Student or educator? Sign up with your school email and get 6 months of Pro free.
Cited by 168

The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.

Deciphering Cell Lineage Specification during Male Sex Determination with Single-Cell RNA Sequencing

Open access
Stévant, Isabelle, Neirijnck, Yasmine, Borel, Christelle, Escoffier, Jessica, Smith, Lee B., Antonarakis, Stylianos E., Dermitzakis, Emmanouil T., Nef, Serge·2018·Cell Reports

Published version of a preprint

Abstract

The gonad is a unique biological system for studying cell-fate decisions. However, major questions remain regarding the identity of somatic progenitor cells and the transcriptional events driving cell differentiation. Using time-series single-cell RNA sequencing on XY mouse gonads during sex determination, we identified a single population of somatic progenitor cells prior to sex determination. A subset of these progenitors differentiates into Sertoli cells, a process characterized by a highly dynamic genetic program consisting of sequential waves of gene expression. Another subset of multipotent cells maintains their progenitor state but undergoes significant transcriptional changes restricting their competence toward a steroidogenic fate required for the differentiation of fetal Leydig cells. Our findings confirm the presence of a unique multipotent progenitor population in the gonadal primordium that gives rise to both supporting and interstitial lineages. These also provide the most granular analysis of the transcriptional events occurring during testicular cell-fate commitment.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.celrep.2018.01.043

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Research works printed but not linked: 69

  1. Albrecht, 2001, Evidence that Sry is expressed in pre-Sertoli cells and Sertoli and granulosa cells have a common precursor, Dev. Biol., 240, 92, 10.1006/dbio.2001.0438 · DOI · Paper page
  2. Barsoum, 2010, Fetal Leydig cells: progenitor cell maintenance and differentiation, J. Androl., 31, 11, 10.2164/jandrol.109.008318 · DOI
  3. Barsoum, 2011, Redundant and differential roles of transcription factors Gli1 and Gli2 in the development of mouse fetal Leydig cells, Biol. Reprod., 84, 894, 10.1095/biolreprod.110.088997 · DOI
  4. Basta, 2014, Sall1 balances self-renewal and differentiation of renal progenitor cells, Development, 141, 1047, 10.1242/dev.095851 · DOI
  5. Bhandari, 2012, SRY induced TCF21 genome-wide targets and cascade of bHLH factors during Sertoli cell differentiation and male sex determination in rats, Biol. Reprod., 87, 131, 10.1095/biolreprod.112.099663 · DOI
  6. Birk, 2000, The LIM homeobox gene Lhx9 is essential for mouse gonad formation, Nature, 403, 909, 10.1038/35002622 · DOI · Paper page
  7. Blake, 2017, Mouse Genome Database (MGD)-2017: community knowledge resource for the laboratory mouse, Nucleic Acids Res., 45, D723, 10.1093/nar/gkw1040 · DOI · Paper page
  8. Bouma, 2005, Gonadal sex reversal in mutant Dax1 XY mice: a failure to upregulate Sox9 in pre-Sertoli cells, Development, 132, 3045, 10.1242/dev.01890 · doi:10.1242/dev.01890
  9. Brennan, 2003, Pdgfr-alpha mediates testis cord organization and fetal Leydig cell development in the XY gonad, Genes Dev., 17, 800, 10.1101/gad.1052503 · DOI · Paper page
  10. Clark, 2000, Desert hedgehog (Dhh) gene is required in the mouse testis for formation of adult-type Leydig cells and normal development of peritubular cells and seminiferous tubules, Biol. Reprod., 63, 1825, 10.1095/biolreprod63.6.1825 · DOI · Paper page
  11. Cuevas, 2015, Lin41/Trim71 is essential for mouse development and specifically expressed in postnatal ependymal cells of the brain, Front. Cell Dev. Biol., 3, 20, 10.3389/fcell.2015.00020 · DOI
  12. Cui, 2004, Disrupted gonadogenesis and male-to-female sex reversal in Pod1 knockout mice, Development, 131, 4095, 10.1242/dev.01266 · DOI · Paper page
  13. DeFalco, 2011, Two distinct origins for Leydig cell progenitors in the fetal testis, Dev. Biol., 352, 14, 10.1016/j.ydbio.2011.01.011 · DOI · Paper page
  14. Gauger, 2013, Mice deficient in Sfrp1 exhibit increased adiposity, dysregulated glucose metabolism, and enhanced macrophage infiltration, PLoS ONE, 8, e78320, 10.1371/journal.pone.0078320 · DOI
  15. Ge, 2006, In search of rat stem Leydig cells: identification, isolation, and lineage-specific development, Proc. Natl. Acad. Sci. USA, 103, 2719, 10.1073/pnas.0507692103 · DOI
  16. Griffith, 2009, Genital anomalies in three male siblings with Simpson-Golabi-Behmel syndrome, Am. J. Med. Genet. A., 149A, 2484, 10.1002/ajmg.a.33047 · doi:10.1002/ajmg.a.33047
  17. Gubbay, 1990, A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes, Nature, 346, 245, 10.1038/346245a0 · DOI · Paper page
  18. Habert, 2001, Origin, differentiation and regulation of fetal and adult Leydig cells, Mol. Cell. Endocrinol., 179, 47, 10.1016/S0303-7207(01)00461-0 · DOI · Paper page
  19. Hanley, 2000, SRY, SOX9, and DAX1 expression patterns during human sex determination and gonadal development, Mech. Dev., 91, 403, 10.1016/S0925-4773(99)00307-X · DOI · Paper page
  20. Hatano, 1996, Identical origin of adrenal cortex and gonad revealed by expression profiles of Ad4BP/SF-1, Genes Cells, 1, 663, 10.1046/j.1365-2443.1996.00254.x · DOI · Paper page
  21. Inoue, 2016, Isolation and characterization of fetal Leydig progenitor cells of male mice, Endocrinology, 157, 1222, 10.1210/en.2015-1773 · DOI
  22. Jameson, 2012, Temporal transcriptional profiling of somatic and germ cells reveals biased lineage priming of sexual fate in the fetal mouse gonad, PLoS Genet., 8, e1002575, 10.1371/journal.pgen.1002575 · DOI · Paper page
  23. Josso, 1977, The anti-Müllerian hormone, Birth Defects Orig. Artic. Ser., 13, 59
  24. Karl, 1998, Sertoli cells of the mouse testis originate from the coelomic epithelium, Dev. Biol., 203, 323, 10.1006/dbio.1998.9068 · DOI · Paper page
  25. Kashimada, 2010, Sry: the master switch in mammalian sex determination, Development, 137, 3921, 10.1242/dev.048983 · DOI · Paper page
  26. Katoh-Fukui, 2012, Cbx2, a polycomb group gene, is required for Sry gene expression in mice, Endocrinology, 153, 913, 10.1210/en.2011-1055 · DOI
  27. Koopman, 1990, Expression of a candidate sex-determining gene during mouse testis differentiation, Nature, 348, 450, 10.1038/348450a0 · DOI · Paper page
  28. Kuroki, 2013, Epigenetic regulation of mouse sex determination by the histone demethylase Jmjd1a, Science, 341, 1106, 10.1126/science.1239864 · DOI · Paper page
  29. Lampugnani, 1993, Endothelial cell-to-cell junctions. Structural characteristics and functional role in the regulation of vascular permeability and leukocyte extravasation, Baillieres Clin. Haematol., 6, 539, 10.1016/S0950-3536(05)80187-8 · DOI
  30. Lasala, 2011, SOX9 and SF1 are involved in cyclic AMP-mediated upregulation of anti-Mullerian gene expression in the testicular prepubertal Sertoli cell line SMAT1, Am. J. Physiol. Endocrinol. Metab., 301, E539, 10.1152/ajpendo.00187.2011 · DOI
  31. Lavery, 2012, Testicular differentiation occurs in absence of R-spondin1 and Sox9 in mouse sex reversals, PLoS Genet., 8, e1003170, 10.1371/journal.pgen.1003170 · doi:10.1371/journal.pgen.1003170
  32. Li, 2012, Foxp1/4 control epithelial cell fate during lung development and regeneration through regulation of anterior gradient 2, Development, 139, 2500, 10.1242/dev.079699 · DOI
  33. Lin, 2017, Numb regulates somatic cell lineage commitment during early gonadogenesis in mice, Development, 144, 1607
  34. Liu, 2016, Mapping lineage progression of somatic progenitor cells in the mouse fetal testis, Development, 143, 3700, 10.1242/dev.135756 · doi:10.1242/dev.135756
  35. Ludbrook, 2004, Sex determination: a ‘window’ of DAX1 activity, Trends Endocrinol. Metab., 15, 116, 10.1016/j.tem.2004.02.002 · DOI
  36. Manuylov, 2011, Conditional ablation of Gata4 and Fog2 genes in mice reveals their distinct roles in mammalian sexual differentiation, Dev. Biol., 353, 229, 10.1016/j.ydbio.2011.02.032 · DOI
  37. Matson, 2011, DMRT1 prevents female reprogramming in the postnatal mammalian testis, Nature, 476, 101, 10.1038/nature10239 · DOI · Paper page
  38. Mazaud, 2002, Lhx9 expression during gonadal morphogenesis as related to the state of cell differentiation, Gene Expr. Patterns, 2, 373, 10.1016/S1567-133X(02)00050-9 · doi:10.1016/s1567-133x(02)00050-9
  39. Meeks, 2003, Dax1 is required for testis determination, Nat. Genet., 34, 32, 10.1038/ng1141 · DOI · Paper page
  40. Migrenne, 2001, Luteinizing hormone-dependent activity and luteinizing hormone-independent differentiation of rat fetal Leydig cells, Mol. Cell. Endocrinol., 172, 193, 10.1016/S0303-7207(00)00339-7 · DOI
  41. Minkina, 2014, DMRT1 protects male gonadal cells from retinoid-dependent sexual transdifferentiation, Dev. Cell, 29, 511, 10.1016/j.devcel.2014.04.017 · DOI
  42. Miyabayashi, 2013, Aristaless related homeobox gene, Arx, is implicated in mouse fetal Leydig cell differentiation possibly through expressing in the progenitor cells, PLoS ONE, 8, e68050, 10.1371/journal.pone.0068050 · DOI
  43. Munger, 2013, Fine time course expression analysis identifies cascades of activation and repression and maps a putative regulator of mammalian sex determination, PLoS Genet., 9, e1003630, 10.1371/journal.pgen.1003630 · DOI
  44. Nasdala, 2002, A transmembrane tight junction protein selectively expressed on endothelial cells and platelets, J. Biol. Chem., 277, 16294, 10.1074/jbc.M111999200 · DOI · Paper page
  45. Nef, 2000, Hormones in male sexual development, Genes Dev., 14, 3075, 10.1101/gad.843800 · DOI · Paper page
  46. Nef, 2005, Gene expression during sex determination reveals a robust female genetic program at the onset of ovarian development, Dev. Biol., 287, 361, 10.1016/j.ydbio.2005.09.008 · DOI · Paper page
  47. Pitetti, 2013, Insulin and IGF1 receptors are essential for XX and XY gonadal differentiation and adrenal development in mice, PLoS Genet., 9, e1003160, 10.1371/journal.pgen.1003160 · DOI
  48. Pott, 2015, Single-cell ATAC-seq: strength in numbers, Genome Biol., 16, 172, 10.1186/s13059-015-0737-7 · DOI
  49. Qin, 2008, Essential roles of COUP-TFII in Leydig cell differentiation and male fertility, PLoS ONE, 3, e3285, 10.1371/journal.pone.0003285 · DOI
  50. Ramani, 2017, Massively multiplex single-cell Hi-C, Nat. Methods, 14, 263, 10.1038/nmeth.4155 · DOI · Paper page
  51. Schmahl, 2000, Sry induces cell proliferation in the mouse gonad, Development, 127, 65, 10.1242/dev.127.1.65 · doi:10.1242/dev.127.1.65
  52. Schnabel, 2003, Pbx1 is essential for adrenal development and urogenital differentiation, Genesis, 37, 123, 10.1002/gene.10235 · DOI · Paper page
  53. Sinclair, 1990, A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif, Nature, 346, 240, 10.1038/346240a0 · DOI · Paper page
  54. Stallings, 2002, Development of a transgenic green fluorescent protein lineage marker for steroidogenic factor 1, Mol. Endocrinol., 16, 2360, 10.1210/me.2002-0003 · DOI
  55. Svingen, 2013, Building the mammalian testis: origins, differentiation, and assembly of the component cell populations, Genes Dev., 27, 2409, 10.1101/gad.228080.113 · DOI · Paper page
  56. Swain, 1998, Dax1 antagonizes Sry action in mammalian sex determination, Nature, 391, 761, 10.1038/35799 · DOI · Paper page
  57. Takayama, 2008, FOXP1 is an androgen-responsive transcription factor that negatively regulates androgen receptor signaling in prostate cancer cells, Biochem. Biophys. Res. Commun., 374, 388, 10.1016/j.bbrc.2008.07.056 · DOI
  58. Tang, 2008, Notch signaling maintains Leydig progenitor cells in the mouse testis, Development, 135, 3745, 10.1242/dev.024786 · DOI
  59. van der Maaten, 2008, Visualizing data using t-SNE, J. Mach. Learn. Res., 9, 2579
  60. van Keimpema, 2015, The forkhead transcription factor FOXP1 represses human plasma cell differentiation, Blood, 126, 2098, 10.1182/blood-2015-02-626176 · DOI
  61. Warr, 2009, Sfrp1 and Sfrp2 are required for normal male sexual development in mice, Dev. Biol., 326, 273, 10.1016/j.ydbio.2008.11.023 · DOI
  62. Warr, 2012, Gadd45γ and Map3k4 interactions regulate mouse testis determination via p38 MAPK-mediated control of Sry expression, Dev. Cell, 23, 1020, 10.1016/j.devcel.2012.09.016 · DOI
  63. Wen, 2016, Development, function and fate of fetal Leydig cells, Semin. Cell Dev. Biol., 59, 89, 10.1016/j.semcdb.2016.03.003 · DOI
  64. Wilhelm, 2002, The Wilms tumor suppressor WT1 regulates early gonad development by activation of Sf1, Genes Dev., 16, 1839, 10.1101/gad.220102 · DOI · Paper page
  65. Wilhelm, 2005, Sertoli cell differentiation is induced both cell-autonomously and through prostaglandin signaling during mammalian sex determination, Dev. Biol., 287, 111, 10.1016/j.ydbio.2005.08.039 · doi:10.1016/j.ydbio.2005.08.039
  66. Yang, 2015, Lin28 promotes the proliferative capacity of neural progenitor cells in brain development, Development, 142, 1616, 10.1242/dev.120543 · DOI · Paper page
  67. Yu, 2017, BEX4 upregulation alters Sertoli cell growth properties and protein expression profiles: An explanation for cadmium-induced testicular Sertoli cell injury, J. Biochem. Mol. Toxicol., 31, e21908, 10.1002/jbt.21908 · DOI
  68. Zhang, 2015, Reprogramming of Sertoli cells to fetal-like Leydig cells by Wt1 ablation, Proc. Natl. Acad. Sci. USA, 112, 4003, 10.1073/pnas.1422371112 · DOI
  69. Zhao, 2017, SOX4 regulates gonad morphogenesis and promotes male germ cell differentiation in mice, Dev. Biol., 423, 46, 10.1016/j.ydbio.2017.01.013 · DOI

Cited by

See all 168

Metadata

Authors
Stévant, I., Neirijnck, Y., Borel, C., Escoffier, J., Smith, L. B., Antonarakis, S. E., Dermitzakis, E. T., & Nef, S.
Venue
Cell Reports
Publisher
Elsevier BV
Published
2018-02
Volume
22
Issue
6
Pages
1589-1599
ISSN
2211-1247 (ISSN-L)
OpenAlex
W2754846283
Cited by
168
References
4
FWCI
11.66
Type
journal article
Language
en
Open access
gold
Licence
Funders
  • Swiss National Science Foundation (31003A_173070, 51PHI0-141994)
  • Département de l’Instruction Publique of the State of Geneva

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.