Single Cell Spatial Analysis Program

Analysis of Donor Pancreata Defines the Transcriptomic Signature and Microenvironment of Early Neoplastic Lesions

Eileen S. Carpenter ; Ahmed M. Elhossiny ; Padma Kadiyala; Jay Li ; Jake McGue ; Brian D. Griffith ; Yaqing Zhang  ; Jacob Edwards  ; Sarah Nelson  ; Fatima Lima ; Katelyn L. Donahue  ; Wenting Du ; Allison C. Bischoff  ; Danyah Alomari  ; Hannah R. Watkoske ; Michael Mattea ; Stephanie The ; Carlos E. Espinoza ; Meredith Barrett  ; Christopher J. Sonnenday ; Nicholas Olden ; Chin-Tung Chen ; Nicole Peterson ; Valerie Gunchick ; Vaibhav Sahai ; Arvind Rao ; Filip Bednar ; Jiaqi Shi ; Timothy L. Frankel ; Marina Pasca di Magliano

Abstract

The adult healthy human pancreas has been poorly studied given the lack of indication to obtain tissue from the pancreas in the absence of disease and rapid postmortem degradation. We obtained pancreata from brain dead donors, thus avoiding any warm ischemia time. The 30 donors were diverse in age and race and had no known pancreas disease. Histopathologic analysis of the samples revealed pancreatic intraepithelial neoplasia (PanIN) lesions……….

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Multi-omic single-cell velocity models epigenome-transcriptome interactions and improves cell fate prediction

Chen Li, Maria C Virgilio, Kathleen L Collins, Joshua D Welch

Abstract

Multi-omic single-cell datasets, in which multiple molecular modalities are profiled within the same cell, offer an opportunity to understand the temporal relationship between epigenome and transcriptome. To realize this potential, we developed MultiVelo, a differential equation model of gene expression that extends the RNA velocity framework to incorporate epigenomic data……

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Recording of cellular physiological histories along optically readable self-assembling protein chains.

Linghu C, An B, Shpokayte M, Celiker OT, Shmoel N, Zhang R, Zhang C, Park D, Park WM, Ramirez S, Boyden ES.Nat Biotechnol. 2023 Jan 2. doi: 10.1038/s41587-022-01586-7. Online ahead of print.PMID: 36593405

Abstract

Observing cellular physiological histories is key to understanding normal and disease-related processes. Here we describe expression recording islands-a fully genetically encoded approach that enables both continual digital recording of biological information within cells and subsequent high-throughput readout in fixed cells. Learn more

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SpaceX: gene co-expression network estimation for spatial transcriptomics

Acharyya S, Zhou X, Baladandayuthapani V.Bioinformatics. 2022 Nov 15;38(22):5033-5041. doi: 10.1093/bioinformatics/btac645.PMID: 36179087

Abstract

Motivation: The analysis of spatially resolved transcriptome enables the understanding of the spatial interactions between the cellular environment and transcriptional regulation. In particular, the characterization of the gene-gene co-expression at distinct spatial locations or cell types in the tissue enables delineation of spatial co-regulatory patterns as opposed to standard differential single gene analyses…….See publication for more….

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Integrated Workflow for the Label-Free Isolation and Genomic Analysis of Single Circulating Tumor Cells in Pancreatic Cancer

Rupp B, Owen S, Ball H, Smith KJ, Gunchick V, Keller ET, Sahai V, Nagrath S.
Abstract: As pancreatic cancer is the third deadliest cancer in the U.S., the ability to study genetic alterations is necessary to provide further insight into potentially targetable regions for cancer treatment. Circulating tumor cells (CTCs) represent an especially aggressive subset of cancer cells……

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Spatially aware dimension reduction for spatial transcriptomics.

Shang L, Zhou X.Nat Commun. 2022 Nov 23;13(1):7203. doi: 10.1038/s41467-022-34879-1.PMID: 36418351 Free PMC article.

Abstract

Spatial transcriptomics are a collection of genomic technologies that have enabled transcriptomic profiling on tissues with spatial localization information. Analyzing spatial transcriptomic data is computationally challenging, as the data collected from various spatial transcriptomic technologies are often noisy and display substantial spatial correlation across tissue locations. ….learn more

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July 2023

An atlas of healthy and injured cell states and niches in the human kidney.

Lake BB, Menon R, Winfree S, Hu Q, Ferreira RM, Kalhor K, Barwinska D, Otto EA, Ferkowicz M, Diep D, Plongthongkum N, Knoten A, Urata S, Mariani LH, Naik AS, Eddy S, Zhang B, Wu Y, Salamon D, Williams JC, Wang X, Balderrama KS, Hoover PJ, Murray E, Marshall JL, Noel T, Vijayan A, Hartman A, Chen F, Waikar SS, Rosas SE, Wilson FP, Palevsky PM, Kiryluk K, Sedor JR, Toto RD, Parikh CR, Kim EH, Satija R, Greka A, Macosko EZ, Kharchenko PV, Gaut JP, Hodgin JB; KPMP Consortium; Eadon MT, Dagher PC, El-Achkar TM, Zhang K, Kretzler M, Jain S.Nature. 2023 Jul;619(7970):585-594. doi: 10.1038/s41586-023-05769-3. Epub 2023 Jul 19.PMID: 37468583 Free PMC article.
Here we applied multiple single–cell and single-nucleus assays (>400,000 nuclei or cells) and spatial imaging technologies to a broad spectrum of healthy reference kidneys (45 donors) and diseased kidneys (48 patients). …Molecular signatures permi …
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July 2023

Single-cell Profiling of Prurigo Nodularis Demonstrates Immune-Stromal Crosstalk Driving Profibrotic Responses and Reversal with Nemolizumab.

Ma F, Gharaee-Kermani M, Tsoi LC, Plazyo O, Chaskar P, Harms P, Patrick MT, Xing X, Hile G, Piketty C, Lazzari A, Van Delm W, Maverakis E, Nakamura M, Modlin RL, Kahlenberg JM, Billi AC, Julia V, Krishnaswamy JK, Gudjonsson JE.J Allergy Clin Immunol. 2023 Jul 26:S0091-6749(23)00925-9. doi: 10.1016/j.jaci.2023.07.005. Online ahead of print.PMID: 37506977
OBJECTIVE: To provide a comprehensive view of the molecular pathogenesis of PN at the single–cell level to identify and outline key pathologic processes and the cell types involved. …We further aimed to determine the impact of the interleukin-31 (IL-31) rec …
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July 2023

SiftCell: A robust framework to detect and isolate cell-containing droplets from single-cell RNA sequence reads.

Xi J, Park SR, Lee JH, Kang HM.Cell Syst. 2023 Jul 19;14(7):620-628.e3. doi: 10.1016/j.cels.2023.06.002.PMID: 37473732
Single–cell RNA sequencing (scRNA-seq) massively profiles transcriptomes of individual cells encapsulated in barcoded droplets in parallel. …A typical first step to analyze scRNA-seq data is to filter out cell-free droplets and isolate cell …
 
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July 2023

Pansclerotic morphea is characterized by IFN-γ responses priming dendritic cellfibroblast crosstalk to promote fibrosis.

Xing E, Ma F, Wasikowski R, Billi AC, Gharaee-Kermani M, Fox J, Dobry C, Victory A, Sarkar M, Xing X, Plazyo O, Chen HW, Barber GC, Jacobe H, Tsou PS, Modlin RL, Varga J, Kahlenberg JM, Tsoi LC, Gudjonsson JE, Khanna D.JCI Insight. 2023 Jul 20:e171307. doi: 10.1172/jci.insight.171307. Online ahead of print.PMID: 37471168 Free article.
We aimed to characterize molecular mechanisms driving PSM and identify therapeutically targetable pathways by performing single–cell and spatial RNA-sequencing on lesional and non-lesional skin biopsies of a PSM patient 12-months apart and 6 healthy co …
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July 2023

Genetic control of the dynamic transcriptional response to immune stimuli and glucocorticoids at single-cell resolution.

Resztak JA, Wei J, Zilioli S, Sendler E, Alazizi A, Mair-Meijers HE, Wu P, Wen X, Slatcher RB, Zhou X, Luca F, Pique-Regi R.Genome Res. 2023 Jul 13. doi: 10.1101/gr.276765.122. Online ahead of print.PMID: 37442575 Free article.
Here, we used single–cell RNA-seq to study the dynamics of the transcriptional response to glucocorticoids in activated peripheral blood mononuclear cells from 96 African American children. …Using these approaches, we showed that glucocorticoids reverse the …
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June 2023

Imaging-Based Screening Identifies Modulators of the eIF3 Translation Initiation Factor Complex in Candida albicans.

Metzner K, O’Meara MJ, Halligan B, Wotring JW, Sexton JZ, O’Meara TR.Antimicrob Agents Chemother. 2023 Jul 18;67(7):e0050323. doi: 10.1128/aac.00503-23. Epub 2023 Jun 29.PMID: 37382550 Free PMC article.
In C. albicans, a key virulence factor is the ability to transition to hyphal morphology. We developed a high-throughput image analysis pipeline to distinguish between yeast and filamentous growth in C. albicans at the single cell level. …Multiple compounds …
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June 2023

Differentiation of IL-26+ TH17 intermediates into IL-17A producers via epithelial crosstalk in psoriasis.

Fries A, Saidoune F, Kuonen F, Dupanloup I, Fournier N, Guerra de Souza AC, Haniffa M, Ma F, Gudjonsson JE, Roesner L, Li Y, Werfel T, Conrad C, Gottardo R, Modlin RL, Di Domizio J, Gilliet M.Nat Commun. 2023 Jun 30;14(1):3878. doi: 10.1038/s41467-023-39484-4.PMID: 37391412 Free PMC article.
Here we identify a population of blood T(H)17 intermediates that produce high levels of IL-26 and differentiate into IL-17A-producing T(H)17 cells upon TGF-beta1 exposure. By combining single cellRNA sequencing, TCR sequencing and spatial transcriptomics we …
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June 2023

Analysis of Donor Pancreata Defines the Transcriptomic Signature and Microenvironment of Early Neoplastic Lesions.

Carpenter ES, Elhossiny AM, Kadiyala P, Li J, McGue J, Griffith BD, Zhang Y, Edwards J, Nelson S, Lima F, Donahue KL, Du W, Bischoff AC, Alomari D, Watkoske HR, Mattea M, The S, Espinoza CE, Barrett M, Sonnenday CJ, Olden N, Chen CT, Peterson N, Gunchick V, Sahai V, Rao A, Bednar F, Shi J, Frankel TL, Pasca di Magliano M.Cancer Discov. 2023 Jun 2;13(6):1324-1345. doi: 10.1158/2159-8290.CD-23-0013.PMID: 37021392 Free PMC article.
We compared healthy pancreata to pancreatic cancer and peritumoral tissue and observed distinct transcriptomic signatures in fibroblasts and, to a lesser extent, macrophages. PanIN epithelial cells from healthy pancreata were remarkably transcri …
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March 2023

Multi-omic single-cell velocity models epigenome-transcriptome interactions and improves cell fate prediction.

Li C, Virgilio MC, Collins KL, Welch JD.Nat Biotechnol. 2023 Mar;41(3):387-398. doi: 10.1038/s41587-022-01476-y. Epub 2022 Oct 13.PMID: 36229609
Multi-omic single–cell datasets, in which multiple molecular modalities are profiled within the same cell, offer an opportunity to understand the temporal relationship between epigenome and transcriptome. …Application to multi-omic single–cell …
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February 2023

Subclonal evolution and expansion of spatially distinct THY1-positive cells is associated with recurrence in glioblastoma.

Al-Holou WN, Wang H, Ravikumar V, Shankar S, Oneka M, Fehmi Z, Verhaak RG, Kim H, Pratt D, Camelo-Piragua S, Speers C, Wahl DR, Hollon T, Sagher O, Heth JA, Muraszko KM, Lawrence TS, de Carvalho AC, Mikkelsen T, Rao A, Rehemtulla A.Neoplasia. 2023 Feb;36:100872. doi: 10.1016/j.neo.2022.100872. Epub 2023 Jan 6.PMID: 36621024 Free PMC article.
These specimens were evaluated for treatment response and to identify gene expression pathways driving treatment resistance. Findings were clinically validated using spatial transcriptomics of human GBMs. RESULTS: These studies reveal in replicate cohorts, a gene ex …
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February 2023

Bone marrow mesenchymal stem cells induce metabolic plasticity in estrogen receptor-positive breast cancer.

Buschhaus JM, Rajendran S, Chen S, Wharram BL, Bevoor AS, Cutter AC, Humphries BA, Robison TH, Farfel AP, Luker GD.Mol Cancer Res. 2023 Feb 3:MCR-22-0451. doi: 10.1158/1541-7786.MCR-22-0451. Online ahead of print.PMID: 36735350
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January 2023

Two-sample test with g-modeling and its applications.

Zhai J, Jiang H.Stat Med. 2023 Jan 15;42(1):89-104. doi: 10.1002/sim.9603. Epub 2022 Nov 22.PMID: 36412978
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January 2023

SGLT2 inhibitors mitigate kidney tubular metabolic and mTORC1 perturbations in youth onset type 2 diabetes.

Schaub JA, AlAkwaa FM, McCown PJ, Naik AS, Nair V, Eddy S, Menon R, Otto EA, Demeke D, Hartman J, Fermin D, O’Connor C, Subramanian L, Bitzer M, Harned R, Ladd P, Pyle L, Pennathur S, Inoki K, Hodgin JB, Brosius FC, Nelson RG, Kretzler M, Bjornstad P.J Clin Invest. 2023 Jan 13:e164486. doi: 10.1172/JCI164486. Online ahead of print.PMID: 36637914 Free article.
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January 2023

Subclonal evolution and expansion of spatially distinct THY1-positive cells is associated with recurrence in glioblastoma.

Al-Holou WN, Wang H, Ravikumar V, Shankar S, Oneka M, Fehmi Z, Verhaak RG, Kim H, Pratt D, Camelo-Piragua S, Speers C, Wahl DR, Hollon T, Sagher O, Heth JA, Muraszko KM, Lawrence TS, de Carvalho AC, Mikkelsen T, Rao A, Rehemtulla A.Neoplasia. 2023 Feb;36:100872. doi: 10.1016/j.neo.2022.100872. Epub 2023 Jan 6.PMID: 36621024 Free PMC article.
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January 2023

Recording of cellular physiological histories along optically readable self-assembling protein chains.

Linghu C, An B, Shpokayte M, Celiker OT, Shmoel N, Zhang R, Zhang C, Park D, Park WM, Ramirez S, Boyden ES.Nat Biotechnol. 2023 Jan 2. doi: 10.1038/s41587-022-01586-7. Online ahead of print.PMID: 36593405
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January 2023

Single-cell transcriptomics reveals a mechanosensitive injury signaling pathway in early diabetic nephropathy.

Liu S, Zhao Y, Lu S, Zhang T, Lindenmeyer MT, Nair V, Gies SE, Wu G, Nelson RG, Czogalla J, Aypek H, Zielinski S, Liao Z, Schaper M, Fermin D, Cohen CD, Delic D, Krebs CF, Grahammer F, Wiech T, Kretzler M, Meyer-Schwesinger C, Bonn S, Huber TB.Genome Med. 2023 Jan 10;15(1):2. doi: 10.1186/s13073-022-01145-4.PMID: 36627643 Free PMC article.
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January 2023

WNT signaling in the tumor microenvironment promotes immunosuppression in murine pancreatic cancer.

Du W, Menjivar RE, Donahue KL, Kadiyala P, Velez-Delgado A, Brown KL, Watkoske HR, He X, Carpenter ES, Angeles CV, Zhang Y, Pasca di Magliano M.J Exp Med. 2023 Jan 2;220(1):e20220503. doi: 10.1084/jem.20220503. Epub 2022 Oct 14.PMID: 36239683 
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December 2022

Computational modeling implicates protein scaffolding in p38 regulation of Akt.

Kinnunen PC, Luker GD, Luker KE, Linderman JJ.J Theor Biol. 2022 Dec 21;555:111294. doi: 10.1016/j.jtbi.2022.111294. Epub 2022 Oct 1.PMID: 36195198
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December 2022

HIF1α lactylation enhances KIAA1199 transcription to promote angiogenesis and vasculogenic mimicry in prostate cancer.

Luo Y, Yang Z, Yu Y, Zhang P.Int J Biol Macromol. 2022 Dec 1;222(Pt B):2225-2243. doi: 10.1016/j.ijbiomac.2022.10.014. Epub 2022 Oct 6.PMID: 36209908
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December 2022

Single-cell RNA-sequencing identifies anti-cancer immune phenotypes in the early lung metastatic niche during breast cancer.

Orbach SM, Brooks MD, Zhang Y, Campit SE, Bushnell GG, Decker JT, Rebernick RJ, Chandrasekaran S, Wicha MS, Jeruss JS, Shea LD.Clin Exp Metastasis. 2022 Dec;39(6):865-881. doi: 10.1007/s10585-022-10185-4. Epub 2022 Aug 24.PMID: 36002598
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November 2022

Spatially aware dimension reduction for spatial transcriptomics.

Shang L, Zhou X.Nat Commun. 2022 Nov 23;13(1):7203. doi: 10.1038/s41467-022-34879-1.PMID: 36418351 Free PMC article.
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November 2022

The fate of early perichondrial cells in developing bones.

Matsushita Y, Chu AKY, Tsutsumi-Arai C, Orikasa S, Nagata M, Wong SY, Welch JD, Ono W, Ono N.Nat Commun. 2022 Nov 28;13(1):7319. doi: 10.1038/s41467-022-34804-6.PMID: 36443296 Free PMC article.
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September 2022

Keap1 moderates the transcription of virus induced genes through G9a-GLPand NFκB p50 recruitment.

Burns VE, Kerppola TK.Immunology. 2022 Sep;167(1):105-121. doi: 10.1111/imm.13527. Epub 2022 Jul 7.PMID: 35751391
 
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August 2022

BASS: multi-scale and multi-sample analysis enables accurate cell type clustering and spatial domain detection in spatial transcriptomic studies.

Li Z, Zhou X.
Genome Biol. 2022 Aug 4;23(1):168. doi: 10.1186/s13059-022-02734-7.

PMID: 35927760

 
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August 2022

Dissecting the Heterogeneity of Human Thoracic Aortic Aneurysms Using Single-Cell Transcriptomics.

Mizrak D, Feng H, Yang B.
Arterioscler Thromb Vasc Biol. 2022 Aug;42(8):919-930. doi: 10.1161/ATVBAHA.122.317484. Epub 2022 Jun 16.

PMID: 35708028 Review.

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July 2022

Integrated Workflow for the Label-Free Isolation and Genomic Analysis of Single Circulating Tumor Cells in Pancreatic Cancer.

Rupp B, Owen S, Ball H, Smith KJ, Gunchick V, Keller ET, Sahai V, Nagrath S.
Int J Mol Sci. 2022 Jul 16;23(14):7852. doi: 10.3390/ijms23147852.

PMID: 35887203 Free PMC article.

 
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July 2022

Spatial Transcriptomics as a Novel Approach to Redefine Electrical Stimulation Safety.

Whitsitt QA, Koo B, Celik ME, Evans BM, Weiland JD, Purcell EK.
Front Neurosci. 2022 Jul 19;16:937923. doi: 10.3389/fnins.2022.937923. eCollection 2022.

PMID: 35928007 Free PMC article.

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July 2022

Statistical analysis of spatially resolved transcriptomic data by incorporating multiomics auxiliary information

Li Y, Zhou X, Cao H.
Genetics. 2022 Jul 30;221(4):iyac095. doi: 10.1093/genetics/iyac095.

PMID: 35731210

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July 2022

Joint dimension reduction and clustering analysis of single-cell RNA-seq and spatial transcriptomics data.

Liu W, Liao X, Yang Y, Lin H, Yeong J, Zhou X, Shi X, Liu J.
Nucleic Acids Res. 2022 Jul 8;50(12):e72. doi: 10.1093/nar/gkac219.

PMID: 35349708 Free PMC article.

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September 2021

Virus Infection Induces Keap1 Binding to Cytokine Genes, Which Recruits NF-κB p50 and G9a-GLP and Represses Cytokine Transcriptition.

Burns VE, Kerppola TK.J Immunol. 2021 Sep 1;207(5):1437-1447. doi: 10.4049/jimmunol.2100355. Epub 2021 Aug 16.PMID: 34400522 Free PMC article.
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