{"id":235764,"date":"2026-04-23T06:09:58","date_gmt":"2026-04-23T11:09:58","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2026\/04\/hes1-regulates-bone-marrow-mesenchymal-stromal-cell-function-by-suppressing-nfatc2-mediated-inflammation"},"modified":"2026-04-23T06:09:58","modified_gmt":"2026-04-23T11:09:58","slug":"hes1-regulates-bone-marrow-mesenchymal-stromal-cell-function-by-suppressing-nfatc2-mediated-inflammation","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2026\/04\/hes1-regulates-bone-marrow-mesenchymal-stromal-cell-function-by-suppressing-nfatc2-mediated-inflammation","title":{"rendered":"HES1 regulates bone marrow mesenchymal stromal cell function by suppressing NFATc2-mediated inflammation"},"content":{"rendered":"

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The bone marrow microenvironment plays a central role in hematopoiesis and hematologic diseases. A new study investigates how HES1 regulates mesenchymal stromal cell function and inflammatory signaling, exploring a novel pathway that may shape hematopoietic homeostasis and disease biology.<\/p>\n

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The Notch target gene, Hairy and enhancer of split-1 (HES1), encodes a basic helix-loop-helix transcriptional repressor that influences cell proliferation and differentiation in embryogenesis. Our previous studies indicate that HES1 is required for hematopoiesis under stress conditions. However, the role of HES1 in bone marrow (BM) microenvironment remains to be elucidated. By employing a BM niche specific Hes1 knockout mouse model, here we have investigated the role of HES1 in regulating mesenchymal stromal cell (MSC) homeostasis and their hematopoiesis supportive function. We found that while HES1 is not essential in MSC in supporting steady-state hematopoiesis, Hes1fl\/fl Prx1Cre<\/i><\/i> mice are hypersensitive to lipopolysaccharide (LPS) challenge. Deletion of Hes1 in the BM reduces MSC frequency and affects MSC self-renewal and proliferation. Hes1-deficient MSC are less functional in supporting hematopoiesis both in vitro<\/i> and ex vivo<\/i>. Transcriptome analysis reveals that disruption of Hes1 in the BM stroma alters the expression of genes critical for cellular metabolism and inflammation. Pharmacological blockage of inflammation rescues Hes1-KO MSC phenotype and improves their hematopoiesis supportive function. Mechanistically, we show that HES1 binds to the conserved E boxes in the promoter of NFATc2, a member of the AT-rich interaction domain superfamily of DNA binding protein, to suppress NFATc2-mediated inflammation. Taken together, our study unveils a pivotal role for HES1 in maintaining BM MSC hemostasis and regulating their hematopoiesis supportive function.<\/p>\n

Hematopoietic stem cells (HSC), which give rise to all blood cells, are supported by specialized microenvironments, known as niches, within bone marrow (BM) cavities.1<\/a><\/sup>,<\/sup>2<\/a><\/sup> These niches are composed of various non-hematopoietic components, including endosteal and sinusoidal endothelial cells, mesenchymal stromal cells (MSC), and osteoblast-lineage cells.3<\/a><\/sup>,<\/sup>4<\/a><\/sup> Studies have shown that BM-derived non-hematopoietic stromal cells are capable of supporting long-term hematopoiesis both in vitro<\/i> and in vivo<\/i>. Disruptions to these non-hematopoietic cells within the BM niche may negatively impact hematopoiesis. However, the precise mechanism is still poorly understood.<\/p>\n

Notch signaling, mediated by a family of highly conserved receptors, plays a critical role in maintaining bone homeostasis, partly through regulating osteoblast differentiation from MSC, whose activation is induced by their specific ligands.5<\/a><\/sup>,<\/sup>6<\/a><\/sup><\/p>\n","protected":false},"excerpt":{"rendered":"

The bone marrow microenvironment plays a central role in hematopoiesis and hematologic diseases. A new study investigates how HES1 regulates mesenchymal stromal cell function and inflammatory signaling, exploring a novel pathway that may shape hematopoietic homeostasis and disease biology. The Notch target gene, Hairy and enhancer of split-1 (HES1), encodes a basic helix-loop-helix transcriptional repressor [\u2026]<\/p>\n","protected":false},"author":662,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11],"tags":[],"class_list":["post-235764","post","type-post","status-publish","format-standard","hentry","category-biotech-medical"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/235764","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/662"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=235764"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/235764\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=235764"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=235764"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=235764"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}