scholarly journals FateID infers cell fate bias in multipotent progenitors from single-cell RNA-seq data

2017 ◽  
Author(s):  
J.S. Herman ◽  
Sagar ◽  
D. Grün
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Learning Algorithm ◽  
Cell Fates ◽  
Lineage Differentiation ◽  
Multipotent Progenitors ◽  
Distinct Cell ◽  
Distinct Lineage ◽  
Cell Transcriptome

Differentiation of multipotent cells is a complex process governed by interactions of thousands of genes subject to substantial expression fluctuations. Resolving cell state heterogeneity arising during this process requires quantification of gene expression within individual cells. However, computational methods linking this heterogeneity to biases towards distinct cell fates are not well established. Here, we perform deep single-cell transcriptome sequencing of ~2,000 bone-marrow derived mouse hematopoietic progenitors enriched for lymphoid lineages. To resolve subtle transcriptome priming indicative of distinct lineage biases, we developed FateID, an iterative supervised learning algorithm for the probabilistic quantification of cell fate bias. FateID delineates domains of fate bias within progenitor populations and permits the derivation of high-resolution differentiation trajectories, revealing a common progenitor population of B cells and plasmacytoid dendritic cells, which we validated by in vitro differentiation assays. We expect that FateID will enhance our understanding of the process of cell fate choice in complex multi-lineage differentiation systems.

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

2018 ◽  
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.

Cell movements and cell fate during zebrafish gastrulation

Development ◽  
1992 ◽  
Vol 116 (Supplement) ◽  
pp. 65-73 ◽  
Author(s):  
Robert K. Ho
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Fate Map ◽  
Cell Fates ◽  
Cell Lineages ◽  
Cell Position ◽  
Vertebrate Embryo ◽  
Cellular Identity ◽  
Transplantation Experiments

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.

Molecular Mechanisms of Plant Regeneration

2019 ◽  
Vol 70 (1) ◽  
pp. 377-406 ◽  
Author(s):  
Momoko Ikeuchi ◽  
David S. Favero ◽  
Yuki Sakamoto ◽  
Akira Iwase ◽  
Duncan Coleman ◽  
...  
Keyword(s):  
Cell Fate ◽  
Molecular Mechanisms ◽  
Normal Development ◽  
Somatic Cells ◽  
Cell Fates ◽  
Developmental Programs ◽  
Hormonal Responses ◽  
Wound Stress ◽  
Directional Transport

Plants reprogram somatic cells following injury and regenerate new tissues and organs. Upon perception of inductive cues, somatic cells often dedifferentiate, proliferate, and acquire new fates to repair damaged tissues or develop new organs from wound sites. Wound stress activates transcriptional cascades to promote cell fate reprogramming and initiate new developmental programs. Wounding also modulates endogenous hormonal responses by triggering their biosynthesis and/or directional transport. Auxin and cytokinin play pivotal roles in determining cell fates in regenerating tissues and organs. Exogenous application of these plant hormones enhances regenerative responses in vitro by facilitating the activation of specific developmental programs. Many reprogramming regulators are epigenetically silenced during normal development but are activated by wound stress and/or hormonal cues.

scholarly journals Ras is required for a limited number of cell fates and not for general proliferation in Caenorhabditis elegans.

1997 ◽  
Vol 17 (5) ◽  
pp. 2716-2722 ◽  
Author(s):  
J Yochem ◽  
M Sundaram ◽  
M Han
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Cellular Proliferation ◽  
Duct Cell ◽  
Small Gtpase ◽  
Cell Fates ◽  
Larval Stages ◽  
Culture Cells ◽  
Genetic Mosaic ◽  
Distinct Cell

Experiments with mammalian tissue culture cells have implicated the small GTPase Ras in the control of cellular proliferation. Evidence is presented here that this is not the case for a living animal, the nematode Caenorhabditis elegans: proliferation late in embryogenesis and throughout the four larval stages is not noticeably affected in animals lacking Ras in various parts of their cell lineages. Instead, genetic mosaic analysis of the let-60 gene suggests that Ras is required only, at least later in development (a maternal effect cannot be excluded), for establishment of a few temporally and spatially distinct cell fates. Only one of these, the duct cell fate, appears to be essential for viability.

scholarly journals Morphogen And Community Effects Determine Cell Fates In Response To BMP4 Signaling In Human Embryonic Stem Cells

2017 ◽  
Author(s):  
Anastasiia Nemashkalo ◽  
Albert Ruzo ◽  
Idse Heemskerk ◽  
Aryeh Warmflash
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cell Fate ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Culture Conditions ◽  
Community Effects ◽  
Cell Fates ◽  
Standard Culture

AbstractParacrine signals maintain developmental states and create cell-fate patterns in vivo, and influence differentiation outcomes in human embryonic stem cells (hESCs) in vitro. Systematic investigation of morphogen signaling is hampered by the difficulty of disentangling endogenous signaling from experimentally applied ligands. Here, we grow hESCs in micropatterned colonies of 1-8 cells (“μColonies”) to quantitatively investigate paracrine signaling and the response to external stimuli. We examine BMP4-mediated differentiation in μColonies and standard culture conditions and find that in μColonies, above a threshold concentration, BMP4 gives rise to only a single cell fate, contrary to its role as a morphogen in other developmental systems. Under standard culture conditions, BMP4 acts as morphogen, but this effect requires secondary signals and particular cell densities. We further find that a “community effect” enforces a common fate within μColonies both in the state of pluripotency and when cells are differentiated, and that this effect allows more precise response to external signals. Using live cell imaging to correlate signaling histories with cell fates, we demonstrate that interactions between neighbors result in sustained, homogenous signaling necessary for differentiation.Summary StatementWe quantitatively examined signaling and differentiation in hESC colonies of varying size treated with BMP4. We show that secondary signals result in morphogen and community effects that determine cell fates.

scholarly journals Single cell transcriptome analysis reveals an essential role for Gata2b in hematopoietic lineage decisions in zebrafish

2019 ◽  
Author(s):  
Emanuele Gioacchino ◽  
Cansu Koyunlar ◽  
Hans de Looper ◽  
Madelon de Jong ◽  
Tomasz Dobrzycki ◽  
...  
Keyword(s):  
Single Cell ◽  
Transcriptome Analysis ◽  
Progenitor Cell ◽  
Adult Zebrafish ◽  
Hematopoietic Stem ◽  
Lineage Differentiation ◽  
Hematopoietic Lineage ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome ◽  
Monocytic Lineage

AbstractHematopoietic stem cells (HSCs) are tightly controlled to keep a balance between myeloid and lymphoid cell differentiation. Gata2 is a pivotal hematopoietic transcription factor required for HSC generation and maintenance. We generated a zebrafish mutant for the mammalianGata2orthologue,gata2b. We found that in adult zebrafish,gata2bis required for both neutrophilic- and monocytic lineage differentiation. Single cell transcriptome analysis revealed that the myeloid defect present in Gata2b deficient zebrafish arise in the most immature hematopoietic stem and progenitor cell (HSPC) compartment and that this population is instead committed towards the lymphoid and erythroid lineage. Taken together, we find that Gata2b is vital for the fate choice between the myeloid and lymphoid lineages.

scholarly journals Mesenchymal Stromal Cells in the Bone Marrow Niche Consist of Multi-Populations With Distinct Transcriptional and Epigenetic Properties

2021 ◽  
Author(s):  
Sanshiro Kanazawa ◽  
Hironori Hojo ◽  
Shinsuke Ohba ◽  
Junichi Iwata ◽  
Makoto Komura ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Single Cell ◽  
Expression Profiles ◽  
Marker Genes ◽  
Mouse Bone Marrow ◽  
Bone Marrow Niche ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

Abstract Although multiple studies have investigated the mesenchymal stem and progenitor cells (MSCs) that give rise to mature bone marrow, high heterogeneity in their morphologies and properties causes difficulties in molecular separation of their distinct populations. In this study, by taking advantage of the resolution of the single cell transcriptome, we analyzed Sca-1 and PDGFR-α fraction in the mouse bone marrow tissue. The single cell transcriptome enabled us to further classify the population into seven populations according to their gene expression profiles. We then separately obtained the seven populations based on candidate marker genes, and specified their gene expression properties and epigenetic landscape by ATAC-seq. Our findings will enable to elucidate the stem cell niche signal in the bone marrow microenvironment, reconstitute bone marrow in vitro, and shed light on the potentially important role of identified subpopulation in various clinical applications to the treatment of bone- and bone marrow-related diseases.

scholarly journals FateID infers cell fate bias in multipotent progenitors from single-cell RNA-seq data

2018 ◽  
Vol 15 (5) ◽  
pp. 379-386 ◽  
Author(s):  
Josip S Herman ◽  
Sagar ◽  
Dominic Grün
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Rna Seq ◽  
Multipotent Progenitors

scholarly journals Identification and characterization of distinct cell cycle stages in cardiomyocytes using the FUCCI transgenic system

2021 ◽  
Author(s):  
Marion Baniol ◽  
Francesca Murganti ◽  
Agata Smialowska ◽  
Joni Panula ◽  
Eniko Lazar ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Single Cell ◽  
Developmental Stages ◽  
Neonatal Period ◽  
Acid Oxidation ◽  
Cardiomyocyte Proliferation ◽  
Metabolic Switch ◽  
Distinct Cell ◽  
Transcriptional Changes ◽  
Cell Transcriptome

Understanding the regulatory mechanism by which cardiomyocyte proliferation transitions to endoreplication and cell cycle arrest during the neonatal period is crucial for identifying proproliferative factors and developing regenerative therapies. We used a transgenic mouse model based on the fluorescent ubiquitination-based cell cycle indicator (FUCCI) system to isolate and characterize cycling cardiomyocytes at different cell cycle stages at a single-cell resolution. Single-cell transcriptome analysis of cycling and noncycling cardiomyocytes was performed at postnatal days 0 (P0) and 7 (P7). The FUCCI system proved to be efficient for the identification of cycling cardiomyocytes with the highest mitotic activity at birth, followed by a gradual decline in the number of cycling and mitotic cardiomyocytes during the neonatal period. Cardiomyocytes showed premature cell cycle exit at G1/S shortly after birth and delayed G1/S progression during endoreplication at P7. Single-cell RNA-seq confirmed previously described signaling pathways involved in cardiomyocyte proliferation (Erbb2 and Hippo/YAP), cardiomyocyte motility, and maturation-related transcriptional changes during postnatal development, including the metabolic switch from glycolysis to fatty acid oxidation in cardiomyocytes. Additionally, we generated transcriptional profiles specific to cell division and endoreplication in cardiomyocytes. Deciphering transcriptional changes at different developmental stages and in a cell cycle-specific manner may facilitate the identification of genes important for adult cardiomyocyte proliferation and heart regeneration.

scholarly journals Lifelong single-cell profiling of cranial neural crest diversification

2021 ◽  
Author(s):  
Peter Fabian ◽  
Kuo-Chang Tseng ◽  
Mathi Thiruppathy ◽  
Claire Arata ◽  
Hung-Jhen Chen ◽  
...  
Keyword(s):  
Neural Crest ◽  
Single Cell ◽  
Cell Fate ◽  
Intrinsic Property ◽  
Chromatin Accessibility ◽  
Specific Cell ◽  
List Type ◽  
Cranial Neural Crest ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

AbstractThe cranial neural crest generates a huge diversity of derivatives, including the bulk of connective and skeletal tissues of the vertebrate head. How neural crest cells acquire such extraordinary lineage potential remains unresolved. By integrating single-cell transcriptome and chromatin accessibility profiles of cranial neural crest-derived cells across the zebrafish lifetime, we observe region-specific establishment of enhancer accessibility for distinct fates. Neural crest-derived cells rapidly diversify into specialized progenitors, including multipotent skeletal progenitors, stromal cells with a regenerative signature, fibroblasts with a unique metabolic signature linked to skeletal integrity, and gill-specific progenitors generating cell types for respiration. By retrogradely mapping the emergence of lineage-specific chromatin accessibility, we identify a wealth of candidate lineage-priming factors, including a Gata3 regulatory circuit for respiratory cell fates. Rather than multilineage potential being an intrinsic property of cranial neural crest, our findings support progressive and region-specific chromatin remodeling underlying acquisition of diverse neural crest lineage potential.HighlightsSingle-cell transcriptome and chromatin atlas of cranial neural crestProgressive emergence of region-specific cell fate competencyChromatin accessibility mapping identifies candidate lineage regulatorsGata3 function linked to gill-specific respiratory programGraphical Abstract

Sign in / Sign up

Export Citation Format

Share Document