Year: 2025
Type: article
Abstract: ABSTRACT: 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.
Source: Blood Advances
Institutions: Boston Children's Hospital, University of California San Diego, Koch Institute for Integrative Cancer Research At MIT, Massachusetts Institute of Technology, Case Western Reserve University, Universidade Federal de Santa Catarina, National Cancer Institute, Harvard University, Dana-Farber Cancer Institute
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,800
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 Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G2043752839, THERAPEUTICALLY TARGETING SUPERCLUSTERS AT GENES DRIVING CHILDHOOD SARCOMA, G4119534169, Regulating proliferation and differentiation of erythroid progenitors, G886899955, Major histocompatibility complex gene editing to prevent hematopoietic stem cell graft rejection, Mechanisms of Flow-driven Transcriptional Control of Hematopoietic Stem Cell Development by YAP
OpenAlex ID: W4415933171