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Stefano Rivella: Stress Erythropoiesis and the Role of HRG1-Mediated Heme Import
Stefano Rivella/LinkedIn
Jun 27, 2026, 13:16

Stefano Rivella: Stress Erythropoiesis and the Role of HRG1-Mediated Heme Import

Stefano Rivella, Kwame Ohene-Frempong Chair on Sickle Cell Anemia Professor of Pediatrics at The Children’s Hospital of Philadelphia Research Institute, shared on LinkedIn about a recent article he authored, published in Blood Red Cells and Iron, adding:

”Borrowed Heme: Rethinking Hemoglobinization

This editorial (commenting on Belot et al., Science 2026) discusses erythroid precursors can import heme from their microenvironment through the HRG1 transporter during stress erythropoiesis, overturning the long-held view that erythroid cells rely solely on cell-autonomous mitochondrial heme synthesis, a mechanism that elegantly resolves the paradox of how hemoglobinization continues even as maturing erythroblasts lose their organelles.

The piece highlights that HRG1 is strongly upregulated in stress erythropoiesis and in thalassemic erythroblasts, where excess heme import appears to worsen hemichrome-driven toxicity and ineffective erythropoiesis (partial, but not complete, HRG1 loss improves anemia in thalassemic mice, hinting at additional, dosage-dependent roles for HRG1 in macrophage iron recycling or erythroid signaling).

It also outlines unresolved mechanistic questions (e.g., whether HRG1 modulation directly reduces hemichrome/α-globin aggregation) and broader therapeutic speculation, lowering HRG1 as a strategy in β-thalassemia, Diamond-Blackfan anemia, or polycythemia vera, and raising it in X-linked sideroblastic anemia, ultimately framing the findings as evidence that erythropoiesis depends on metabolic cooperation between erythroid cells and their niche (notably macrophages recycling heme within erythroblastic islands), opening a new area of study into intercellular heme trafficking.”

Title: Borrowed Heme: Rethinking Hemoglobinization

Authors: Stefano Rivella

Stefano Rivella: Stress Erythropoiesis and the Role of HRG1-Mediated Heme Import

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Blood Red Cells and Iron Diamond-Blackfan Anemia Health Hematology Heme Hemostasis Hemostasis News Hemostasis Today HRG1 Medicine polycythemia vera Stefano Rivella Stress Erythropoiesis Thalassemia
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