--- _id: '12830' abstract: - lang: eng text: Interstitial fluid (IF) accumulation between embryonic cells is thought to be important for embryo patterning and morphogenesis. Here, we identify a positive mechanical feedback loop between cell migration and IF relocalization and find that it promotes embryonic axis formation during zebrafish gastrulation. We show that anterior axial mesendoderm (prechordal plate [ppl]) cells, moving in between the yolk cell and deep cell tissue to extend the embryonic axis, compress the overlying deep cell layer, thereby causing IF to flow from the deep cell layer to the boundary between the yolk cell and the deep cell layer, directly ahead of the advancing ppl. This IF relocalization, in turn, facilitates ppl cell protrusion formation and migration by opening up the space into which the ppl moves and, thereby, the ability of the ppl to trigger IF relocalization by pushing against the overlying deep cell layer. Thus, embryonic axis formation relies on a hydraulic feedback loop between cell migration and IF relocalization. acknowledged_ssus: - _id: PreCl - _id: Bio acknowledgement: We thank Andrea Pauli (IMP) and Edouard Hannezo (ISTA) for fruitful discussions and support with the SPIM experiments; the Heisenberg group, and especially Feyza Nur Arslan and Alexandra Schauer, for discussions and feedback; Michaela Jović (ISTA) for help with the quantitative real-time PCR protocol; the bioimaging and zebrafish facilities of ISTA for continuous support; Stephan Preibisch (Janelia Research Campus) for support with the SPIM data analysis; and Nobuhiro Nakamura (Tokyo Institute of Technology) for sharing α1-Na+/K+-ATPase antibody. This work was supported by funding from the European Union (European Research Council Advanced grant 742573 to C.-P.H.), postdoctoral fellowships from EMBO (LTF-850-2017) and HFSP (LT000429/2018-L2) to D.P., and a PhD fellowship from the Studienstiftung des deutschen Volkes to F.P. article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Karla full_name: Huljev, Karla id: 44C6F6A6-F248-11E8-B48F-1D18A9856A87 last_name: Huljev - first_name: Shayan full_name: Shamipour, Shayan id: 40B34FE2-F248-11E8-B48F-1D18A9856A87 last_name: Shamipour - first_name: Diana C full_name: Nunes Pinheiro, Diana C id: 2E839F16-F248-11E8-B48F-1D18A9856A87 last_name: Nunes Pinheiro orcid: 0000-0003-4333-7503 - first_name: Friedrich full_name: Preusser, Friedrich last_name: Preusser - first_name: Irene full_name: Steccari, Irene id: 2705C766-9FE2-11EA-B224-C6773DDC885E last_name: Steccari - first_name: Christoph M full_name: Sommer, Christoph M id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87 last_name: Sommer orcid: 0000-0003-1216-9105 - first_name: Suyash full_name: Naik, Suyash id: 2C0B105C-F248-11E8-B48F-1D18A9856A87 last_name: Naik orcid: 0000-0001-8421-5508 - first_name: Carl-Philipp J full_name: Heisenberg, Carl-Philipp J id: 39427864-F248-11E8-B48F-1D18A9856A87 last_name: Heisenberg orcid: 0000-0002-0912-4566 citation: ama: Huljev K, Shamipour S, Nunes Pinheiro DC, et al. A hydraulic feedback loop between mesendoderm cell migration and interstitial fluid relocalization promotes embryonic axis formation in zebrafish. Developmental Cell. 2023;58(7):582-596.e7. doi:10.1016/j.devcel.2023.02.016 apa: Huljev, K., Shamipour, S., Nunes Pinheiro, D. C., Preusser, F., Steccari, I., Sommer, C. M., … Heisenberg, C.-P. J. (2023). A hydraulic feedback loop between mesendoderm cell migration and interstitial fluid relocalization promotes embryonic axis formation in zebrafish. Developmental Cell. Elsevier. https://doi.org/10.1016/j.devcel.2023.02.016 chicago: Huljev, Karla, Shayan Shamipour, Diana C Nunes Pinheiro, Friedrich Preusser, Irene Steccari, Christoph M Sommer, Suyash Naik, and Carl-Philipp J Heisenberg. “A Hydraulic Feedback Loop between Mesendoderm Cell Migration and Interstitial Fluid Relocalization Promotes Embryonic Axis Formation in Zebrafish.” Developmental Cell. Elsevier, 2023. https://doi.org/10.1016/j.devcel.2023.02.016. ieee: K. Huljev et al., “A hydraulic feedback loop between mesendoderm cell migration and interstitial fluid relocalization promotes embryonic axis formation in zebrafish,” Developmental Cell, vol. 58, no. 7. Elsevier, p. 582–596.e7, 2023. ista: Huljev K, Shamipour S, Nunes Pinheiro DC, Preusser F, Steccari I, Sommer CM, Naik S, Heisenberg C-PJ. 2023. A hydraulic feedback loop between mesendoderm cell migration and interstitial fluid relocalization promotes embryonic axis formation in zebrafish. Developmental Cell. 58(7), 582–596.e7. mla: Huljev, Karla, et al. “A Hydraulic Feedback Loop between Mesendoderm Cell Migration and Interstitial Fluid Relocalization Promotes Embryonic Axis Formation in Zebrafish.” Developmental Cell, vol. 58, no. 7, Elsevier, 2023, p. 582–596.e7, doi:10.1016/j.devcel.2023.02.016. short: K. Huljev, S. Shamipour, D.C. Nunes Pinheiro, F. Preusser, I. Steccari, C.M. Sommer, S. Naik, C.-P.J. Heisenberg, Developmental Cell 58 (2023) 582–596.e7. date_created: 2023-04-16T22:01:07Z date_published: 2023-04-10T00:00:00Z date_updated: 2023-08-01T14:10:38Z day: '10' ddc: - '570' department: - _id: CaHe - _id: Bio doi: 10.1016/j.devcel.2023.02.016 ec_funded: 1 external_id: isi: - '000982111800001' file: - access_level: open_access checksum: c80ca2ebc241232aacdb5aa4b4c80957 content_type: application/pdf creator: dernst date_created: 2023-04-17T07:41:25Z date_updated: 2023-04-17T07:41:25Z file_id: '12842' file_name: 2023_DevelopmentalCell_Huljev.pdf file_size: 7925886 relation: main_file success: 1 file_date_updated: 2023-04-17T07:41:25Z has_accepted_license: '1' intvolume: ' 58' isi: 1 issue: '7' language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '04' oa: 1 oa_version: Published Version page: 582-596.e7 project: - _id: 260F1432-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '742573' name: Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation - _id: 26520D1E-B435-11E9-9278-68D0E5697425 grant_number: ALTF 850-2017 name: Coordination of mesendoderm cell fate specification and internalization during zebrafish gastrulation - _id: 266BC5CE-B435-11E9-9278-68D0E5697425 grant_number: LT000429 name: Coordination of mesendoderm fate specification and internalization during zebrafish gastrulation publication: Developmental Cell publication_identifier: eissn: - 1878-1551 issn: - 1534-5807 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: A hydraulic feedback loop between mesendoderm cell migration and interstitial fluid relocalization promotes embryonic axis formation in zebrafish tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 58 year: '2023' ... --- _id: '14082' abstract: - lang: eng text: Epithelial barrier function is commonly analyzed using transepithelial electrical resistance, which measures ion flux across a monolayer, or by adding traceable macromolecules and monitoring their passage across the monolayer. Although these methods measure changes in global barrier function, they lack the sensitivity needed to detect local or transient barrier breaches, and they do not reveal the location of barrier leaks. Therefore, we previously developed a method that we named the zinc-based ultrasensitive microscopic barrier assay (ZnUMBA), which overcomes these limitations, allowing for detection of local tight junction leaks with high spatiotemporal resolution. Here, we present expanded applications for ZnUMBA. ZnUMBA can be used in Xenopus embryos to measure the dynamics of barrier restoration and actin accumulation following laser injury. ZnUMBA can also be effectively utilized in developing zebrafish embryos as well as cultured monolayers of Madin–Darby canine kidney (MDCK) II epithelial cells. ZnUMBA is a powerful and flexible method that, with minimal optimization, can be applied to multiple systems to measure dynamic changes in barrier function with spatiotemporal precision. acknowledged_ssus: - _id: PreCl - _id: Bio acknowledgement: "The authors thank their respective lab members for feedback and helpful discussions. We thank the bioimaging and zebrafish facilities of IST Austria for their support.\r\nThis work was supported by the National Institutes of Health [R01GM112794 to A.L.M.], by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science [21K06156 to T.H.], by the Grant Program for Biomedical Engineering Research from the Nakatani Foundation for Advancement of Measuring Technologies in Biomedical Engineering [to T.H.] and by funding from the European Research Council [advanced grant 742573 to C.-P.H.]. " article_number: jcs260668 article_processing_charge: No article_type: original author: - first_name: Tomohito full_name: Higashi, Tomohito last_name: Higashi - first_name: Rachel E. full_name: Stephenson, Rachel E. last_name: Stephenson - first_name: Cornelia full_name: Schwayer, Cornelia id: 3436488C-F248-11E8-B48F-1D18A9856A87 last_name: Schwayer orcid: 0000-0001-5130-2226 - first_name: Karla full_name: Huljev, Karla id: 44C6F6A6-F248-11E8-B48F-1D18A9856A87 last_name: Huljev - first_name: Atsuko Y. full_name: Higashi, Atsuko Y. last_name: Higashi - first_name: Carl-Philipp J full_name: Heisenberg, Carl-Philipp J id: 39427864-F248-11E8-B48F-1D18A9856A87 last_name: Heisenberg orcid: 0000-0002-0912-4566 - first_name: Hideki full_name: Chiba, Hideki last_name: Chiba - first_name: Ann L. full_name: Miller, Ann L. last_name: Miller citation: ama: Higashi T, Stephenson RE, Schwayer C, et al. ZnUMBA - a live imaging method to detect local barrier breaches. Journal of Cell Science. 2023;136(15). doi:10.1242/jcs.260668 apa: Higashi, T., Stephenson, R. E., Schwayer, C., Huljev, K., Higashi, A. Y., Heisenberg, C.-P. J., … Miller, A. L. (2023). ZnUMBA - a live imaging method to detect local barrier breaches. Journal of Cell Science. The Company of Biologists. https://doi.org/10.1242/jcs.260668 chicago: Higashi, Tomohito, Rachel E. Stephenson, Cornelia Schwayer, Karla Huljev, Atsuko Y. Higashi, Carl-Philipp J Heisenberg, Hideki Chiba, and Ann L. Miller. “ZnUMBA - a Live Imaging Method to Detect Local Barrier Breaches.” Journal of Cell Science. The Company of Biologists, 2023. https://doi.org/10.1242/jcs.260668. ieee: T. Higashi et al., “ZnUMBA - a live imaging method to detect local barrier breaches,” Journal of Cell Science, vol. 136, no. 15. The Company of Biologists, 2023. ista: Higashi T, Stephenson RE, Schwayer C, Huljev K, Higashi AY, Heisenberg C-PJ, Chiba H, Miller AL. 2023. ZnUMBA - a live imaging method to detect local barrier breaches. Journal of Cell Science. 136(15), jcs260668. mla: Higashi, Tomohito, et al. “ZnUMBA - a Live Imaging Method to Detect Local Barrier Breaches.” Journal of Cell Science, vol. 136, no. 15, jcs260668, The Company of Biologists, 2023, doi:10.1242/jcs.260668. short: T. Higashi, R.E. Stephenson, C. Schwayer, K. Huljev, A.Y. Higashi, C.-P.J. Heisenberg, H. Chiba, A.L. Miller, Journal of Cell Science 136 (2023). date_created: 2023-08-20T22:01:13Z date_published: 2023-08-01T00:00:00Z date_updated: 2023-12-13T12:11:18Z day: '01' ddc: - '570' department: - _id: CaHe - _id: EvBe doi: 10.1242/jcs.260668 ec_funded: 1 external_id: isi: - '001070149000001' file: - access_level: closed checksum: a399389b7e3d072f1788b63e612a10b3 content_type: application/pdf creator: dernst date_created: 2023-08-21T07:37:54Z date_updated: 2023-08-21T07:37:54Z embargo: 2024-08-10 embargo_to: open_access file_id: '14092' file_name: 2023_JourCellScience_Higashi.pdf file_size: 18665315 relation: main_file file_date_updated: 2023-08-21T07:37:54Z has_accepted_license: '1' intvolume: ' 136' isi: 1 issue: '15' language: - iso: eng month: '08' oa_version: None project: - _id: 260F1432-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '742573' name: Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation publication: Journal of Cell Science publication_identifier: eissn: - 1477-9137 issn: - 0021-9533 publication_status: published publisher: The Company of Biologists quality_controlled: '1' scopus_import: '1' status: public title: ZnUMBA - a live imaging method to detect local barrier breaches type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 136 year: '2023' ... --- _id: '9397' abstract: - lang: eng text: Accumulation of interstitial fluid (IF) between embryonic cells is a common phenomenon in vertebrate embryogenesis. Unlike other model systems, where these accumulations coalesce into a large central cavity – the blastocoel, in zebrafish, IF is more uniformly distributed between the deep cells (DC) before the onset of gastrulation. This is likely due to the presence of a large extraembryonic structure – the yolk cell (YC) at the position where the blastocoel typically forms in other model organisms. IF has long been speculated to play a role in tissue morphogenesis during embryogenesis, but direct evidence supporting such function is still sparse. Here we show that the relocalization of IF to the interface between the YC and DC/epiblast is critical for axial mesendoderm (ME) cell protrusion formation and migration along this interface, a key process in embryonic axis formation. We further demonstrate that axial ME cell migration and IF relocalization engage in a positive feedback loop, where axial ME migration triggers IF accumulation ahead of the advancing axial ME tissue by mechanically compressing the overlying epiblast cell layer. Upon compression, locally induced flow relocalizes the IF through the porous epiblast tissue resulting in an IF accumulation ahead of the leading axial ME. This IF accumulation, in turn, promotes cell protrusion formation and migration of the leading axial ME cells, thereby facilitating axial ME extension. Our findings reveal a central role of dynamic IF relocalization in orchestrating germ layer morphogenesis during gastrulation. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Karla full_name: Huljev, Karla id: 44C6F6A6-F248-11E8-B48F-1D18A9856A87 last_name: Huljev citation: ama: Huljev K. Coordinated spatiotemporal reorganization of interstitial fluid is required for axial mesendoderm migration in zebrafish gastrulation. 2021. doi:10.15479/at:ista:9397 apa: Huljev, K. (2021). Coordinated spatiotemporal reorganization of interstitial fluid is required for axial mesendoderm migration in zebrafish gastrulation. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:9397 chicago: Huljev, Karla. “Coordinated Spatiotemporal Reorganization of Interstitial Fluid Is Required for Axial Mesendoderm Migration in Zebrafish Gastrulation.” Institute of Science and Technology Austria, 2021. https://doi.org/10.15479/at:ista:9397. ieee: K. Huljev, “Coordinated spatiotemporal reorganization of interstitial fluid is required for axial mesendoderm migration in zebrafish gastrulation,” Institute of Science and Technology Austria, 2021. ista: Huljev K. 2021. Coordinated spatiotemporal reorganization of interstitial fluid is required for axial mesendoderm migration in zebrafish gastrulation. Institute of Science and Technology Austria. mla: Huljev, Karla. Coordinated Spatiotemporal Reorganization of Interstitial Fluid Is Required for Axial Mesendoderm Migration in Zebrafish Gastrulation. Institute of Science and Technology Austria, 2021, doi:10.15479/at:ista:9397. short: K. Huljev, Coordinated Spatiotemporal Reorganization of Interstitial Fluid Is Required for Axial Mesendoderm Migration in Zebrafish Gastrulation, Institute of Science and Technology Austria, 2021. date_created: 2021-05-17T12:31:30Z date_published: 2021-05-18T00:00:00Z date_updated: 2023-09-07T13:32:32Z day: '18' ddc: - '571' degree_awarded: PhD department: - _id: CaHe - _id: GradSch doi: 10.15479/at:ista:9397 file: - access_level: closed checksum: 7f98532f5324a0b2f3fa8de2967baa19 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: khuljev date_created: 2021-05-17T12:29:12Z date_updated: 2022-05-21T22:30:04Z embargo_to: open_access file_id: '9398' file_name: KHuljev_Thesis_corrections.docx file_size: 47799741 relation: source_file - access_level: open_access checksum: bf512f8a1e572a543778fc4b227c01ba content_type: application/pdf creator: khuljev date_created: 2021-05-18T14:50:28Z date_updated: 2022-05-21T22:30:04Z embargo: 2022-05-20 file_id: '9401' file_name: new_KHuljev_Thesis_corrections.pdf file_size: 16542131 relation: main_file file_date_updated: 2022-05-21T22:30:04Z has_accepted_license: '1' language: - iso: eng month: '05' oa: 1 oa_version: Published Version page: '101' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria status: public supervisor: - first_name: Carl-Philipp J full_name: Heisenberg, Carl-Philipp J id: 39427864-F248-11E8-B48F-1D18A9856A87 last_name: Heisenberg orcid: 0000-0002-0912-4566 title: Coordinated spatiotemporal reorganization of interstitial fluid is required for axial mesendoderm migration in zebrafish gastrulation type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2021' ... --- _id: '9750' abstract: - lang: eng text: Tension of the actomyosin cell cortex plays a key role in determining cell-cell contact growth and size. The level of cortical tension outside of the cell-cell contact, when pulling at the contact edge, scales with the total size to which a cell-cell contact can grow1,2. Here we show in zebrafish primary germ layer progenitor cells that this monotonic relationship only applies to a narrow range of cortical tension increase, and that above a critical threshold, contact size inversely scales with cortical tension. This switch from cortical tension increasing to decreasing progenitor cell-cell contact size is caused by cortical tension promoting E-cadherin anchoring to the actomyosin cytoskeleton, thereby increasing clustering and stability of E-cadherin at the contact. Once tension-mediated E-cadherin stabilization at the contact exceeds a critical threshold level, the rate by which the contact expands in response to pulling forces from the cortex sharply drops, leading to smaller contacts at physiologically relevant timescales of contact formation. Thus, the activity of cortical tension in expanding cell-cell contact size is limited by tension stabilizing E-cadherin-actin complexes at the contact. acknowledged_ssus: - _id: Bio - _id: EM-Fac - _id: SSU acknowledgement: We would like to thank Edouard Hannezo for discussions, Shayan Shami Pour and Daniel Capek for help with data analysis, Vanessa Barone and other members of the Heisenberg laboratory for thoughtful discussions and comments on the manuscript. We also thank Jack Merrin for preparing the microwells, and the Scientific Service Units at IST Austria, specifically Bioimaging and Electron Microscopy, and the Zebrafish Facility for continuous support. We acknowledge Hitoshi Morita for the kind gift of VinculinB-GFP plasmid. This research was supported by an ERC Advanced Grant (MECSPEC) to C.-P.H, EMBO Long Term grant (ALTF 187-2013) to M.S and IST Fellow Marie-Curie COFUND No. P_IST_EU01 to J.S. article_processing_charge: No author: - first_name: Jana full_name: Slovakova, Jana id: 30F3F2F0-F248-11E8-B48F-1D18A9856A87 last_name: Slovakova - first_name: Mateusz K full_name: Sikora, Mateusz K id: 2F74BCDE-F248-11E8-B48F-1D18A9856A87 last_name: Sikora - first_name: Silvia full_name: Caballero Mancebo, Silvia id: 2F1E1758-F248-11E8-B48F-1D18A9856A87 last_name: Caballero Mancebo orcid: 0000-0002-5223-3346 - first_name: Gabriel full_name: Krens, Gabriel id: 2B819732-F248-11E8-B48F-1D18A9856A87 last_name: Krens orcid: 0000-0003-4761-5996 - first_name: Walter full_name: Kaufmann, Walter id: 3F99E422-F248-11E8-B48F-1D18A9856A87 last_name: Kaufmann orcid: 0000-0001-9735-5315 - first_name: Karla full_name: Huljev, Karla id: 44C6F6A6-F248-11E8-B48F-1D18A9856A87 last_name: Huljev - first_name: Carl-Philipp J full_name: Heisenberg, Carl-Philipp J id: 39427864-F248-11E8-B48F-1D18A9856A87 last_name: Heisenberg orcid: 0000-0002-0912-4566 citation: ama: Slovakova J, Sikora MK, Caballero Mancebo S, et al. Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion. bioRxiv. 2020. doi:10.1101/2020.11.20.391284 apa: Slovakova, J., Sikora, M. K., Caballero Mancebo, S., Krens, G., Kaufmann, W., Huljev, K., & Heisenberg, C.-P. J. (2020). Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.11.20.391284 chicago: Slovakova, Jana, Mateusz K Sikora, Silvia Caballero Mancebo, Gabriel Krens, Walter Kaufmann, Karla Huljev, and Carl-Philipp J Heisenberg. “Tension-Dependent Stabilization of E-Cadherin Limits Cell-Cell Contact Expansion.” BioRxiv. Cold Spring Harbor Laboratory, 2020. https://doi.org/10.1101/2020.11.20.391284. ieee: J. Slovakova et al., “Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion,” bioRxiv. Cold Spring Harbor Laboratory, 2020. ista: Slovakova J, Sikora MK, Caballero Mancebo S, Krens G, Kaufmann W, Huljev K, Heisenberg C-PJ. 2020. Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion. bioRxiv, 10.1101/2020.11.20.391284. mla: Slovakova, Jana, et al. “Tension-Dependent Stabilization of E-Cadherin Limits Cell-Cell Contact Expansion.” BioRxiv, Cold Spring Harbor Laboratory, 2020, doi:10.1101/2020.11.20.391284. short: J. Slovakova, M.K. Sikora, S. Caballero Mancebo, G. Krens, W. Kaufmann, K. Huljev, C.-P.J. Heisenberg, BioRxiv (2020). date_created: 2021-07-29T11:29:50Z date_published: 2020-11-20T00:00:00Z date_updated: 2024-03-27T23:30:18Z day: '20' department: - _id: CaHe - _id: EM-Fac - _id: Bio doi: 10.1101/2020.11.20.391284 ec_funded: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/2020.11.20.391284 month: '11' oa: 1 oa_version: Preprint page: '41' project: - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme - _id: 260F1432-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '742573' name: Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation - _id: 2521E28E-B435-11E9-9278-68D0E5697425 grant_number: 187-2013 name: Modulation of adhesion function in cell-cell contact formation by cortical tension publication: bioRxiv publication_status: published publisher: Cold Spring Harbor Laboratory related_material: record: - id: '10766' relation: later_version status: public - id: '9623' relation: dissertation_contains status: public status: public title: Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion type: preprint user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 year: '2020' ...