle arrest, suppressing p53, Tet 1 and by adding neurotrophic factors to the media.
- Houbo Jiang
- , Zhimin Xu
- & Jian Feng
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Cochlear supporting cell transdifferentiation and integration into hair cell layers by inhibition of ephrin-B2 signalling
Cochlear sensory hair cells produced during development are not replaced after loss so converting the surrounding supporting cells into hair cells could be a potential regenerative strategy. Here the authors show that hair cells can be directly generated from adjacent supporting cells in developing mouse embryos by inhibition of ephrin-B2 signalling.
- Jean Defourny
- , Susana Mateo Sánchez
- & Brigitte Malgrange
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Lgr5+ cells regenerate hair cells via proliferation and direct transdifferentiation in damaged neonatal mouse utricle
The balancing apparatus of the inner ear relies on the mechanosensory activity of hair cells (HC), which are poorly regenerated upon loss in adult mammals. Here, the authors show that in newborn mice HC regenerate through proliferation and transdifferentiation of activated striolar supporting cells that express Lgr5.
- Tian Wang
- , Renjie Chai
- & Alan G. Cheng
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Twist1 induces endothelial differentiation of tumour cells through the Jagged1-KLF4 axis
Tumour angiogenesis is critical for tumour growth and metastasis but the mechanisms that promote the growth of new blood vessels by tumours are not completely clear. Here the authors show that overexpression of the transcription factor Twist1 in certain tumour cells can lead them to differentiate into endothelial cells.
- Hsiao-Fan Chen
- , Chi-Hung Huang
- & Kou-Juey Wu
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YAP inhibits squamous transdifferentiation of Lkb1-deficient lung adenocarcinoma through ZEB2-dependent DNp63 repression
Lung adenocarcinomas can convert to squamous cell carcinomas, which is associated with cancer progression and therapy resistance. Here, Gao et al. identify YAP as an essential barrier for this phenotypic conversion through ZEB2-mediated DNP63 repression.
- Yijun Gao
- , Wenjing Zhang
- & Hongbin Ji
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Article
| Open AccessTransdifferentiation of lung adenocarcinoma in mice with Lkb1 deficiency to squamous cell carcinoma
Non-small cell lung cancer manifests as adenocarcinoma and squamous cell carcinoma but tumours of mixed lineage are often found in humans. Here, the authors show that adenocarcinoma can transdifferentiate into squamous cell carcinomas in mice.
- Xiangkun Han
- , Fuming Li
- & Hongbin Ji
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Transdifferentiation of parathyroid cells into cervical thymi promotes atypical T-cell development
Cervical thymi are secondary sites of T-cell development in mice. Here, the authors investigate previously unknown origin of cervical thymi and show that they develop as a by-product of the normal separation of thymic and parathyroid tissue.
- Jie Li
- , Zhijie Liu
- & Nancy R. Manley