Pancreatic Organogenesis Mapped Through Space and Time

Overview

Journal Exp Mol Med

Date 2025 Jan 8

PMID 39779976

Authors

Marissa A Scavuzzo

Wojciech J Szlachcic

Matthew C Hill

Natalia M Ziojla

Jessica Teaw

Jeffrey C Carlson

Jonathan Tiessen

Jolanta Chmielowiec

James F Martin

Malgorzata Borowiak

Affiliations

Soon will be listed here.

Abstract

The spatial organization of cells within a tissue is dictated throughout dynamic developmental processes. We sought to understand whether cells geometrically coordinate with one another throughout development to achieve their organization. The pancreas is a complex cellular organ with a particular spatial organization. Signals from the mesenchyme, neurons, and endothelial cells instruct epithelial cell differentiation during pancreatic development. To understand the cellular diversity and spatial organization of the developing pancreatic niche, we mapped the spatial relationships between single cells over time. We found that four transcriptionally unique subtypes of mesenchyme in the developing pancreas spatially coordinate throughout development, with each subtype at fixed locations in space and time in relation to other cells, including beta cells, vasculature, and epithelial cells. Our work provides insight into the mechanisms of pancreatic development by showing that cells are organized in a space and time manner.

References

Scavuzzo M, Hill M, Chmielowiec J, Yang D, Teaw J, Sheng K . Endocrine lineage biases arise in temporally distinct endocrine progenitors during pancreatic morphogenesis. Nat Commun. 2018; 9(1):3356. PMC: 6105717. DOI: 10.1038/s41467-018-05740-1. View

Katsumoto K, Kume S . The role of CXCL12-CXCR4 signaling pathway in pancreatic development. Theranostics. 2013; 3(1):11-7. PMC: 3563076. DOI: 10.7150/thno.4806. View

Tanaka M, Chen Z, Bartunkova S, Yamasaki N, Izumo S . The cardiac homeobox gene Csx/Nkx2.5 lies genetically upstream of multiple genes essential for heart development. Development. 1999; 126(6):1269-80. DOI: 10.1242/dev.126.6.1269. View

Olaniru O, Kadolsky U, Kannambath S, Vaikkinen H, Fung K, Dhami P . Single-cell transcriptomic and spatial landscapes of the developing human pancreas. Cell Metab. 2022; 35(1):184-199.e5. DOI: 10.1016/j.cmet.2022.11.009. View

Kayali A, Lopez A, Hao E, Hinton A, Hayek A, King C . The SDF-1α/CXCR4 axis is required for proliferation and maturation of human fetal pancreatic endocrine progenitor cells. PLoS One. 2012; 7(6):e38721. PMC: 3382144. DOI: 10.1371/journal.pone.0038721. View

Chmielowiec J, Szlachcic W, Yang D, Scavuzzo M, Wamble K, Sarrion-Perdigones A . Human pancreatic microenvironment promotes β-cell differentiation via non-canonical WNT5A/JNK and BMP signaling. Nat Commun. 2022; 13(1):1952. PMC: 9005503. DOI: 10.1038/s41467-022-29646-1. View

Rodriguez-Diaz R, Dando R, Jacques-Silva M, Fachado A, Molina J, Abdulreda M . Alpha cells secrete acetylcholine as a non-neuronal paracrine signal priming beta cell function in humans. Nat Med. 2011; 17(7):888-92. PMC: 3132226. DOI: 10.1038/nm.2371. View

Rama N, Dubrac A, Mathivet T, Ni Charthaigh R, Genet G, Cristofaro B . Slit2 signaling through Robo1 and Robo2 is required for retinal neovascularization. Nat Med. 2015; 21(5):483-91. PMC: 4819398. DOI: 10.1038/nm.3849. View

Batlle D, Soler M, Ye M . ACE2 and diabetes: ACE of ACEs?. Diabetes. 2010; 59(12):2994-6. PMC: 2992757. DOI: 10.2337/db10-1205. View

10.

Ramilowski J, Goldberg T, Harshbarger J, Kloppmann E, Kloppman E, Lizio M . A draft network of ligand-receptor-mediated multicellular signalling in human. Nat Commun. 2015; 6:7866. PMC: 4525178. DOI: 10.1038/ncomms8866. View

11.

Kratochwil K . Organ specificity in mesenchymal induction demonstrated in the embryonic development of the mammary gland of the mouse. Dev Biol. 1969; 20(1):46-71. DOI: 10.1016/0012-1606(69)90004-9. View

12.

Yoshitomi H, Zaret K . Endothelial cell interactions initiate dorsal pancreas development by selectively inducing the transcription factor Ptf1a. Development. 2004; 131(4):807-17. DOI: 10.1242/dev.00960. View

13.

Sakakura T, NISHIZUKA Y, DAWE C . Mesenchyme-dependent morphogenesis and epithelium-specific cytodifferentiation in mouse mammary gland. Science. 1976; 194(4272):1439-41. DOI: 10.1126/science.827022. View

14.

Hecksher-Sorensen J, Watson R, Lettice L, Serup P, Eley L, De Angelis C . The splanchnic mesodermal plate directs spleen and pancreatic laterality, and is regulated by Bapx1/Nkx3.2. Development. 2004; 131(19):4665-75. DOI: 10.1242/dev.01364. View

15.

Theodosiou N, Tabin C . Sox9 and Nkx2.5 determine the pyloric sphincter epithelium under the control of BMP signaling. Dev Biol. 2005; 279(2):481-90. DOI: 10.1016/j.ydbio.2004.12.019. View

16.

Chung W, Stainier D . Intra-endodermal interactions are required for pancreatic beta cell induction. Dev Cell. 2008; 14(4):582-93. PMC: 2396532. DOI: 10.1016/j.devcel.2008.02.012. View

17.

Scholz B, Korn C, Wojtarowicz J, Mogler C, Augustin I, Boutros M . Endothelial RSPO3 Controls Vascular Stability and Pruning through Non-canonical WNT/Ca(2+)/NFAT Signaling. Dev Cell. 2016; 36(1):79-93. DOI: 10.1016/j.devcel.2015.12.015. View

18.

Larsen B, Hrycaj S, Newman M, Li Y, Wellik D . Mesenchymal Hox6 function is required for mouse pancreatic endocrine cell differentiation. Development. 2015; 142(22):3859-68. PMC: 4712882. DOI: 10.1242/dev.126888. View

19.

Angelo J, Tremblay K . Identification and fate mapping of the pancreatic mesenchyme. Dev Biol. 2018; 435(1):15-25. PMC: 5937278. DOI: 10.1016/j.ydbio.2018.01.003. View

20.

Hibsher D, Epshtein A, Oren N, Landsman L . Pancreatic Mesenchyme Regulates Islet Cellular Composition in a Patched/Hedgehog-Dependent Manner. Sci Rep. 2016; 6:38008. PMC: 5125096. DOI: 10.1038/srep38008. View