dc.contributor.author | Fahd Qadir, Mirza Muhammad | |
dc.contributor.author | Álvarez-Cubela, Silvia | |
dc.contributor.author | Klein, Dagmar | |
dc.contributor.author | van Dijk, Jasmijn | |
dc.contributor.author | Muñiz-Anquela, Rocío | |
dc.contributor.author | Moreno-Hernández, Yaisa B. | |
dc.contributor.author | Lanzoni, Giacomo | |
dc.contributor.author | Sadiq, Saad | |
dc.contributor.author | Navarro-Rubio, Belén | |
dc.contributor.author | García, Michael T. | |
dc.contributor.author | Johnson, Kevin | |
dc.contributor.author | Sant, David | |
dc.contributor.author | Ricordi, Camilo | |
dc.contributor.author | Griswold, Anthony | |
dc.contributor.author | Pastori, Ricardo Luis | |
dc.contributor.author | Domínguez-Bendala, Juan | |
dc.date.accessioned | 2021-10-27T10:38:00Z | |
dc.date.available | 2021-10-27T10:38:00Z | |
dc.date.issued | 2020 | |
dc.identifier.issn | 0027-8424 | spa |
dc.identifier.uri | http://hdl.handle.net/10641/2521 | |
dc.description.abstract | We have described multipotent progenitor-like cells within the major pancreatic ducts (MPDs) of the human pancreas. They express PDX1, its surrogate surface marker P2RY1, and the bone morphogenetic protein (BMP) receptor 1A (BMPR1A)/activin-like kinase 3 (ALK3), but not carbonic anhydrase II (CAII). Here we report the single-cell RNA sequencing (scRNA-seq) of ALK3bright+-sorted ductal cells, a fraction that harbors BMP-responsive progenitor-like cells. Our analysis unveiled the existence of multiple subpopulations along two major axes, one that encompasses a gradient of ductal cell differentiation stages, and another featuring cells with transitional phenotypes toward acinar tissue. A third potential ducto-endocrine axis is revealed upon integration of the ALK3bright+ dataset with a single-cell whole-pancreas transcriptome. When transplanted into immunodeficient mice, P2RY1+/ALK3bright+ populations (enriched in PDX1+/ALK3+/CAII− cells) differentiate into all pancreatic lineages, including functional β-cells. This process is accelerated when hosts are treated systemically with an ALK3 agonist. We found PDX1+/ALK3+/CAII− progenitor-like cells in the MPDs of types 1 and 2 diabetes donors, regardless of the duration of the disease. Our findings open the door to the pharmacological activation of progenitor cells in situ. | spa |
dc.language.iso | eng | spa |
dc.publisher | PNAS | spa |
dc.rights | Atribución-NoComercial-SinDerivadas 3.0 España | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.subject | human pancreatic progenitors | spa |
dc.subject | type 1 diabetes | spa |
dc.subject | islet regeneration | spa |
dc.subject | transplantation | spa |
dc.subject | single-cell RNA | spa |
dc.subject | sequencing | spa |
dc.title | Single-cell resolution analysis of the human pancreatic ductal progenitor cell niche. | spa |
dc.type | journal article | spa |
dc.type.hasVersion | AM | spa |
dc.rights.accessRights | open access | spa |
dc.description.extent | 3.184 KB | spa |
dc.identifier.doi | 10.1073/pnas.1918314117 | spa |
dc.relation.publisherversion | https://www.pnas.org/content/117/20/10876 | spa |