Tropomyosin 1 deficiency facilitates cell state transitions and enhances hemogenic endothelial cell specification during hematopoiesis
Tropomyosins coat actin filaments to impact actin-related signaling and cell morphogenesis. Genome-wide association studies have linked Tropomyosin 1 (TPM1) with human blood trait variation. TPM1 has been shown to regulate blood cell formation in vitro, but it remains unclear how or when TPM1 affects hematopoiesis. Using gene-edited induced pluripotent stem cell (iPSC) model systems, we found that TPM1 knockout augmented developmental cell state transitions and key signaling pathways, including tumor necrosis factor alpha (TNF-α) signaling, to promote hemogenic endothelial (HE) cell specification and hematopoietic progenitor cell (HPC) production. Single-cell analyses revealed decreased TPM1 expression during human HE specification, suggesting that TPM1 regulated in vivo hematopoiesis via similar mechanisms. Analyses of a TPM1 gene trap mouse model showed that TPM1 deficiency enhanced HE formation during embryogenesis, without increasing the number of hematopoietic stem cells. These findings illuminate novel effects of TPM1 on developmental hematopoiesis.
Authors
- Deborah L. French (ORCID: https://orcid.org/0000-0002-7535-1716)
- Joanna Tober (ORCID: https://orcid.org/0000-0002-4433-5879)
- Madison B Wilken (ORCID: https://orcid.org/0009-0006-8653-2658)
- Giulia Pavani (ORCID: https://orcid.org/0000-0002-2522-2684)
- James Garifallou (ORCID: https://orcid.org/0000-0002-2042-819X)
- Catriana C. Nations (ORCID: https://orcid.org/0000-0002-2709-003X)
- Nancy A. Speck (ORCID: https://orcid.org/0000-0002-1893-582X)
- Paul Gadue (ORCID: https://orcid.org/0000-0003-4344-048X)
- Laura Bennett (ORCID: https://orcid.org/0000-0002-4046-0736)
- Christopher S. Thom (ORCID: https://orcid.org/0000-0003-1830-9922)
- Gennadiy Fonar (ORCID: https://orcid.org/0000-0002-7566-5563)
- Jean Ann Maguire
- Alyssa Gagne (ORCID: https://orcid.org/0000-0002-5636-4618)
- Victor Tsao
- Stella T. Chou (ORCID: https://orcid.org/0000-0003-4333-6965)
- Nkemdilim Okoli
- Chayanne Petit
- Rong Qiu (ORCID: https://orcid.org/0009-0003-7516-7876)
Institutions
- Children's Hospital of Philadelphia (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Stem Cell Reports
- Published
- 2024-08-29
- DOI
- https://doi.org/10.1016/j.stemcr.2024.08.001
- Citations
- 6
- Primary Topic
- Zebrafish Biomedical Research Applications
- Type
- article
- Field-Weighted Citation Impact
- 1.96
Funders
- Children's Hospital of Philadelphia
- National Institutes of Health
- National Heart, Lung, and Blood Institute