Metabolic-scale gene activation screens identify SLCO2B1 as a heme transporter that enhances cellular iron availability

Ünlü, Gökhan; Prizer, Benjamin; Erdal, Ranya; Yeh, Hsi-Wen; Bayraktar, Erol C.; Birsoy, Kıvanç

doi:10.1016/j.molcel.2022.09.004

Cited by 3 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, it is unclear which nutrients, if any, are constraining tumor growth. As shown in this work and reported by others 62,63 , the identification of growth advantages conferred by transporter overexpression pinpoints nutrients that are functionally limiting tumor growth. Using this approach, we found that A375 melanoma cells experience glucose and amino acid limitation in xenograft tumors.…”

Section: Using Transporter Perturbations To Study Transporter Functio...supporting

confidence: 71%

A CRISPRi/a screening platform to study cellular nutrient transport in diverse microenvironments

Chidley

Darnell

Gaudio

et al. 2023

Preprint

View full text Add to dashboard Cite

Blocking the import of nutrients essential for cancer cell proliferation represents a therapeutic opportunity, but it is unclear which transporters to target. Here, we report a CRISPRi/a screening platform to systematically interrogate the contribution of specific nutrient transporters to support cancer cell proliferation in environments ranging from standard culture media to tumor models. We applied this platform to identify the transporters of amino acids in leukemia cells and found that amino acid transport is characterized by high bidirectional flux that is dependent on the composition of the microenvironment. While investigating the role of transporters in cystine starved cells, we uncovered a novel role for serotonin uptake in preventing ferroptosis. Finally, we identified transporters essential for cell proliferation in subcutaneous tumors and found that levels of glucose and amino acids can restrain proliferation in that environment. This study provides a framework for the systematic identification of critical cellular nutrient transporters, characterizing the function of such transporters, and studying how the tumor microenvironment impacts cancer metabolism.

show abstract

Section: Using Transporter Perturbations To Study Transporter Functio...supporting

confidence: 71%

A CRISPRi/a screening platform to study cellular nutrient transport in diverse microenvironments

Chidley

Darnell

Gaudio

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Interestingly, this population was exclusively identi ed in the study from Ayhan et al 32 (named as Micro2), but not in other studies. In addition to the microglia pan-markers such as APBB1IP 32 , TBXAS1 14 , LPCAT2 44 , P2RY12 45,46 , and SLCO2B1 47 , the microglia (PCDH9 high ) population also exhibits high expression of immune-related genes such as LRMDA 48 , PEAK1, SPTLC2, and CTTNBP2 49,50 (Fig. 5c), indicating a clear functional discrimination in modulating immune responses against other microglia cells.…”

Section: The Discovery Of Pcdh9 High Microglia Cells and A Comparison...mentioning

confidence: 99%

Brain Cell Atlas: An Integrative Ensemble of Cell Transcriptomes Across Human Brain Regions

Miao

Chen²,

Yin³

et al. 2023

Preprint

View full text Add to dashboard Cite

Single-cell technologies greatly accelerated our understanding of the human brain cell types and their functions. But most studies focused on only a single or a couple of brain regions in a limited number of donors. Integration of atlas-level single-cell data can offer opportunities in revealing the cell type difference among brain regions, thus rendering explanations to the functional divergence. Here we present the Brain Cell Atlas (BCA), a comprehensive reference atlas of human brain cells, by assembling single-cell data from 70 studies of the human brain throughout major developmental stages across brain regions, covering over 11.3 million cells/nuclei from both healthy and disease. Using machine-learning based algorithms, BCA provides a consensus cell type annotation, while it showcases the discovery of a rare cell population of PCDH9high microglia cells. We demonstrate the gene regulatory difference of this cell type between hippocampus and prefrontal cortex as well as the cell-cell communications related to cell functions. In short, the BCA presents an atlas-level integrative resource for comparing brain cells in different environments and conditions within the Human Cell Atlas.

show abstract

A brain cell atlas integrating single-cell transcriptomes across human brain regions

Chen,

Huang,

Huang

et al. 2024

Nat Med

View full text Add to dashboard Cite

While single-cell technologies have greatly advanced our comprehension of human brain cell types and functions, studies including large numbers of donors and multiple brain regions are needed to extend our understanding of brain cell heterogeneity. Integrating atlas-level single-cell data presents a chance to reveal rare cell types and cellular heterogeneity across brain regions. Here we present the Brain Cell Atlas, a comprehensive reference atlas of brain cells, by assembling single-cell data from 70 human and 103 mouse studies of the brain throughout major developmental stages across brain regions, covering over 26.3 million cells or nuclei from both healthy and diseased tissues. Using machine-learning based algorithms, the Brain Cell Atlas provides a consensus cell type annotation, and it showcases the identification of putative neural progenitor cells and a cell subpopulation of PCDH9high microglia in the human brain. We demonstrate the gene regulatory difference of PCDH9high microglia between hippocampus and prefrontal cortex and elucidate the cell–cell communication network. The Brain Cell Atlas presents an atlas-level integrative resource for comparing brain cells in different environments and conditions within the Human Cell Atlas.

show abstract

Metabolic-scale gene activation screens identify SLCO2B1 as a heme transporter that enhances cellular iron availability

Cited by 3 publications

References 0 publications

A CRISPRi/a screening platform to study cellular nutrient transport in diverse microenvironments

A CRISPRi/a screening platform to study cellular nutrient transport in diverse microenvironments

Brain Cell Atlas: An Integrative Ensemble of Cell Transcriptomes Across Human Brain Regions

A brain cell atlas integrating single-cell transcriptomes across human brain regions

Contact Info

Product

Resources

About