HSPCs display within-family homogeneity in differentiation and proliferation despite population heterogeneity

  1. Tamar Tak
  2. Giulio Prevedello
  3. Gaël Simon
  4. Noémie Paillon
  5. Camélia Benlabiod
  6. Caroline Marty
  7. Isabelle Plo
  8. Ken R Duffy
  9. Leïla Perié  Is a corresponding author
  1. Institut Curie, France
  2. INSERM, Gustave Roussy, France
  3. Institut Gustave Roussy; INSERM U1170, France
  4. Maynooth University, Ireland

Abstract

High-throughput single cell methods have uncovered substantial heterogeneity in the pool of hematopoietic stem and progenitor cells (HSPCs), but how much instruction is inherited by offspring from their heterogeneous ancestors remains unanswered. Using a method that enables simultaneous determination of common ancestor, division number, and differentiation status of a large collection of single cells, our data revealed that murine cells that derived from a common ancestor had significant similarities in their division progression and differentiation outcomes. Although each family diversifies, the overall collection of cell types observed is composed of homogeneous families. Heterogeneity between families could be explained, in part, by differences in ancestral expression of cell-surface markers. Our analyses demonstrate that fate decision by cells are largely inherited from ancestor cells, indicating the importance of common ancestor effects. These results may have ramifications for bone marrow transplantation and leukemia, where substantial heterogeneity in HSPC behavior is observed.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data has been provided for Figures 1-4 in supplemental File 1.

Article and author information

Author details

  1. Tamar Tak

    UMR168 Physico-chimie, Institut Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5959-7927
  2. Giulio Prevedello

    CNRS UMR 3348, Institut Curie, Orsay, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9857-2351
  3. Gaël Simon

    UMR168 Physico-chimie, Institut Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Noémie Paillon

    UMR168 Physico-chimie, Institut Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6848-3016
  5. Camélia Benlabiod

    UMR1287, INSERM, Gustave Roussy, Villejuif, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Caroline Marty

    UMR1287, INSERM, Gustave Roussy, Villejuif, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Isabelle Plo

    INSERM U1170, Institut Gustave Roussy; INSERM U1170, VILLEJUIF, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Ken R Duffy

    Hamilton Institute, Maynooth University, Co Kildare, Ireland
    Competing interests
    The authors declare that no competing interests exist.
  9. Leïla Perié

    UMR168 Physico-chimie, Institut Curie, Paris, France
    For correspondence
    leila.perie@curie.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0798-4498

Funding

Bettencourt-Schue (ATIP-Avenir)

  • Leïla Perié

Labex CelTisPhyBio (ANR-10-LBX-0038)

  • Leïla Perié

Idex (Paris-Sciece-Lettres Program ANR-10-IDEX-0001-02 PSL)

  • Leïla Perié

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All the experimental procedures were approved by the local ethics committee (Comité d'Ethique en expérimentation animale de l'Institut Curie) under approval number DAP 2016 006.

Reviewing Editor

  1. Utpal Banerjee, University of California, Los Angeles, United States

Version history

  1. Received: July 1, 2020
  2. Accepted: May 17, 2021
  3. Accepted Manuscript published: May 18, 2021 (version 1)
  4. Version of Record published: June 3, 2021 (version 2)

Copyright

© 2021, Tak et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,431
    Page views
  • 200
    Downloads
  • 5
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Tamar Tak
  2. Giulio Prevedello
  3. Gaël Simon
  4. Noémie Paillon
  5. Camélia Benlabiod
  6. Caroline Marty
  7. Isabelle Plo
  8. Ken R Duffy
  9. Leïla Perié
(2021)
HSPCs display within-family homogeneity in differentiation and proliferation despite population heterogeneity
eLife 10:e60624.
https://doi.org/10.7554/eLife.60624

Further reading

    1. Stem Cells and Regenerative Medicine
    Lampros Mavrommatis, Hyun-Woo Jeong ... Holm Zaehres
    Research Article

    In vitro culture systems that structurally model human myogenesis and promote PAX7+ myogenic progenitor maturation have not been established. Here we report that human skeletal muscle organoids can be differentiated from induced pluripotent stem cell lines to contain paraxial mesoderm and neuromesodermal progenitors and develop into organized structures reassembling neural plate border and dermomyotome. Culture conditions instigate neural lineage arrest and promote fetal hypaxial myogenesis toward limb axial anatomical identity, with generation of sustainable uncommitted PAX7 myogenic progenitors and fibroadipogenic (PDGFRa+) progenitor populations equivalent to those from the second trimester of human gestation. Single-cell comparison to human fetal and adult myogenic progenitor /satellite cells reveals distinct molecular signatures for non-dividing myogenic progenitors in activated (CD44High/CD98+/MYOD1+) and dormant (PAX7High/FBN1High/SPRY1High) states. Our approach provides a robust 3D in vitro developmental system for investigating muscle tissue morphogenesis and homeostasis.

    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine
    Lars N Royall, Diana Machado ... Annina Denoth-Lippuner
    Research Article Updated

    During human forebrain development, neural progenitor cells (NPCs) in the ventricular zone (VZ) undergo asymmetric cell divisions to produce a self-renewed progenitor cell, maintaining the potential to go through additional rounds of cell divisions, and differentiating daughter cells, populating the developing cortex. Previous work in the embryonic rodent brain suggested that the preferential inheritance of the pre-existing (older) centrosome to the self-renewed progenitor cell is required to maintain stem cell properties, ensuring proper neurogenesis. If asymmetric segregation of centrosomes occurs in NPCs of the developing human brain, which depends on unique molecular regulators and species-specific cellular composition, remains unknown. Using a novel, recombination-induced tag exchange-based genetic tool to birthdate and track the segregation of centrosomes over multiple cell divisions in human embryonic stem cell-derived regionalised forebrain organoids, we show the preferential inheritance of the older mother centrosome towards self-renewed NPCs. Aberration of asymmetric segregation of centrosomes by genetic manipulation of the centrosomal, microtubule-associated protein Ninein alters fate decisions of NPCs and their maintenance in the VZ of human cortical organoids. Thus, the data described here use a novel genetic approach to birthdate centrosomes in human cells and identify asymmetric inheritance of centrosomes as a mechanism to maintain self-renewal properties and to ensure proper neurogenesis in human NPCs.