Id1 and Id3 Maintain Steady-State Hematopoiesis by Promoting Sinusoidal Endothelial Cell Survival and Regeneration

Gadomski, Stephen; Singh, Satyendra Kumar; Singh, Shweta; Sarkar, Tanmoy; Klarmann, Kimberly D.; Berenschot, Maximillian; Seaman, Steven; Jakubison, Brad; Gudmundsson, Kristbjorn O.; Lockett, Stephen; Keller, Jonathan R.

doi:10.1016/j.celrep.2020.107572

Cited by 20 publications

(22 citation statements)

References 50 publications

(76 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…EC-specific deletion of VEGFR2 results in reduction and disorganization of blood vessels in the metaphyseal region closed to the growth plate. (75) VEGFA exists in multiple isoforms-VEGF 120 , VEGF 164 , and VEGF 188 in mouse and VEGF 121 , VEGF 145 , VEGF 165 , VEGF 183 , VEGF 186 , VEGF 189 , and VEGF 206 in human, which elicit diverse biological processes. (76,77) Nevertheless, reduced endochondral angiogenesis and mineralization occurs in mice expressing only VEGF 120 isoform.…”

Section: Role Of Vegfa During Bone Developmentmentioning

confidence: 99%

“…A recent study shows that endothelial Id1 and Id3 genes are required for the survival of bone marrow sinusoidal ECs to maintain HSC development and function during both homeostasis and acute stress such as irradiation. ( 186 ) Further, deletion of E‐selectin during irradiation, which is mainly expressed by bone marrow ECs, promotes HSC quiescence and self‐renewal. ( 187 ) Moreover, type H vessels expand after irradiation, which can regulate the regenerative angiogenesis through blood flow–mediated secretion of PDGF‐B.…”

Section: Irradiationmentioning

confidence: 99%

See 1 more Smart Citation

Bone Vasculature and Bone Marrow Vascular Niches in Health and Disease

Chen

Hendriks

Chatzis

et al. 2020

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Bone vasculature and bone marrow vascular niches supply oxygen, nutrients, and secrete angiocrine factors required for the survival, maintenance, and self-renewal of stem and progenitor cells. In the skeletal system, vasculature creates nurturing niches for bone and blood-forming stem cells. Blood vessels regulate hematopoiesis and drive bone formation during development, repair, and regeneration. Dysfunctional vascular niches induce skeletal aging, bone diseases, and hematological disorders. Recent cellular and molecular characterization of the bone marrow microenvironment has provided unprecedented insights into the complexity, heterogeneity, and functions of the bone vasculature and vascular niches. The bone vasculature is composed of distinct vessel subtypes that differentially regulate osteogenesis, hematopoiesis, and disease conditions in bones. Further, bone marrow vascular niches supporting stem cells are often complex microenvironments involving multiple different cell populations and vessel subtypes. This review provides an overview of the emerging vascular cell heterogeneity in bone and the new roles of the bone vasculature and associated vascular niches in health and disease.

show abstract

Section: Role Of Vegfa During Bone Developmentmentioning

confidence: 99%

Section: Irradiationmentioning

confidence: 99%

Bone Vasculature and Bone Marrow Vascular Niches in Health and Disease

Chen

Hendriks

Chatzis

et al. 2020

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

show abstract

“…In addition, inhibition of USP1 has the potential to target a variety of cancers (Sacco et al, 2010;Chen et al, 2011;Ma et al, 2019). According to recent studies, USP1 contributes to deubiquitination and stabilization of the differentiation inhibitory proteins of the DNA binding inhibitor (ID) family, and ID1 is known to be associated with permeability (Zhang et al, 2015;Lee et al, 2016;Gadomski et al, 2020). As the expression of ID1 regulates E-cadherin expression (Li et al, 2007), USP1 is likely to contribute the stabilization of adherens junction protein via ID1 in endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Primaquine Diphosphate, a Known Antimalarial Drug, Blocks Vascular Leakage Acting Through Junction Stabilization

Noh

Zhang²,

Kim

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Endothelial barrier integrity is important for vascular homeostasis, and hyperpermeability participates in the progression of many pathological states, such as diabetic retinopathy, ischemic stroke, chronic bowel disease, and inflammatory disease. Here, using drug repositioning, we discovered that primaquine diphosphate (PD), previously known as an antimalarial drug, was a potential blocker of vascular leakage. PD inhibited the linear pattern of vascular endothelial growth factors (VEGF)-induced disruption at the cell boundaries, blocked the formation of VEGF-induced actin stress fibers, and stabilized the cortactin actin rings in endothelial cells. PD significantly reduced leakage in the Miles assay and mouse model of streptozotocin (STZ)-induced diabetic retinopathy. Targeted prediction programs and deubiquitinating enzyme activity assays identified a potential mechanism of action for PD and demonstrated that this operates via ubiquitin specific protease 1 (USP1). USP1 inhibition demonstrated a conserved barrier function by inhibiting VEGF-induced leakage in endothelial permeability assays. Taken together, these findings suggest that PD could be used as a novel drug for vascular leakage by maintaining endothelial integrity.

show abstract

“…The mechanisms that drive hematopoietic recovery following EC/EV transplantation are not fully established, although injury-mitigation likely acts through endothelial delivery of HSC-supportive factors, including PTN, EGF, and NOTCH ligands [49,66,69,70,91,92]. In addition, evidence from Doan et al demonstrates that inhibition of BM EC apoptosis in Tie2 cre ; Bak1 −/− ; Bax fl/− mice promotes overall survival in response to lethal irradiation [93], while Type H transitional and Type L capillary sinusoids are dependent on Id1/Id3 expression for survival and proliferation following sublethal irradiation [94]. Therefore, stabilizing BM sinusoidal endothelium prior to myeloablation may be useful in protecting the vascular niche from cytotoxic insult.…”

Section: Bm Vascular Regenerationmentioning

confidence: 99%

Vascular Regulation of Hematopoietic Stem Cell Homeostasis, Regeneration, and Aging

2021

View full text Add to dashboard Cite

Purpose of Review Hematopoietic stem cells (HSCs) sit at the top of the hierarchy that meets the daily burden of blood production. HSC maintenance relies on extrinsic cues from the bone marrow (BM) microenvironment to balance stem cell self-renewal and cell fate decisions. In this brief review, we will highlight the studies and model systems that define the centralized role of BM vascular endothelium in modulating HSC activity in health and stress. Recent Findings The BM microenvironment is composed of a diverse array of intimately associated vascular and perivascular cell types. Recent dynamic imaging studies, coupled with single-cell RNA sequencing (scRNA-seq) and functional readouts, have advanced our understanding of the HSC-supportive cell types and their cooperative mechanisms that govern stem cell fate during homeostasis, regeneration, and aging. These findings have established complex and discrete vascular microenvironments within the BM that express overlapping and unique paracrine signals that modulate HSC fate. Summary Understanding the spatial and reciprocal HSC-niche interactions and the molecular mechanisms that govern HSC activity in the BM vascular microenvironment will be integral in developing therapies aimed at ameliorating hematological disease and supporting healthy hematopoietic output.

show abstract

Id1 and Id3 Maintain Steady-State Hematopoiesis by Promoting Sinusoidal Endothelial Cell Survival and Regeneration

Cited by 20 publications

References 50 publications

Bone Vasculature and Bone Marrow Vascular Niches in Health and Disease

Bone Vasculature and Bone Marrow Vascular Niches in Health and Disease

Primaquine Diphosphate, a Known Antimalarial Drug, Blocks Vascular Leakage Acting Through Junction Stabilization

Vascular Regulation of Hematopoietic Stem Cell Homeostasis, Regeneration, and Aging

Contact Info

Product

Resources

About