In vitro models to study the direct and indirect effects of HIV-1 infection of the human brain

Brain mural cells, including pericytes and vascular smooth muscle cells, are important for vascular development, blood-brain barrier function, and neurovascular coupling, but the molecular characteristics of human brain mural cells are incompletely characterized. Single cell RNA-sequencing (scRNA-seq) is increasingly being applied to assess cellular diversity in the human brain, but the scarcity of mural cells in whole brain samples has limited their molecular profiling. Here, we leverage the combined power of multiple independent human brain scRNA-seq datasets to build a transcriptomic database of human brain mural cells. We use this combined dataset to determine human-mouse species differences in mural cell transcriptomes, culture-induced dedifferentiation of human brain pericytes, and human mural cell organotypicity, with several key findings validated by RNA fluorescence in situ hybridization. Together, this work improves knowledge regarding the molecular constituents of human brain mural cells, serves as a resource for hypothesis generation in understanding brain mural cell function, and will facilitate comparative evaluation of animal and in vitro models.

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Direct and Indirect Effects of Cannabinoids on in vitro GABA Release in the Rat Arcuate Nucleus

Journal of Neuroendocrinology ◽

10.1111/j.1365-2826.2010.01990.x ◽

2010 ◽

Vol 22 (6) ◽

pp. 585-592 ◽

Cited By ~ 7

Author(s):

J. R. W. Menzies ◽

M. Ludwig ◽

G. Leng

Keyword(s):

Indirect Effects ◽

Arcuate Nucleus ◽

Gaba Release ◽

Direct And Indirect Effects

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Direct and Indirect Effects of Androgens on Survival of Hematopoietic Progenitor Cells In Vitro

Journal of Korean Medical Science ◽

10.3346/jkms.2005.20.3.409 ◽

2005 ◽

Vol 20 (3) ◽

pp. 409 ◽

Cited By ~ 23

Author(s):

Seong-Woo Kim ◽

Jin-Hee Hwang ◽

Jae-Min Cheon ◽

Nam-Sook Park ◽

Sang-Eun Park ◽

...

Keyword(s):

Progenitor Cells ◽

Indirect Effects ◽

Hematopoietic Progenitor Cells ◽

Direct And Indirect Effects ◽

Hematopoietic Progenitor

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DIRECT AND INDIRECT EFFECTS OF X-RADIATION ON ANTIBODY-PRODUCING CELLS

Journal of Experimental Medicine ◽

10.1084/jem.105.5.417 ◽

1957 ◽

Vol 105 (5) ◽

pp. 417-424 ◽

Cited By ~ 10

Author(s):

Frank J. Dixon ◽

James C. Roberts ◽

William O. Weigle

Keyword(s):

Antibody Response ◽

Indirect Effects ◽

Lymphoid Tissue ◽

Radiation Injury ◽

Inhibitory Effect ◽

Significant Inhibition ◽

Lymphoid Cells ◽

Whole Body ◽

Direct And Indirect Effects

X-radiation appears to exert its inhibitory effect on the antibody response by two mutually dependent routes: (a) direct radiation injury to the antibody-producing lymphoid tissue, and (b) indirect effects of altered homeostasis in the radiated host on antibody-producing tissues. Neither of these two effects alone produces significant inhibition of the secondary antibody response made by transferred lymphoid cells. However, 400 to 500 r administered in vitro to the transferred cells, plus 400 r whole body x-radiation of the recipient prior to transfer, completely inhibited the antibody response.

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Direct and indirect effects of leptin on preadipocyte proliferation and differentiation

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00860.2005 ◽

2006 ◽

Vol 290 (6) ◽

pp. R1557-R1564 ◽

Cited By ~ 42

Author(s):

Blair Wagoner ◽

Dorothy B. Hausman ◽

Ruth B. S. Harris

Keyword(s):

Adipose Tissue ◽

Conditioned Medium ◽

Indirect Effects ◽

Leptin Receptor ◽

Cell Number ◽

Direct And Indirect Effects ◽

Sprague Dawley ◽

Proliferation And Differentiation

Leptin has been shown to reduce body fat in vivo. Adipocytes express the leptin receptor; therefore, it is realistic to expect a direct effect of leptin on adipocyte growth and metabolism. In vitro studies examining the effect of leptin on adipocyte metabolism require supraphysiological doses of the protein to see a decrease in lipogenesis or stimulation of lipolysis, implying an indirect action of leptin. It also is possible that leptin reduces adipose mass by inhibiting preadipocyte proliferation (increase in cell number) and/or differentiation (lipid filling). Thus we determined direct and indirect effects of leptin on preadipocyte proliferation and differentiation in vitro. We tested the effect of leptin (0–500 ng/ml), serum from leptin-infused rats (0.25% by volume), and adipose tissue-conditioned medium from leptin-infused rats (0–30% by volume) on preadipocyte proliferation and differentiation in a primary culture of cells from male Sprague-Dawley rat adipose tissue. Leptin (50 ng/ml) stimulated proliferation of preadipocytes ( P < 0.05), but 250 and 500 ng leptin/ml inhibited proliferation of both preadipocyte and stromal vascular cell fractions ( P < 0.01), as measured by [3H]thymidine incorporation. Serum from leptin-infused rats inhibited proliferation of the adipose and stromal vascular fractions ( P = 0.01), but adipose tissue-conditioned medium had no effect on proliferation of either cell fraction. None of the treatments changed preadipocyte differentiation as measured by sn-glycerophosphate dehydrogenase activity. These results suggest that leptin could inhibit preadipocyte proliferation by modifying release of a factor from tissue other than adipose tissue.

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