Circuit Design Features of a Stable Two-Cell System

Cell, Journal Year: 2018, Volume and Issue: 172(4), P. 744 - 757.e17

Published: Feb. 1, 2018

Language: Английский

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The never-ending story: from pluripotency to plant developmental plasticity

Development, Journal Year: 2015, Volume and Issue: 142(13), P. 2237 - 2249

Published: June 30, 2015

Plants are sessile organisms, some of which can live for over a thousand years. Unlike most animals, plants employ post-embryonic mode development driven by the continuous activity pluripotent stem cells. Consequently, able to initiate new organs extended periods time, and many species readily replace lost body structures de novo organogenesis. Classical studies have also shown that plant tissues remarkable capacity undergo de-differentiation proliferation in vitro, highlighting fact cell fate is highly plastic. This suggests mechanisms regulating transitions must be continuously active cells control cellular pluripotency lies at core diverse developmental programs. Here, we review how established systems, it maintained during growth re-initiated regeneration, these eventually contribute amazing plasticity plants.

Language: Английский

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What’s Luck Got to Do with It: Single Cells, Multiple Fates, and Biological Nondeterminism

Molecular Cell, Journal Year: 2016, Volume and Issue: 62(5), P. 788 - 802

Published: June 1, 2016

Language: Английский

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Signaling in the stem cell niche: regulating cell fate, function and plasticity

Development, Journal Year: 2018, Volume and Issue: 145(15)

Published: Aug. 1, 2018

ABSTRACT Stem cells have the ability to self-renew and differentiate along multiple lineages, driving tissue homeostasis regeneration. Paradigms of unidirectional, hierarchical differentiation trajectories observed in embryonic hematopoietic stem traditionally been applied tissue-resident cells. However, accumulating evidence implicates stemness as a bidirectional, dynamic state that is largely governed by niche, which facilitates plasticity adaptability changing conditions. In this Review, we discuss mechanisms cell fate regulation through niche-derived cues, with particular focus on epithelial mammalian skin, intestine lung. We spectrum biochemical, mechanical architectural inputs define states during morphogenesis, regeneration, highlight how these diverse influence plasticity.

Language: Английский

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Early stem cell aging in the mature brain

Cell stem cell, Journal Year: 2021, Volume and Issue: 28(5), P. 955 - 966.e7

Published: April 14, 2021

Language: Английский

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Competition for Mitogens Regulates Spermatogenic Stem Cell Homeostasis in an Open Niche

Cell stem cell, Journal Year: 2018, Volume and Issue: 24(1), P. 79 - 92.e6

Published: Dec. 20, 2018

Highlights•Mouse spermatogenic stem cells (SSCs) migrate among their differentiating progeny•Lymphatic endothelial near vasculature secrete FGFs that act as SSC mitogens•SSCs tune self-renewal and differentiation in response to FGF consumption•Competition for limited supply of mitogen (FGFs) regulates density homeostasisSummaryIn many tissues, homeostasis is maintained by physical contact between an anatomically defined niche. However, how cell achieved environments where are motile dispersed progeny remains unknown. Using murine spermatogenesis a model, we find tightly regulated the fibroblast growth factors from lymphatic cells. We propose through competition FGFs. show quantitative dependence on dosage, biased localization toward sources, dynamics during regeneration following injury can all be predicted explained within framework minimal theoretical model based "mitogen competition." this provides generic robust mechanism support open, or facultative, niche environments.Graphical abstract

Language: Английский

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Multiplicity of Mesenchymal Stromal Cells: Finding the Right Route to Therapy

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: May 16, 2019

Over the last decade, acceleration in clinical use of mesenchymal stromal cells (MSCs) has been nothing short spectacular. Perhaps most surprising is how little we know about "MSC product." Although MSCs are being delivered to patients at an alarming rate, regulatory requirements for MSC therapies (for example terms quality assurance and control) nowhere near expectations traditional pharmaceuticals. That said, standards that define a chemical compound or purified recombinant protein cannot be applied with same stringency cell-based therapy. Biological processes dynamic, adaptive variable. Heterogeneity will always exist emerge within even rigorously sorted clonal cell populations. With MSCs, perhaps more so than any other therapeutic cell, heterogeneity pervades multiple levels, from sample source single cell. The research communities collectively need recognize take steps address this troublesome truth, ensure promise MSC-based fulfilled.

Language: Английский

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Spermatogonial stem cells: updates from specification to clinical relevance

Human Reproduction Update, Journal Year: 2019, Volume and Issue: 25(3), P. 275 - 297

Published: Feb. 23, 2019

Human spermatogonia are target for exploration of adult stem cell characteristics and potential source the development therapeutic applications. Almost 50 years ago, Yves Clermont stated with regard to nature true cells: 'there is possibility that other classes exist beside three (Adark, Apale type B)…; …we still know too little about human spermatogonial cells'… This review seeks provide current knowledge, focusing on different aspects spermatogonia, novel information based species comparisons adaptation their proliferative potential. Moreover, objective an update state art concerning use clinical Germ specification mechanisms epigenetic as well transcriptional features primordial germ cells (PGC) at single-cell level reviewed. Studies analyses have been included they hitherto unequaled resolution profiles unselected testicular and, thereby, new insights into molecular differentiation. Datasets models expansion were identified turnover lifetime sperm production rates in various calculated, exclusively studies employing optical dissector approach. Finally, causes impaired function fertility preservation comprehensively RNA sequencing data from PGC indicate heterogeneity a feature prior Based these lineage-tracing it now debated whether rather plastic population undifferentiated niche being regulatory unit fate decisions. our calculations we suggest adapted individual reproductive lifespan life-long output spermatogonium balanced against duration generation. Thereby, risk jeopardizing genome integrity maximized output. With reference Clermont's statement, recent datasets, question needs be answered is: 'Is there cell?' or better distinct serving pool?'. provides including views biology (from embryonic stages). We consider this relevant all research scientists clinicians dealing fertility, spermatogenesis preservation.

Language: Английский

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De Novo Mutations Reflect Development and Aging of the Human Germline

Trends in Genetics, Journal Year: 2019, Volume and Issue: 35(11), P. 828 - 839

Published: Oct. 11, 2019

Both the age of father and mother are positively correlated with number de novo mutations (DNMs) in offspring, effect size paternal being larger.DNMs associated maternal aging each have unique mutational signatures based on their nucleotide substitution spectrum genomic locations.DNM clusters characteristics distinct from nonclustered DNMs, suggesting different underlying causes.Post-zygotic arising during early embryonic development a frequent phenomenon differ nonmosaic germline DNMs spectrum.A subset presumed can be traced back as low-level mosaic somatic tissue parent. These mutation recur future offspring. Human both driver evolution an important cause genetic diseases. In past few years, whole-genome sequencing (WGS) parent–offspring trios has facilitated large-scale detection study human which led to exciting discoveries. The overarching theme all these studies is that individual complex mixture arise through biological processes acting at times life. (DNMs, see Glossary) newly occurred within one generation. While vast majority genome been inherited earlier generations, provide new variation. consequences vary widely. neutral or advantageous might become established our species thereby contribute evolution, changes crucial sequences also result misfunctioning systems, resulting severe disease. One earliest known examples this was Down syndrome, caused by trisomy chromosome 21 [1Davenport C.B. Mendelism man.in: Proceedings Sixth International Congress Genetics. 1932http://www.esp.org/books/6th-congress/facsimile/contents/6th-cong-p135-davenport.pdfGoogle Scholar, 2Allen G. Aetiology Down's syndrome inferred Waardenburg 1932.Nature. 1974; 250: 436-437Crossref PubMed Scopus (8) Google 3Lejeune J. et al.[Study chromosomes 9 mongoloid children].C. R. Hebd. Seances Acad. Sci. 1959; 248 (in French): 1721-1722PubMed Scholar]. recent years found prominent neurodevelopmental diseases, including intellectual disability, autism, schizophrenia [4Veltman J.A. Brunner H.G. De disease.Nat. Rev. Genet. 2012; 13: 565-575Crossref (478) 5Acuna-Hidalgo al.New insights into generation role health disease.Genome Biol. 2016; 17: 241Crossref (162) unbiased point humans for many hampered lack techniques scan entire cost-effective way. introduction next-generation (NGS) technologies spurred investigations [6Koboldt D.C. al.The revolution its impact genomics.Cell. 2013; 155: 27-38Abstract Full Text PDF (556) refer variety types, such single-nucleotide substitutions, insertions, deletions, copy-number variants (CNVs). review we focus progress made field since WGS, exploring biology possible mechanisms (Figure 1, Key Figure), but not potential pathological consequences. most findings concerning fact increases steadily conception. concept first described geneticist Wilhelm Weinberg 1912, who observed sporadic achondroplasia more common last-born children than first-born [8Weinberg W. Zur Vererbung des Zwergwuchses.Arch. Rassen Gesell. 1912; German): 710-718Google For several association stronger [9Penrose L.S. Parental mutation.Lancet. 1955; 266: 312-313Abstract (198) It hypothesized associations could unprecise copying large cell divisions required continuous sperm production males 9Penrose 10Crow J.F. origins, patterns implications spontaneous mutation.Nat. 2000; 1: 40-47Crossref (615) direct observation DNM rates higher offspring fathers advanced WGS 78 Icelandic [11Kong A. al.Rate importance father's disease risk.Nature. 488: 471-475Crossref (1191) This dependent father, slope two additional per year life time increased numbers generally called effect. main hypothesis incidental errors replications 11Kong Genome male ensure cells. stem cells spermatogonia, located seminiferous epithelium. Spermatogonia divide renew themselves give rise spermatocytes, will eventually differentiate [12Sharma S. al.Spermatogonial cells: updates specification clinical relevance.Hum. Reprod. Update. 2019; 25: 275-297Crossref (29) During aging, mean spermatogonium continues increase, replication potentially introducing due errors. Due this, spermatogonia believed accumulate explaining Next genome-wide effect, highly specific mutations. particular activating genes, affected lineages generate other lineages. As consequence, effective rate genes up four orders magnitude rate. termed selfish spermatogonial selection (Box 1). linear [13Goriely Wilkie A.O.M. Paternal selection: causes disease.Am. Hum. 90: 175-200Abstract (190) Scholar].Box 1Selfish Spermatogonial SelectionThe fitness themselves. essential lead eradication lineage, selective advantages clonal expansion; is, outgrowth process often linked precancerous lesions. Clonal expansions tissues like bone marrow [14Genovese al.Clonal hematopoiesis blood-cancer risk blood DNA sequence.N. Engl. Med. 2014; 371: 2477-2487Crossref (1541) Scholar], skin [15Martincorena I. al.High burden pervasive positive normal skin.Science. 2015; 348: 880-886Crossref (798) esophageal epithelium [16Martincorena al.Somatic mutant clones colonize esophagus age.Science. 2018; 362: 911-917Crossref (338) well others [17Yizhak K. al.RNA sequence analysis reveals macroscopic expansion across tissues.Science. 364: eaaw0726Crossref (180) testis, driven oncogenic growth factor receptors components RAS–MAPK pathway 18Maher G.J. al.Selfish dysregulating signaling aged testes.Genome Res. 28: 1779-1790Crossref (28) consequence mutated occurs testes healthy men [19Goriely al.Regulation fate decision undifferentiated GDNF.Science. 2003; 287: 1489-1493Google 20Goriely al.Activating FGFR3 HRAS reveal shared origin congenital disorders testicular tumors.Nat. 2009; 41: 1247-1252Crossref (152) 21Giannoulatou E. al.Whole-genome spermatocytic tumors provides operating germline.PLoS One. 2017; 12: e0178169Crossref (18) carrying grows continuously much general, If passed they developmental disorders. example achondroplasia, condition characterized short stature fibroblast receptor 3 (FGFR3) gene. Achondroplasia frequently expected average occurrence strongly [10Crow 22Dakouane Giudicelli M. al.Increased frequency evidence G1138A mosaicism testis biopsies.Fertil. Steril. 2008; 89: 1651-1656Abstract shown pathogenic present high-level mosaicisms patients [20Goriely Recent confirmed general [23Francioli L.C. al.Genome-wide properties humans.Nat. 47: 822-826Crossref (194) 24Rahbari al.Timing, spectra 48: 126-133Crossref (247) 25Wong W.S.W. observations mutations.Nat. Commun. 7: 10486Crossref (85) 26Goldmann J.M. al.Parent-of-origin-specific 935-939Crossref (127) 27Jónsson H. al.Parental influence 1,548 Iceland.Nature. 549: 519-522Crossref (138) 28Goldmann al.Germline oocyte regions high double-strand-break incidence.Nat. 50: 487-492Crossref (27) datasets allowed deeper characterization 2). mainly comprise cancer [24Rahbari 29Alexandrov L.B. al.Clock-like cells.Nat. 1402-1407Crossref (410) occur wide range clock-like manner (i.e., constant rate). Therefore, likely represent DNA. line replication-error hypothesis, [29Alexandrov Surprisingly, however, With advancing age, T>G substitutions fewer non-CpG C>T [27Jónsson existence differences suggests that, besides aging-associated mutations, there another type independent age. increasing balance types shifts becomes biased towards mutations.Box 2Mutational SignaturesFrom genomes it exposure mutagens failure repair pathways patterns. An light-associated cancers, CC>TT very [30Pfeifer G.P. al.Mutations induced ultraviolet light.Mutat. Mol. Mech. Mutagen. 2005; 571: 19-31Crossref (527) advent NGS systematic collections well-annotated [31Nik-Zainal al.Mutational molding breast cancers.Cell. 149: 979-993Abstract (1124) 32Alexandrov al.Signatures cancer.Nature. 500: 415-421Crossref (5077) 33Alexandrov L. repertoire cancer.bioRxiv. (Published online July 3, 2019)https://doi.org/10.1101/322859Google analyses, were analyzed differentiating six stratifying nucleotides surrounding base pair, 96 types. By mathematically deconvoluting archetypical efforts identified 49 single-nucleotide-substitution signatures. annotated mechanisms. available (https://cancer.sanger.ac.uk/cosmic/signatures). Analysis comparison hint From According genome-replication should directly proportional model estimating zygote includes following factors 34Clermont Y. cycle man.Am. Anat. 1963; 112: 35-51Crossref (464) 35Drost J.B. Lee W.R. Biological basis mutation: comparisons among Drosophila, mouse, human.Environ. 1995; 48-64Crossref (191) First, embryogenesis, about ten until specified established. Second, sex organ development, ducts colonized germ cells, requires 24 after specification. further fetal period childhood, rests no occur. Starting puberty, precursors. estimated divides 23 [36Heller C.G. Clermont Spermatogenesis man: estimate duration.Science. 140: 184-186Crossref (226) Finally, age-independent needed proceed cell. To example, 30-year-old divisions, plus 17 (assuming onset 13 [37Nielsen C.T. al.Onset release spermatozoa (spermarche) boys relation growth, pubic hair, height.J. Clin. Endocrinol. Metab. 1986; 62: 532-535Crossref (150) Scholar]), finally spermatogenesis. total 429 replications. Fathers 20 60 would 199 1119 replications, respectively. However, estimates accrual five between parental ages less three, 40 91, respectively [28Goldmann Supporting epidemiological giving birth child disorder (of fraction [38Gilissen C. al.Genome identifies major disability.Nature. 511: 344-347Crossref (677) Scholar]) only (from 0.24% mothers below 22 0.47% above 42 years) [39Deciphering Developmental Disorders StudyPrevalence architecture disorders.Nature. 542: 433-438Crossref (584) mismatch data reported remains unresolved [40Ségurel al.Determinants variation germline.Annu. Genomics 15: 47-70Crossref (148) 41Forster P. al.Elevated teenage fathers.Proc. 282: 20142898Crossref (30) 42Gao Z. al.Interpreting dependence time.PLoS 14: e1002355Crossref (46) 43Scally Mutation structure.Philos. Trans. Soc. Lond. B 20150137Crossref (20) 44Gao al.Overlooked roles damage generating mutations.Proc. Natl U. 116: 9491-9500Crossref (45) A annual post-pubertal division 1960s Heller radiolabeled showed lasts 16 days, extrapolate year. extrapolation implicitly assumes interruptions resting phases divisions. nature self-renewal unidirectional rather stochastic transitions, stages without replicative activity 45Hara al.Mouse spermatogenic continually interconvert equipotent singly isolated syncytial states.Cell Stem Cell. 658-672Abstract (163) 46Krieger T. Simons B.D. Dynamic heterogeneity.Development. 142: 1396-1406Crossref (62) Such nonhierarchical stochastic, oscillation supported single-cell ways. analyses single sp

Language: Английский

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Hardwiring Stem Cell Communication through Tissue Structure

Cell, Journal Year: 2016, Volume and Issue: 164(6), P. 1212 - 1225

Published: March 1, 2016

Language: Английский

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