Hidden heterogeneity and circadian-controlled cell fate inferred from single cell lineages

The early lineages of the zebrafish are indeterminate and a single cell labeled before the late blastula period will contribute progeny to a variety of tissues. Therefore, early cell lineages in the zebrafish do not establish future cell fates and early blastomeres must necessarily remain pluripotent. Eventually, after a period of random cell mixing, individual cells do become tissue restricted according to their later position within the blastoderm. The elucidation of a fate map for the zebrafish gastrula (Kimmel et al., 1990), has made it possible to study the processes by which cellular identity is conferred and maintained in the zebrafish. In this chapter, I describe single cell transplantation experiments designed to test for the irreversible restriction or ‘commitment’ of embryonic blastomeres in the zebrafish embryo. These experiments support the hypothesis that cell fate in the vertebrate embryo is determined by cell position. Work on the spadetail mutation will also be reviewed; this mutation causes a subset of mesodermal precursors to mismigrate during gastrulation thereby leading to a change in their eventual cell identity.

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Single-cell transcriptomics of the mouse gonadal soma reveals the establishment of sexual dimorphism in distinct cell lineages

10.1101/410407 ◽

2018 ◽

Cited By ~ 2

Author(s):

Isabelle Stévant ◽

Françoise Kühne ◽

Andy Greenfield ◽

Marie-Christine Chaboissier ◽

Emmanouil T. Dermitzakis ◽

...

Keyword(s):

Time Series ◽

Sex Determination ◽

Single Cell ◽

Cell Fate ◽

Somatic Cells ◽

Supporting Cells ◽

Single Population ◽

Cell Lineages ◽

Multipotent Progenitors ◽

Distinct Cell

SummarySex determination is a unique process that allows the study of multipotent progenitors and their acquisition of sex-specific fates during differentiation of the gonad into a testis or an ovary. Using time-series single-cell RNA sequencing (scRNA-seq) on ovarian Nr5a1-GFP+ somatic cells during sex determination, we identified a single population of early progenitors giving rise to both pre-granulosa cells and potential steroidogenic precursor cells. By comparing time-series scRNA-seq of XX and XY somatic cells, we demonstrate that the supporting cells emerge from the early progenitors with a non-sex-specific transcriptomic program, before pre-granulosa and Sertoli cells acquire their sex-specific identity. In XX and XY steroidogenic precursors similar transcriptomic profiles underlie the acquisition of cell fate, but with a delay in XX cells. Our data provide a novel framework, at single-cell resolution, for further interrogation of the molecular and cellular basis of mammalian sex determination.

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Faculty Opinions recommendation of T cell fate and clonality inference from single-cell transcriptomes.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726267567.793522648 ◽

2016 ◽

Author(s):

Andrew McKenzie

Keyword(s):

T Cell ◽

Single Cell ◽

Cell Fate

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Faculty Opinions recommendation of Single-Cell RNA Sequencing Analysis Reveals Sequential Cell Fate Transition during Human Spermatogenesis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733883362.793555704 ◽

2019 ◽

Author(s):

Miles Wilkinson

Keyword(s):

Single Cell ◽

Rna Sequencing ◽

Cell Fate ◽

Sequencing Analysis ◽

Single Cell Rna Sequencing ◽

Human Spermatogenesis

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redPATH: Reconstructing the Pseudo Development Time of Cell Lineages in Single-cell RNA-seq Data and Applications in Cancer

Genomics Proteomics & Bioinformatics ◽

10.1016/j.gpb.2020.06.014 ◽

2021 ◽

Author(s):

Kaikun Xie ◽

Zehua Liu ◽

Ning Chen ◽

Ting Chen

Keyword(s):

Single Cell ◽

Development Time ◽

Rna Seq ◽

Cell Lineages

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Single-Cell Transcriptome Analysis as a Promising Tool to Study Pluripotent Stem Cell Reprogramming

International Journal of Molecular Sciences ◽

10.3390/ijms22115988 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5988

Author(s):

Hyun Kyu Kim ◽

Tae Won Ha ◽

Man Ryul Lee

Keyword(s):

Stem Cells ◽

Single Cell ◽

Cell Fate ◽

Human Cell ◽

Transcriptome Analysis ◽

Single Cell Analysis ◽

Embryonic Stem ◽

Single Cell Level ◽

Cell Analysis ◽

Cell Level

Cells are the basic units of all organisms and are involved in all vital activities, such as proliferation, differentiation, senescence, and apoptosis. A human body consists of more than 30 trillion cells generated through repeated division and differentiation from a single-cell fertilized egg in a highly organized programmatic fashion. Since the recent formation of the Human Cell Atlas consortium, establishing the Human Cell Atlas at the single-cell level has been an ongoing activity with the goal of understanding the mechanisms underlying diseases and vital cellular activities at the level of the single cell. In particular, transcriptome analysis of embryonic stem cells at the single-cell level is of great importance, as these cells are responsible for determining cell fate. Here, we review single-cell analysis techniques that have been actively used in recent years, introduce the single-cell analysis studies currently in progress in pluripotent stem cells and reprogramming, and forecast future studies.

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Mechanistic models of cell-fate transitions from single-cell data

Current Opinion in Systems Biology ◽

10.1016/j.coisb.2021.04.004 ◽

2021 ◽

Author(s):

Gabriel Torregrosa ◽

Jordi Garcia-Ojalvo

Keyword(s):

Single Cell ◽

Cell Fate ◽

Mechanistic Models ◽

Cell Data

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The EGL-13 SOX Domain Transcription Factor Affects the Uterine Cell Lineages in Caenorhabditis elegans

Genetics ◽

10.1093/genetics/165.3.1623 ◽

2003 ◽

Vol 165 (3) ◽

pp. 1623-1628

Author(s):

Hediye Nese Cinar ◽

Keri L Richards ◽

Kavita S Oommen ◽

Anna P Newman

Keyword(s):

Transcription Factor ◽

Cell Division ◽

Caenorhabditis Elegans ◽

Cell Fate ◽

Cell Lineages

Abstract We isolated egl-13 mutants in which the cells of the Caenorhabditis elegans uterus initially appeared to develop normally but then underwent an extra round of cell division. The data suggest that egl-13 is required for maintenance of the cell fate.

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The order and logic of CD4 versus CD8 lineage choice and differentiation in mouse thymus

Nature Communications ◽

10.1038/s41467-020-20306-w ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Mohammad M. Karimi ◽

Ya Guo ◽

Xiaokai Cui ◽

Husayn A. Pallikonda ◽

Veronika Horková ◽

...

Keyword(s):

Gene Expression ◽

T Cell ◽

Single Cell ◽

Signal Strength ◽

Gene Activity ◽

Cytotoxic T Cell ◽

Individual Selection ◽

Cell Lineages ◽

Single Cell Rna Sequencing ◽

Tcr Signals

AbstractCD4 and CD8 mark helper and cytotoxic T cell lineages, respectively, and serve as coreceptors for MHC-restricted TCR recognition. How coreceptor expression is matched with TCR specificity is central to understanding CD4/CD8 lineage choice, but visualising coreceptor gene activity in individual selection intermediates has been technically challenging. It therefore remains unclear whether the sequence of coreceptor gene expression in selection intermediates follows a stereotypic pattern, or is responsive to signaling. Here we use single cell RNA sequencing (scRNA-seq) to classify mouse thymocyte selection intermediates by coreceptor gene expression. In the unperturbed thymus, Cd4+Cd8a- selection intermediates appear before Cd4-Cd8a+ selection intermediates, but the timing of these subsets is flexible according to the strength of TCR signals. Our data show that selection intermediates discriminate MHC class prior to the loss of coreceptor expression and suggest a model where signal strength informs the timing of coreceptor gene activity and ultimately CD4/CD8 lineage choice.

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