Dynamic activity of <i>Erg</i> promotes maturation of the hematopoietic system
Hematopoiesis changes over the lifetime to adapt to the physiology of development, maturation, and aging. Temporal changes in hematopoiesis parallel age-dependent incidences of certain blood diseases. Several heterochronic regulators of hematopoiesis have been identified, but how the master transcription factor (TF) circuitry of definitive hematopoietic stem cells (HSCs) adapts to changes in physiology over the life span remains unknown. In this study, we show that programmed upregulation of expression of the erythroblast transformation-specific family TF Erg from prenatal to adult maturation is evolutionarily conserved and required for implementation of adult patterns of HSC self-renewal and myeloid, erythroid, and lymphoid differentiation. Erg deficiency maintains fetal transcriptional and epigenetic programs in adulthood, and persistent juvenile phenotypes in Erg haploinsufficient mice are at least in part dependent on deregulation of the fetal-biased factor Hmga2. Overall, we identify a mechanism whereby master HSC TF networks are rewired to specify stage-specific hematopoiesis, a finding directly relevant to age-biased blood diseases.
Authors
- Mayuri Tanaka-Yano (ORCID: https://orcid.org/0000-0001-6309-3273)
- Gabriela F Rodrigues-Luiz (ORCID: https://orcid.org/0000-0003-3838-1008)
- Marcelo Falchetti (ORCID: https://orcid.org/0000-0002-9438-680X)
- Stephan George (ORCID: https://orcid.org/0000-0002-1601-0567)
- Trista E. North (ORCID: https://orcid.org/0000-0003-1249-563X)
- R. Grant Rowe (ORCID: https://orcid.org/0000-0003-3620-2950)
- Hojun Li (ORCID: https://orcid.org/0000-0002-8129-0390)
- Julia Goldstein
- Edroaldo Lummertz da Rocha (ORCID: https://orcid.org/0000-0003-0537-4223)
- Diana Chin (ORCID: https://orcid.org/0000-0002-1645-3552)
- Wade W. Sugden (ORCID: https://orcid.org/0000-0002-8907-7359)
- Berkley E. Gryder (ORCID: https://orcid.org/0000-0003-0130-2302)
- Dahai Wang (ORCID: https://orcid.org/0000-0001-5488-4831)
- Parker Côté (ORCID: https://orcid.org/0000-0001-7086-0573)
- Brianna Badalamenti
Institutions
- Boston Children's Hospital (US)
- Harvard University (US)
- University of California San Diego (US)
- Universidade Federal de Santa Catarina (BR)
- Versitech (United States) (US)
- Dana-Farber Cancer Institute (US)
- National Cancer Institute (US)
- Boston Children's Museum (US)
- Harvard Stem Cell Institute (US)
- Case Western Reserve University (US)
- Massachusetts Institute of Technology (US)
Publication Details
- Journal
- Blood Advances
- Published
- 2025-11-05
- DOI
- https://doi.org/10.1182/bloodadvances.2025017705
- Primary Topic
- Zebrafish Biomedical Research Applications
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- U.S. Department of Defense
- Boston Children's Hospital
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina
- Instituto Serrapilheira
- National Institute of Diabetes and Digestive and Kidney Diseases