TY - JOUR
T1 - Single-cell transcriptomic and spatial landscapes of the developing human pancreas
AU - Olaniru, Oladapo Edward
AU - Kadolsky, Ulrich
AU - Kannambath, Shichina
AU - Vaikkinen, Heli
AU - Fung, Kathy
AU - Dhami, Pawan
AU - Persaud, Shanta J.
N1 - Funding Information:
We thank the Joint MRC/Wellcome Trust (grant# MR/R006237/1) Human Developmental Biology Resource (http://hdbr.org) for provision of the human fetal pancreatic material. We acknowledge assistance from NIHR Guy's and St Thomas’ Biomedical Research Centre Flow Cytometry Core Facility and Genomics Centre. O.E.O. was supported by a Novo Nordisk UK Research Foundation grant and an NC3Rs Early Career Support Award. Research design, O.E.O. and S.J.P.; O.E.O. conducted experiments. H.V. K.F. and P.D. prepared scRNA-seq and 10x Visium libraries. O.E.O. U.K. S.K. and S.J.P. performed data analysis. O.E.O. and S.J.P. wrote or contributed to the writing of the manuscript. All authors revised the manuscript critically for important intellectual content and gave their approval for the current version to be published. O.E.O. and S.J.P. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research.
Funding Information:
We thank the Joint MRC/Wellcome Trust (grant# MR/R006237/1 ) Human Developmental Biology Resource ( http://hdbr.org ) for provision of the human fetal pancreatic material. We acknowledge assistance from NIHR Guy’s and St Thomas’ Biomedical Research Centre Flow Cytometry Core Facility and Genomics Centre. O.E.O. was supported by a Novo Nordisk UK Research Foundation grant and an NC3Rs Early Career Support Award .
Publisher Copyright:
© 2022 The Author(s)
PY - 2023/1/3
Y1 - 2023/1/3
N2 - Current differentiation protocols have not been successful in reproducibly generating fully functional human beta cells in vitro, partly due to incomplete understanding of human pancreas development. Here, we present detailed transcriptomic analysis of the various cell types of the developing human pancreas, including their spatial gene patterns. We integrated single-cell RNA sequencing with spatial transcriptomics at multiple developmental time points and revealed distinct temporal-spatial gene cascades. Cell trajectory inference identified endocrine progenitor populations and branch-specific genes as the progenitors differentiate toward alpha or beta cells. Spatial differentiation trajectories indicated that Schwann cells are spatially co-located with endocrine progenitors, and cell-cell connectivity analysis predicted that they may interact via L1CAM-EPHB2 signaling. Our integrated approach enabled us to identify heterogeneity and multiple lineage dynamics within the mesenchyme, showing that it contributed to the exocrine acinar cell state. Finally, we have generated an interactive web resource for investigating human pancreas development for the research community.
AB - Current differentiation protocols have not been successful in reproducibly generating fully functional human beta cells in vitro, partly due to incomplete understanding of human pancreas development. Here, we present detailed transcriptomic analysis of the various cell types of the developing human pancreas, including their spatial gene patterns. We integrated single-cell RNA sequencing with spatial transcriptomics at multiple developmental time points and revealed distinct temporal-spatial gene cascades. Cell trajectory inference identified endocrine progenitor populations and branch-specific genes as the progenitors differentiate toward alpha or beta cells. Spatial differentiation trajectories indicated that Schwann cells are spatially co-located with endocrine progenitors, and cell-cell connectivity analysis predicted that they may interact via L1CAM-EPHB2 signaling. Our integrated approach enabled us to identify heterogeneity and multiple lineage dynamics within the mesenchyme, showing that it contributed to the exocrine acinar cell state. Finally, we have generated an interactive web resource for investigating human pancreas development for the research community.
KW - beta cell development
KW - endocrine progenitors
KW - human fetal pancreas
KW - Schwann cells
KW - scRNA-seq
KW - spatial transcriptomics
KW - trajectory inference
KW - Visium
UR - https://www.scopus.com/pages/publications/85144997822
U2 - 10.1016/j.cmet.2022.11.009
DO - 10.1016/j.cmet.2022.11.009
M3 - Article
C2 - 36513063
AN - SCOPUS:85144997822
SN - 1550-4131
VL - 35
SP - 184-199.e5
JO - Cell Metabolism
JF - Cell Metabolism
IS - 1
ER -