Skip to content
DraconiticResearch
Search Sources API
194,161 studies31 sourcesUpdated 33 min ago
PreprintCC BY-NC-NDbioRxiv

YAP/TAZ-controlled ERK dynamics coordinate progenitor expansion and differentiation commitment

  • S. Sharma
  • H. A. Berger
  • Z. Zhang
  • T. Meyer
  • M. N. Teruel1
  1. 1Weill Cornell Medicine
Read full textPDFDOICite

Abstract

Progenitor cells must proliferate to expand the cell population, yet terminal differentiation requires this proliferative state to end. How signaling controls the duration of this proliferative window remains poorly understood. Using adipogenesis and live single-cell imaging of differentiation, cell-cycle, and ERK-activity reporters, we show that YAP and TAZ coordinate progenitor expansion with differentiation commitment by regulating ERK dynamics. YAP/TAZ maintain cells in a fluctuating high-ERK state that promotes proliferation while actively keeping the differentiation driver PPARG below the threshold for irreversible commitment. Crucially, this differentiation block is not explained by proliferation alone: inhibiting CDK4/6 or AKT suppressed proliferation without restoring differentiation, whereas MEK-ERK inhibition restored differentiation even when YAP/TAZ activity remained high. As YAP/TAZ activity decreases, dampened ERK fluctuations trigger PPARG activation. These findings support a self-limiting model in which YAP/TAZ-driven progenitor expansion progressively increases cell density and contact-dependent Hippo signaling, reducing YAP/TAZ activity and terminating the proliferative phase. Consequently, transient YAP/TAZ activation expands the progenitor pool while preserving subsequent differentiation, whereas sustained activation suppresses commitment. Together, these findings identify YAP/TAZ-controlled ERK dynamics as the nexus coordinating progenitor expansion with terminal differentiation and suggest that slower density-dependent Hippo feedback may set the duration of this proliferative window to regulate differentiated cell-number output.

Related

  1. TERT expression attenuates metabolic disorders in obese mice by promoting adipose stem and progenitor cell expansion and differentiation
    Laura Braud, Manuel Bernabe, Julien Vernerey +10
    Molecular metabolismPeer-reviewedCC BY4 citedCell biologyHAL
  2. Matrix Viscoelasticity Regulates the Stemness and Multilineage differentiation of Primary Neural Progenitor-Stem Cells in 3D
    S. Ding, J. H. Kim, M. Wang +1
    bioRxivPreprintAll rights reservedFull textNeurosciencebioRxiv
  3. Multilayered extracellular matrix derived scaffolds direct progenitor cell differentiation in vitro and osteochondral-tissue formation in vivo.
    G. Gonnella, O. Strong, V. M. Sularea +3
    bioRxivPreprintAll rights reservedFull textSystems & synthetic biologybioRxiv
  4. An Efficient Microfluidic Platform for Organ-Specific CyclicMultiaxial Loading and Differentiation of Progenitor Cells
    N. Murugesan, S. Arkat, D. Aristotle +8
    bioRxivPreprintAll rights reservedFull textSystems & synthetic biologybioRxiv
  5. Tamoxifen targets Wisp2 to impair subcutaneous adipocyte progenitor self-renewal and adipogenic differentiation
    Nisha S. Thomas, Barbara Mensah Sankofi, Haoning Howard Cen +7
    Communications BiologyPeer-reviewedCC BY-NC-ND 4.0General biologyNatureCrossref

Cite

BibTeXRIS
BibTeX
@misc{sharma2026yaptazcontrolled,
  title = {{YAP/TAZ-controlled ERK dynamics coordinate progenitor expansion and differentiation commitment}},
  author = {S. Sharma and H. A. Berger and Z. Zhang and T. Meyer and M. N. Teruel},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.24.753950},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.24.753950v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - YAP/TAZ-controlled ERK dynamics coordinate progenitor expansion and differentiation commitment
AU  - S. Sharma
AU  - H. A. Berger
AU  - Z. Zhang
AU  - T. Meyer
AU  - M. N. Teruel
PY  - 2026
DA  - 2026/09/24
PB  - bioRxiv
DO  - 10.64898/2026.09.24.753950
UR  - https://www.biorxiv.org/content/10.64898/2026.09.24.753950v1
AB  - Progenitor cells must proliferate to expand the cell population, yet terminal differentiation requires this proliferative state to end. How signaling controls the duration of this proliferative window remains poorly understood. Using adipogenesis and live single-cell imaging of differentiation, cell-cycle, and ERK-activity reporters, we show that YAP and TAZ coordinate progenitor expansion with differentiation commitment by regulating ERK dynamics. YAP/TAZ maintain cells in a fluctuating high-ERK state that promotes proliferation while actively keeping the differentiation driver PPARG below the threshold for irreversible commitment. Crucially, this differentiation block is not explained by proliferation alone: inhibiting CDK4/6 or AKT suppressed proliferation without restoring differentiation, whereas MEK-ERK inhibition restored differentiation even when YAP/TAZ activity remained high. As YAP/TAZ activity decreases, dampened ERK fluctuations trigger PPARG activation. These findings support a self-limiting model in which YAP/TAZ-driven progenitor expansion progressively increases cell density and contact-dependent Hippo signaling, reducing YAP/TAZ activity and terminating the proliferative phase. Consequently, transient YAP/TAZ activation expands the progenitor pool while preserving subsequent differentiation, whereas sustained activation suppresses commitment. Together, these findings identify YAP/TAZ-controlled ERK dynamics as the nexus coordinating progenitor expansion with terminal differentiation and suggest that slower density-dependent Hippo feedback may set the duration of this proliferative window to regulate differentiated cell-number output.
ER  -