KCNJ8/ABCC9-containing K-ATP channel modulates brain vascular smooth muscle development and neurovascular coupling

Ando, Koji; Тонг, Лей; Peng, Di; Vázquez-Liébanas, Elisa; Chiyoda, Hirohisa; He, Liqun; Liu, Jianping; Kawakami, Koichi; Mochizuki, Naoki; Fukuhara, Shigetomo; Grutzendler, Jaime; Betsholtz, Christer

doi:10.1016/j.devcel.2022.04.019

Cited by 27 publications

(38 citation statements)

References 64 publications

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“…Our list of PC-preferentially expressed transcripts was consistent with previous transcriptomic analyses (Chasseigneaux et al 2018;Bondjers et al 2006); in particular, we identified Kcnj8 (encoding the ATP-sensitive inward rectifier potassium channel Kir6.1) and Abcc9 (encoding the ABC transporter 9) involved in ion transport and intercellular signaling (Nelson et al 2015). Of note, these transcripts have recently been found in brain MC progenitors and would sustain brain VSMC differentiation (Ando et al 2022). Interestingly, expression of all the PC-preferentially expressed transcripts did not differ significantly when comparing P5 and P15; this suggests that PC differentiation and maturation already complete on P5.…”

Section: Discussionsupporting

confidence: 86%

“…It would be interesting to address these pathways' role during the postnatal period. The same mechanisms might operate during the VSMC network's postnatal expansion, along with the recently described K-ATP-dependent mechanisms in postnatal VSMC differentiation (Ando et al 2022).…”

Section: Discussionmentioning

confidence: 71%

“…In particular, the exact time course of VSMCs contractile differentiation remains unclear. A recent report described MC progenitors resembling pericytes differentiating postnatally into arterial/arteriolar VSMCs (Ando et al 2022). Lastly, FBs have been shown to appear at the meningeal level around E12 while perivascular parenchymal FBs would be recruited only in the first 3 weeks after birth (Bonney et al 2022).…”

Section: Introductionmentioning

confidence: 96%

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In mice and humans, brain microvascular contractility matures postnatally

et al. 2022

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Although great efforts to characterize the embryonic phase of brain microvascular system development have been made, its postnatal maturation has barely been described. Here, we compared the molecular and functional properties of brain vascular cells on postnatal day (P)5 vs. P15, via a transcriptomic analysis of purified mouse cortical microvessels (MVs) and the identification of vascular-cell-type-specific orpreferentially expressed transcripts. We found that endothelial cells (EC), vascular smooth muscle cells (VSMC) and fibroblasts (FB) follow specific molecular maturation programs over this time period.Focusing on VSMCs, we showed that arteriolar VSMC network expands and becomes contractile resulting in a greater cerebral blood flow (CBF), with heterogenous developmental trajectories within cortical regions. Samples of human brain cortex showed the same postnatal maturation process. Thus, the postnatal phase is a critical period during which arteriolar VSMC contractility required for vessel tone and brain perfusion is acquired and mature.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 96%

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In mice and humans, brain microvascular contractility matures postnatally

et al. 2022

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“…An alternative hypothesis is that immature mural cells adopt an intermediate pericyte-VSMC phenotype and that additional factors would be required to fully achieve either fate. This hypothesis is supported by recent data demonstrating that brain VSMCs develop from a KCNJ8 + ABCC9 + mural cell progenitor, but the extent to which these common progenitors resemble mature pericytes with respect to function and global transcriptional profile remains unknown (47). We further demonstrated that N3ICD-derived mural cells isolated via FACS and replated in minimal E6 medium downregulated KCNJ8 and acquired expression of α-SMA, calponin, and SM22α, representing a potential strategy to achieve further specification of VSMCs.…”

Section: Discussionsupporting

confidence: 75%

Notch3 directs differentiation of brain mural cells from human pluripotent stem cell–derived neural crest

Gastfriend,

Snyder,

Holt

et al. 2024

Sci. Adv.

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Brain mural cells regulate development and function of the blood-brain barrier and control blood flow. Existing in vitro models of human brain mural cells have low expression of key mural cell genes, including NOTCH3 . Thus, we asked whether activation of Notch3 signaling in hPSC-derived neural crest could direct the differentiation of brain mural cells with an improved transcriptional profile. Overexpression of the Notch3 intracellular domain (N3ICD) induced expression of mural cell markers PDGFRβ, TBX2, FOXS1 , KCNJ8 , SLC6A12 , and endogenous Notch3. The resulting N3ICD-derived brain mural cells produced extracellular matrix, self-assembled with endothelial cells, and had functional K ATP channels. ChIP-seq revealed that Notch3 serves as a direct input to relatively few genes in the context of this differentiation process. Our work demonstrates that activation of Notch3 signaling is sufficient to direct the differentiation of neural crest to mural cells and establishes a developmentally relevant differentiation protocol.

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“…Zebrafish cardiac myocytes (CM) and vascular smooth muscle (VSM) cells express functional K ATP channels with similar subunit composition, structure, and metabolic sensitivity to their mammalian counterparts [ 106 ]. KCNJ8/ABCC9 containing ATP-sensitive potassium channels are involved in VSM progenitor cell differentiation in the blood vessels of the brain, which fine-tune cerebral blood flow [ 107 ]. K ATP channel modulators seem to be promising against certain types of muscle disorders such as hypokalemic periodic paralysis with vacuolar myopathies [ 108 ] or Cantú syndrome, a multiorgan condition caused by mutations in the ABCC9 and KCNJ8 genes, resulting in neuromuscular symptoms and skeletal malformations [ 109 ].…”

Section: Ion Channels Involved In Progenitor Cell Differentiationmentioning

confidence: 99%

Ca2+-Activated K+ Channels in Progenitor Cells of Musculoskeletal Tissues: A Narrative Review

Takács

Kovács

Ebeid

et al. 2023

IJMS

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Musculoskeletal disorders represent one of the main causes of disability worldwide, and their prevalence is predicted to increase in the coming decades. Stem cell therapy may be a promising option for the treatment of some of the musculoskeletal diseases. Although significant progress has been made in musculoskeletal stem cell research, osteoarthritis, the most-common musculoskeletal disorder, still lacks curative treatment. To fine-tune stem-cell-based therapy, it is necessary to focus on the underlying biological mechanisms. Ion channels and the bioelectric signals they generate control the proliferation, differentiation, and migration of musculoskeletal progenitor cells. Calcium- and voltage-activated potassium (KCa) channels are key players in cell physiology in cells of the musculoskeletal system. This review article focused on the big conductance (BK) KCa channels. The regulatory function of BK channels requires interactions with diverse sets of proteins that have different functions in tissue-resident stem cells. In this narrative review article, we discuss the main ion channels of musculoskeletal stem cells, with a focus on calcium-dependent potassium channels, especially on the large conductance BK channel. We review their expression and function in progenitor cell proliferation, differentiation, and migration and highlight gaps in current knowledge on their involvement in musculoskeletal diseases.

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KCNJ8/ABCC9-containing K-ATP channel modulates brain vascular smooth muscle development and neurovascular coupling

Cited by 27 publications

References 64 publications

In mice and humans, brain microvascular contractility matures postnatally

In mice and humans, brain microvascular contractility matures postnatally

Notch3 directs differentiation of brain mural cells from human pluripotent stem cell–derived neural crest

Ca2+-Activated K+ Channels in Progenitor Cells of Musculoskeletal Tissues: A Narrative Review

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