Bioinformatics portal

Our laboratory performs global transcriptomic profiling to understand the genetic programs of our cells. While all our published datasets are available for free download from the gene expression omnibus (GEO), we also provide interactive websites and processed biostatistical analyses for free use through this web portal. Please enjoy and feel free to share the microarray, population-based RNA-Seq, and single cell RNA-Seq profiles below. If you find something interesting, let us know!

Click here to access all our raw datasets through GEO

Internal only: CReM Project Index (password required)

Summary Sheet of the Kotton Lab’s sequencing approach/costs

To interact with our latest microarray and single cell RNA-Seq data, click on an entry below (grouped by publication in reverse chronological order):

1.Interact with the shiny apps from: Burgess CL et al.  Generation of human alveolar epithelial type I cells from pluripotent stem cells. Cell Stem Cell.2024 Apr 15. PMID: 38642558

• Figure 3 WT YAP, YAP5SA: https://crem-bu.shinyapps.io/scRNAseq_lentiviral_YAP5SA_iAT1_induction/
• Figure 6 L+DCI, YAP5SA, CKDCI: https://crem-bu.shinyapps.io/scRNAseq_iAT1_induction_methods/
• Figure 6 L+DCI Time Series: https://crem-bu.shinyapps.io/scRNAseq_iAT1_differentiation_time_series/
• Figure 7 3D vs ALI: https://crem-bu.shinyapps.io/scRNAseq_iAT1_3D_ALI_comparison/

2. Interactive data (SPRING) from: Ma L et al., Airway stem cell reconstitution by the transplantation of primary or pluripotent stem cell-derived basal cells. Cell Stem Cell, 2023. PMID: 37625411

• Figure 1: In vitro iBC culture://kleintools.hms.harvard.edu/tools/springViewer_1_6_dev.html?client_datasets/20_10_08_martin/D129_DSi
• Figure 2: Murine primary BC transplantation into syngeneic immunocompetent mouse tracheae://kleintools.hms.harvard.edu/tools/springViewer_1_6_dev.html?client_datasets/21_12_17_martin/Primary_Epi_Only
• Figure 4: Murine iBC transplantation into syngeneic immunocompetent mouse trachea ://kleintools.hms.harvard.edu/tools/springViewer_1_6_dev.html?client_datasets/22_01_05_martin_iBC/iBC_merged_Epi
• Figure 6: Murine iBC serial secondary transplantation 5^th gen recipient trachea:https://kleintools.hms.harvard.edu/tools/springViewer_1_6_dev.html?client_datasets/22_
• Figure 6: Murine iBC serial secondary transplantation 5^th gen recipient data merged with 1^st gen recipient data: https://kleintools.hms.harvard.edu/tools/springViewer_1_6_dev.html?client_datasets/22_09_16_martin_combined_with_previous/Epi_only
• Figure 7: Human primary BC and iBC transplantation into immunodeficient mouse trachea: https://kleintools.hms.harvard.edu/tools/springViewer_1_6_dev.html?client_datasets/combined_allHuman_withNGPT/combined_allHuman_withNGPT

3. Interactive data (SPRING) from: Herriges MJ et al., Durable alveolar engraftment of PSC-derived lung epithelial cells into immunocompetent mice Cell Stem Cell, 2023. PMID: 37625412

• Figure 2: Primary and ESC-derived tip-like cells: https://kleintools.hms.harvard.edu/tools/springViewer_1_6_dev.html?client_datasets/21_01_06_herriges_LPM_ESC_and_Primary/21_01_06_herriges_LPM_ESC_and_Primary
• Figure 4: 6- and 15-weeks post-transplantation of ESC-derived tip-like cells
  • Cluster labels:
  • 2: AT1 and AT1-like cells
  • 4: Ciliated cells
  • 6: Basal cells
  • 7: Gastric-like cells
  • 8: Neuroendocrine cells
  • 0+: AT2 cells
  • 1+13: Secretory cells
  • 3+14: AT2-like cells
  • https://kleintools.hms.harvard.edu/tools/springViewer_1_6_dev.html?client_datasets/21_01_06_herriges_with_week6_invivo/everything2
• Supp. Figure 6: 8- weeks post-transplantation of primary or ESC-derived tip-like cells
  • Cluster labels (At Res 0.5):
  • 0,7,11: Primary AT2-like cells
  • 1,2,8: AT2 cells
  • 3,12: Ciliated cells
  • 4: AT1-like cells
  • 5: ESC-derived AT2-like cells
  • 6: Secretory cells
  • 9: AT1 cells
  • 10: Basal cells
  • 13: Fibroblasts
  • 14: Gastric-like cells
  • 15: Neuroendocrine cells
  • https://kleintools.hms.harvard.edu/tools/springViewer_1_6_dev.html?client_datasets/22_08_31_michael_new/22_08_31_michael_new

4. Interactive ShinyApp (human primary/cultured AT2s and iAT2s) from: Alysandratos KD et al. Culture impact on the transcriptomic programs of primary and iPSC-derived human alveolar type 2 cells. JCI Insight. 2023 Jan 10. PMID: 36454643

5. Interactive data (SPRING plot) from Abo et al. JCI Insight 2022.  Air-liquid interface culture promotes maturation and allows environmental exposure of pluripotent stem cell–derived alveolar epithelium. SPRING from Figure 4 (scRNA-seq of SPC2 iAEC2 cells in 3D, 2D, ALI, and smoked ALI cultures).

6. Interactive data from Alysandratos et al. Cell Reports 2021. Patient-specific iPSCs carrying an SFTPC mutation reveal the intrinsic alveolar epithelial dysfunction at the inception of interstitial lung disease.:

• Interact with data from Fig. 4 (SPRING plot of day 30 and day 113 of differentiation of SFTPCI73T mutant (I73T/tdT) vs corrected (tdT/WT)  iAEC2s.
• Interact with UMAP data from Fig S3 (via our U01 IPF Consortium site).
• Interact with data from Fig S3 (SPRING plot of day 114 of differentiation SFTPCI73T mutant (clone C11) vs corrected (clone B2) iAEC2s.

7.Interactive data from Hawkins, Suzuki et al. Cell Stem Cell. 2020. Derivation of Airway Basal Stem Cells from Human Pluripotent Stem Cells:

• Interact with data from Fig 2E (SPRING plot of Media effect in 3D iPSC-ariway culture)
• Interact with data from Fig 4A (SPRING plot of BU3 NGPT iBCs after differentiation in ALI culture)
• Additional SPRING plot of scRNA-seq of BU3 NGPT ALI culture via SPRING here

8.Interactive data from Huang et al. Cell Stem Cell. Sept 2020: SARS-CoV-2 Infection of Pluripotent Stem Cell-derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response.

• Download RNA-Seq table S1 (Excel: Differentially Expressed Genes in iAT2s after SARS-CoV-2 infection).
• View the interactive ShinyApp and type in your favorite gene to see how it changes in infected iAT2s (Kotton Lab) as well as in primary adult human cultured AT2s (Tata Lab)!

9. Interactive data from Hurley et al 2020. Reconstructed Single-Cell Fate Trajectories Define Lineage Plasticity Windows during Differentiation of Human PSC-Derived Distal Lung Progenitors.

• Download primary human fetal through adult lung AEC2 RNA Seq data (week 16 gestation through adult; top 1000 most varying genes; from our paper’s figure 1; Table S1.xls)
• View the SPRING plot (from figure 3; our human iPSC distal lung directed differentiation scRNA Seq time series) — and search for your favorite gene!
• View Jun Ding’s interactive on line tool from figure 4 and follow the branching cell fate trajectories in our Continuous State Hidden Markov Model
• View the SPRING plot (from figure 7; scRNA Seq for our human iPSC-derived AEC2 that are 114 days in culture) — and search for your favorite gene!
• View the SPRING plot (from figure S5; lineage tracing of iPSC-Derived AEC2 with lentiviral barcoding and subsequent scRNA-seq ) — and search for your favorite gene!

10. Interactive data from Ikonomou et al. Nature Communications. Jan 2020: The in vivo genetic program of Primordial Lung Progenitors (E9.0 mouse):

• Download RNA seq, pairwise comparisons (28MB excel file; Table S1) from figure 3 of lung, thyroid, forebrain and their endodermal/ectodermal precursors in vivo.
• Download RNA seq comparisons of in vitro mESC-derived day 14 progenitors from figure 5h (6MB excel file: Figure 5h).

11. Query your favorite gene in the scRNA-Seq datasets for our human iPSC-derived bronchospheres and alveolospheres, published in McCauley et al Stem Cell Reports, April 2018. Single cell Transcriptomic Profiling of Pluripotent Stem Cell-Derived SCGB3A2+ Airway epithelium.

• Figure 3 interactive data: Time series Microarray of RUES2 SCGB3A2 Cherry picker ESC line: proximal differentiation through day 36 (analysis via LGEA)
• Figure 5 interactive data: scRNA seq (Fluidigm C1), RUES2 SCGB3A2 Cherry Picker ESC line. Day 27 proximal differentiation (analysis via LGEA).
• Figure 6 interactive data: scRNA-seq of day 41 proximal vs distal media (BU3 NGST line; analysis via LGEA).
• Loupe viewing instructions. Download loupe file (43MB), or access the raw data via GEO:GSE103920 (10x Chromium and Fluidigm data) or GSE103517 (Affymetrix microarray), 

12. Access our RNA-Seq data from our time series including iAEC2s, published by Jacob et al in Cell Stem Cell 2017

13. Download an excel file (42MB) with human iPSC time-series biostatistics from our Microarray profiling of major stages of the lung directed differentiation protocol (published in Hawkins et al. JCI 2017.)

14. Interact with our human iPSC-derived lung single cell RNA-Seq analyses through either:

A: The Cincinnati LGEA (Lung Gene Expression Analysis) web portal or…

B: Ian Driver’s interactive Monocle tool to look up your favorite gene in our published Monocle analysis of iPSC-derived NKX2-1+ lung progenitors (Hawkins JCI 2017; BE SURE TO TYPE YOUR GENE NAME IN CAPS ONLY).

Other analyses from our published papers:

1. Mouse ESC-derived Nkx2-1+ sorted lung vs thyroid progenitors (Download 1MB Affy array excel file from figure 4 of Serra/Kotton. Development 2017)
2. hiPSC/ESC hepatic directed differentiation time series analyses (Affy arrays): as published in Wilson/Kotton Stem Cell Reports 2015. Download an an excel file of the time series computational analysis (33MB). Or access the GEO raw data.
3. Mouse ESC/iPSC definitive endoderm directed differentiation (Christodoulou, JCI 2011)
4. Mouse in vivo fetal developing definitive endoderm
5. Human clone to clone hiPSC variability: impact on blood differentiation efficiency
6. Mouse ESC derived Nkx2-1GFP mixed lung/thyroid cells (Longmire/Kotton Cell Stem Cell 2012).