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Materials Data on MnZn(InS2)4 by Materials Project

MnZn(InS2)4 crystallizes in the monoclinic Cm space group. The structure is two-dimensional and consists of two MnZn(InS2)4 sheets oriented in the (1, 0, 0) direction. Mn2+ is bonded to six S2- atoms to form MnS6 octahedra that share a cornercorner with one ZnS4 tetrahedra, corners with five InS4 tetrahedra, edges with two equivalent MnS6 octahedra, and edges with four equivalent InS6 octahedra. There are a spread of Mn–S bond distances ranging from 2.54–2.64 Å. Zn2+ is bonded to four S2- atoms to form ZnS4 tetrahedra that share a cornercorner with one MnS6 octahedra, corners with two equivalent InS6 octahedra, corners with two equivalent ZnS4 tetrahedra, and corners with four equivalent InS4 tetrahedra. The corner-sharing octahedra tilt angles range from 57–62°. There are a spread of Zn–S bond distances ranging from 2.35–2.41 Å. There are four inequivalent In3+ sites. In the first In3+ site, In3+ is bonded to four S2- atoms to form InS4 tetrahedra that share a cornercorner with one InS6 octahedra, corners with two equivalent MnS6 octahedra, and corners with six InS4 tetrahedra. The corner-sharing octahedra tilt angles range from 58–60°. There are a spread of In–S bond distances ranging from 2.44–2.52 Å. In the second In3+ site, In3+ is bonded to four S2- atoms to form InS4 tetrahedra that share a cornercorner with one MnS6 octahedra, corners with two equivalent InS6 octahedra, and corners with six InS4 tetrahedra. The corner-sharing octahedra tilt angles range from 57–59°. There are one shorter (2.44 Å) and three longer (2.51 Å) In–S bond lengths. In the third In3+ site, In3+ is bonded to six S2- atoms to form InS6 octahedra that share corners with two equivalent ZnS4 tetrahedra, corners with four InS4 tetrahedra, edges with two equivalent InS6 octahedra, and edges with four equivalent MnS6 octahedra. There are a spread of In–S bond distances ranging from 2.60–2.71 Å. In the fourth In3+ site, In3+ is bonded to four S2- atoms to form InS4 tetrahedra that share a cornercorner with one InS6 octahedra, corners with two equivalent MnS6 octahedra, corners with two equivalent InS4 tetrahedra, and corners with four equivalent ZnS4 tetrahedra. The corner-sharing octahedra tilt angles range from 61–66°. There are a spread of In–S bond distances ranging from 2.46–2.53 Å. There are eight inequivalent S2- sites. In the first S2- site, S2- is bonded in a trigonal non-coplanar geometry to two equivalent Zn2+ and one In3+ atom. In the second S2- site, S2- is bonded in a trigonal non-coplanar geometry to one Zn2+ and two equivalent In3+ atoms. In the third S2- site, S2- is bonded to two equivalent Mn2+ and two In3+ atoms to form SMn2In2 tetrahedra that share corners with six SMn2In2 tetrahedra and edges with two equivalent SMnIn3 trigonal pyramids. In the fourth S2- site, S2- is bonded to one Mn2+, one Zn2+, and two equivalent In3+ atoms to form distorted SMnZnIn2 tetrahedra that share corners with six SMn2In2 tetrahedra, corners with three equivalent SMnIn3 trigonal pyramids, and an edgeedge with one SMnIn3 trigonal pyramid. In the fifth S2- site, S2- is bonded in a trigonal non-coplanar geometry to three In3+ atoms. In the sixth S2- site, S2- is bonded in a trigonal non-coplanar geometry to three In3+ atoms. In the seventh S2- site, S2- is bonded in a distorted rectangular see-saw-like geometry to two equivalent Mn2+ and two In3+ atoms. In the eighth S2- site, S2- is bonded to one Mn2+ and three In3+ atoms to form distorted SMnIn3 trigonal pyramids that share corners with three equivalent SMnZnIn2 tetrahedra, corners with two equivalent SMnIn3 trigonal pyramids, and edges with three SMn2In2 tetrahedra.

36 MATERIALS SCIENCE↗

Materials Data on Cr(InS2)2 by Materials Project

Cr(InS2)2 is Spinel structured and crystallizes in the cubic Fd-3m space group. The structure is three-dimensional. Cr2+ is bonded to four equivalent S2- atoms to form CrS4 tetrahedra that share corners with twelve equivalent InS6 octahedra. The corner-sharing octahedral tilt angles are 56°. All Cr–S bond lengths are 2.39 Å. In3+ is bonded to six equivalent S2- atoms to form InS6 octahedra that share corners with six equivalent CrS4 tetrahedra and edges with six equivalent InS6 octahedra. All In–S bond lengths are 2.66 Å. S2- is bonded in a distorted rectangular see-saw-like geometry to one Cr2+ and three equivalent In3+ atoms.

36 MATERIALS SCIENCE↗

Materials Data on InS2 by Materials Project

InS2 is Cubic Laves structured and crystallizes in the cubic Fd-3m space group. The structure is three-dimensional. In3+ is bonded in a 12-coordinate geometry to twelve equivalent S+1.50- atoms. All In–S bond lengths are 3.33 Å. S+1.50- is bonded to six equivalent In3+ and six equivalent S+1.50- atoms to form a mixture of face, edge, and corner-sharing SIn6S6 cuboctahedra. All S–S bond lengths are 2.84 Å.

36 MATERIALS SCIENCE↗

Materials Data on InS2 by Materials Project

InS2 is Rutile structured and crystallizes in the tetragonal P4_2/mnm space group. The structure is three-dimensional. In3+ is bonded to six equivalent S+1.50- atoms to form a mixture of edge and corner-sharing InS6 octahedra. The corner-sharing octahedral tilt angles are 50°. There are four shorter (2.60 Å) and two longer (2.67 Å) In–S bond lengths. S+1.50- is bonded in a distorted trigonal planar geometry to three equivalent In3+ atoms.

36 MATERIALS SCIENCE↗

Materials Data on Yb(InS2)2 by Materials Project

Yb(InS2)2 crystallizes in the orthorhombic Cccm space group. The structure is three-dimensional. Yb2+ is bonded in a 8-coordinate geometry to eight S2- atoms. There are four shorter (2.99 Å) and four longer (3.11 Å) Yb–S bond lengths. In3+ is bonded to four S2- atoms to form edge-sharing InS4 tetrahedra. There are a spread of In–S bond distances ranging from 2.47–2.57 Å. There are two inequivalent S2- sites. In the first S2- site, S2- is bonded in a 4-coordinate geometry to two equivalent Yb2+ and two equivalent In3+ atoms. In the second S2- site, S2- is bonded to two equivalent Yb2+ and two equivalent In3+ atoms to form a mixture of distorted corner and edge-sharing SYb2In2 trigonal pyramids.

36 MATERIALS SCIENCE↗

Materials Data on Mg(InS2)2 by Materials Project

MgIn2S4 is Spinel structured and crystallizes in the cubic Fd-3m space group. The structure is three-dimensional. Mg2+ is bonded to four equivalent S2- atoms to form MgS4 tetrahedra that share corners with twelve equivalent InS6 octahedra. The corner-sharing octahedral tilt angles are 57°. All Mg–S bond lengths are 2.49 Å. In3+ is bonded to six equivalent S2- atoms to form InS6 octahedra that share corners with six equivalent MgS4 tetrahedra and edges with six equivalent InS6 octahedra. All In–S bond lengths are 2.65 Å. S2- is bonded in a distorted rectangular see-saw-like geometry to one Mg2+ and three equivalent In3+ atoms.

36 MATERIALS SCIENCE↗

Materials Data on Zn(InS2)2 by Materials Project

ZnIn2S4 crystallizes in the trigonal P-3m1 space group. The structure is two-dimensional and consists of two ZnIn2S4 sheets oriented in the (0, 0, 1) direction. Zn2+ is bonded to four S2- atoms to form distorted ZnS4 trigonal pyramids that share corners with three equivalent InS6 octahedra and corners with six equivalent ZnS4 trigonal pyramids. The corner-sharing octahedral tilt angles are 62°. There are three shorter (2.27 Å) and one longer (3.16 Å) Zn–S bond lengths. There are two inequivalent In3+ sites. In the first In3+ site, In3+ is bonded to four S2- atoms to form InS4 tetrahedra that share corners with three equivalent InS6 octahedra and corners with six equivalent InS4 tetrahedra. The corner-sharing octahedral tilt angles are 54°. There are one shorter (2.41 Å) and three longer (2.54 Å) In–S bond lengths. In the second In3+ site, In3+ is bonded to six S2- atoms to form InS6 octahedra that share corners with three equivalent InS4 tetrahedra, corners with three equivalent ZnS4 trigonal pyramids, and edges with six equivalent InS6 octahedra. There are three shorter (2.57 Å) and three longer (2.78 Å) In–S bond lengths. There are four inequivalent S2- sites. In the first S2- site, S2- is bonded in a trigonal planar geometry to three equivalent Zn2+ atoms. In the second S2- site, S2- is bonded in a rectangular see-saw-like geometry to four In3+ atoms. In the third S2- site, S2- is bonded in a distorted trigonal non-coplanar geometry to three equivalent In3+ atoms. In the fourth S2- site, S2- is bonded to one Zn2+ and three equivalent In3+ atoms to form distorted corner-sharing SZnIn3 tetrahedra.

36 MATERIALS SCIENCE↗

Materials Data on Zn(InS2)2 by Materials Project

ZnIn2S4 is Spinel structured and crystallizes in the cubic Fd-3m space group. The structure is three-dimensional. Zn2+ is bonded to four equivalent S2- atoms to form ZnS4 tetrahedra that share corners with twelve equivalent InS6 octahedra. The corner-sharing octahedral tilt angles are 56°. All Zn–S bond lengths are 2.41 Å. In3+ is bonded to six equivalent S2- atoms to form InS6 octahedra that share corners with six equivalent ZnS4 tetrahedra and edges with six equivalent InS6 octahedra. All In–S bond lengths are 2.64 Å. S2- is bonded in a distorted rectangular see-saw-like geometry to one Zn2+ and three equivalent In3+ atoms.

36 MATERIALS SCIENCE↗

Materials Data on Mn(InS2)2 by Materials Project

MnIn2S4 is Spinel structured and crystallizes in the cubic Fd-3m space group. The structure is three-dimensional. Mn2+ is bonded to four equivalent S2- atoms to form MnS4 tetrahedra that share corners with twelve equivalent InS6 octahedra. The corner-sharing octahedral tilt angles are 56°. All Mn–S bond lengths are 2.43 Å. In3+ is bonded to six equivalent S2- atoms to form InS6 octahedra that share corners with six equivalent MnS4 tetrahedra and edges with six equivalent InS6 octahedra. All In–S bond lengths are 2.65 Å. S2- is bonded in a distorted rectangular see-saw-like geometry to one Mn2+ and three equivalent In3+ atoms.

36 MATERIALS SCIENCE↗

Materials Data on Zn(InS2)2 by Materials Project

ZnIn2S4 crystallizes in the trigonal P3m1 space group. The structure is two-dimensional and consists of one ZnIn2S4 sheet oriented in the (0, 0, 1) direction. Zn2+ is bonded to four S2- atoms to form ZnS4 tetrahedra that share corners with three equivalent InS6 octahedra and corners with six equivalent ZnS4 tetrahedra. The corner-sharing octahedral tilt angles are 61°. There are three shorter (2.32 Å) and one longer (2.67 Å) Zn–S bond lengths. There are two inequivalent In3+ sites. In the first In3+ site, In3+ is bonded to six S2- atoms to form InS6 octahedra that share corners with three equivalent ZnS4 tetrahedra, corners with three equivalent InS4 tetrahedra, and edges with six equivalent InS6 octahedra. There are three shorter (2.59 Å) and three longer (2.75 Å) In–S bond lengths. In the second In3+ site, In3+ is bonded to four S2- atoms to form InS4 tetrahedra that share corners with three equivalent InS6 octahedra and corners with six equivalent InS4 tetrahedra. The corner-sharing octahedral tilt angles are 56°. There are one shorter (2.46 Å) and three longer (2.51 Å) In–S bond lengths. There are four inequivalent S2- sites. In the first S2- site, S2- is bonded in a trigonal non-coplanar geometry to three equivalent Zn2+ atoms. In the second S2- site, S2- is bonded in a distorted rectangular see-saw-like geometry to four In3+ atoms. In the third S2- site, S2- is bonded to one Zn2+ and three equivalent In3+ atoms to form distorted corner-sharing SZnIn3 tetrahedra. In the fourth S2- site, S2- is bonded in a trigonal non-coplanar geometry to three equivalent In3+ atoms.

36 MATERIALS SCIENCE↗

Materials Data on Zn(InS2)2 by Materials Project

ZnIn2S4 crystallizes in the trigonal R3m space group. The structure is two-dimensional and consists of three ZnIn2S4 sheets oriented in the (0, 0, 1) direction. Zn2+ is bonded to four S2- atoms to form ZnS4 tetrahedra that share corners with three equivalent InS6 octahedra and corners with six equivalent ZnS4 tetrahedra. The corner-sharing octahedral tilt angles are 61°. There are three shorter (2.32 Å) and one longer (2.69 Å) Zn–S bond lengths. There are two inequivalent In3+ sites. In the first In3+ site, In3+ is bonded to six S2- atoms to form InS6 octahedra that share corners with three equivalent ZnS4 tetrahedra, corners with three equivalent InS4 tetrahedra, and edges with six equivalent InS6 octahedra. There are three shorter (2.59 Å) and three longer (2.74 Å) In–S bond lengths. In the second In3+ site, In3+ is bonded to four S2- atoms to form InS4 tetrahedra that share corners with three equivalent InS6 octahedra and corners with six equivalent InS4 tetrahedra. The corner-sharing octahedral tilt angles are 56°. There are one shorter (2.46 Å) and three longer (2.51 Å) In–S bond lengths. There are four inequivalent S2- sites. In the first S2- site, S2- is bonded in a trigonal non-coplanar geometry to three equivalent Zn2+ atoms. In the second S2- site, S2- is bonded in a trigonal non-coplanar geometry to three equivalent In3+ atoms. In the third S2- site, S2- is bonded to one Zn2+ and three equivalent In3+ atoms to form distorted corner-sharing SZnIn3 tetrahedra. In the fourth S2- site, S2- is bonded in a distorted rectangular see-saw-like geometry to four In3+ atoms.

36 MATERIALS SCIENCE↗

Materials Data on Cd(InS2)2 by Materials Project

CdIn2S4 is Spinel structured and crystallizes in the cubic Fd-3m space group. The structure is three-dimensional. Cd2+ is bonded to four equivalent S2- atoms to form CdS4 tetrahedra that share corners with twelve equivalent InS6 octahedra. The corner-sharing octahedral tilt angles are 58°. All Cd–S bond lengths are 2.58 Å. In3+ is bonded to six equivalent S2- atoms to form InS6 octahedra that share corners with six equivalent CdS4 tetrahedra and edges with six equivalent InS6 octahedra. All In–S bond lengths are 2.65 Å. S2- is bonded to one Cd2+ and three equivalent In3+ atoms to form a mixture of distorted edge and corner-sharing SCdIn3 trigonal pyramids.

36 MATERIALS SCIENCE↗

Materials Data on Zn(InS2)2 by Materials Project

ZnIn2S4 crystallizes in the hexagonal P6_3mc space group. The structure is two-dimensional and consists of two ZnIn2S4 sheets oriented in the (0, 0, 1) direction. Zn2+ is bonded to four S2- atoms to form ZnS4 tetrahedra that share corners with three equivalent InS6 octahedra and corners with six equivalent ZnS4 tetrahedra. The corner-sharing octahedral tilt angles are 61°. There are three shorter (2.32 Å) and one longer (2.70 Å) Zn–S bond lengths. There are two inequivalent In3+ sites. In the first In3+ site, In3+ is bonded to four S2- atoms to form InS4 tetrahedra that share corners with three equivalent InS6 octahedra and corners with six equivalent InS4 tetrahedra. The corner-sharing octahedral tilt angles are 56°. There are one shorter (2.46 Å) and three longer (2.51 Å) In–S bond lengths. In the second In3+ site, In3+ is bonded to six S2- atoms to form InS6 octahedra that share corners with three equivalent ZnS4 tetrahedra, corners with three equivalent InS4 tetrahedra, and edges with six equivalent InS6 octahedra. There are three shorter (2.59 Å) and three longer (2.74 Å) In–S bond lengths. There are four inequivalent S2- sites. In the first S2- site, S2- is bonded in a trigonal non-coplanar geometry to three equivalent Zn2+ atoms. In the second S2- site, S2- is bonded in a distorted rectangular see-saw-like geometry to four In3+ atoms. In the third S2- site, S2- is bonded to one Zn2+ and three equivalent In3+ atoms to form distorted corner-sharing SZnIn3 tetrahedra. In the fourth S2- site, S2- is bonded in a trigonal non-coplanar geometry to three equivalent In3+ atoms.

36 MATERIALS SCIENCE↗

Materials Data on Mg(InS2)2 by Materials Project

MgIn2S4 crystallizes in the triclinic P-1 space group. The structure is two-dimensional and consists of one MgIn2S4 sheet oriented in the (0, 0, 1) direction. there are two inequivalent Mg2+ sites. In the first Mg2+ site, Mg2+ is bonded to four S2- atoms to form MgS4 tetrahedra that share a cornercorner with one MgS6 octahedra, corners with two equivalent InS6 octahedra, and corners with six InS4 tetrahedra. The corner-sharing octahedra tilt angles range from 58–59°. There are a spread of Mg–S bond distances ranging from 2.45–2.48 Å. In the second Mg2+ site, Mg2+ is bonded to six S2- atoms to form MgS6 octahedra that share a cornercorner with one MgS4 tetrahedra, corners with five InS4 tetrahedra, edges with two equivalent MgS6 octahedra, and edges with four equivalent InS6 octahedra. There are a spread of Mg–S bond distances ranging from 2.61–2.64 Å. There are four inequivalent In3+ sites. In the first In3+ site, In3+ is bonded to four S2- atoms to form InS4 tetrahedra that share a cornercorner with one InS6 octahedra, corners with two equivalent MgS6 octahedra, corners with two equivalent MgS4 tetrahedra, and corners with four InS4 tetrahedra. The corner-sharing octahedra tilt angles range from 58–61°. There are a spread of In–S bond distances ranging from 2.47–2.53 Å. In the second In3+ site, In3+ is bonded to six S2- atoms to form InS6 octahedra that share corners with two equivalent MgS4 tetrahedra, corners with four InS4 tetrahedra, edges with two equivalent InS6 octahedra, and edges with four equivalent MgS6 octahedra. There are a spread of In–S bond distances ranging from 2.62–2.70 Å. In the third In3+ site, In3+ is bonded to four S2- atoms to form InS4 tetrahedra that share a cornercorner with one InS6 octahedra, corners with two equivalent MgS6 octahedra, corners with two equivalent MgS4 tetrahedra, and corners with four InS4 tetrahedra. The corner-sharing octahedra tilt angles range from 58–61°. There are a spread of In–S bond distances ranging from 2.47–2.54 Å. In the fourth In3+ site, In3+ is bonded to four S2- atoms to form InS4 tetrahedra that share a cornercorner with one MgS6 octahedra, corners with two equivalent InS6 octahedra, corners with two equivalent MgS4 tetrahedra, and corners with four InS4 tetrahedra. The corner-sharing octahedra tilt angles range from 58–61°. There are three shorter (2.49 Å) and one longer (2.53 Å) In–S bond lengths. There are eight inequivalent S2- sites. In the first S2- site, S2- is bonded to two equivalent Mg2+ and two In3+ atoms to form distorted SMg2In2 trigonal pyramids that share corners with seven SMgIn3 tetrahedra, corners with two equivalent SMg2In2 trigonal pyramids, an edgeedge with one SMg2In2 tetrahedra, and edges with two SMg2In2 trigonal pyramids. In the second S2- site, S2- is bonded to two Mg2+ and two equivalent In3+ atoms to form distorted SMg2In2 trigonal pyramids that share corners with seven SMgIn3 tetrahedra, corners with two equivalent SMg2In2 trigonal pyramids, an edgeedge with one SMgIn3 tetrahedra, and edges with two SMg2In2 trigonal pyramids. In the third S2- site, S2- is bonded in a trigonal non-coplanar geometry to one Mg2+ and two In3+ atoms. In the fourth S2- site, S2- is bonded in a trigonal non-coplanar geometry to three In3+ atoms. In the fifth S2- site, S2- is bonded in a trigonal non-coplanar geometry to one Mg2+ and two In3+ atoms. In the sixth S2- site, S2- is bonded in a trigonal non-coplanar geometry to one Mg2+ and two In3+ atoms. In the seventh S2- site, S2- is bonded to one Mg2+ and three In3+ atoms to form distorted SMgIn3 tetrahedra that share corners with two equivalent SMg2In2 tetrahedra, corners with seven SMg2In2 trigonal pyramids, edges with two SMgIn3 tetrahedra, and an edgeedge with one SMg2In2 trigonal pyramid. In the eighth S2- site, S2- is bonded to two equivalent Mg2+ and two In3+ atoms to form distorted SMg2In2 tetrahedra that share corners with two equivalent SMgIn3 tetrahedra, corners with seven SMg2In2 trigonal pyramids, edges with two SMgIn3 tetrahedra, and an edgeedge with one SMg2In2 trigonal pyramid.

36 MATERIALS SCIENCE↗

Materials Data on InGaS3 by Materials Project

In(GaS2)2InS2 crystallizes in the trigonal P3m1 space group. The structure is two-dimensional and consists of one In(GaS2)2 sheet oriented in the (0, 0, 1) direction and one InS2 sheet oriented in the (0, 0, 1) direction. In the In(GaS2)2 sheet, In3+ is bonded to six S2- atoms to form InS6 octahedra that share corners with three equivalent GaS4 tetrahedra and edges with six equivalent InS6 octahedra. There are three shorter (2.55 Å) and three longer (2.83 Å) In–S bond lengths. There are two inequivalent Ga3+ sites. In the first Ga3+ site, Ga3+ is bonded to four S2- atoms to form corner-sharing GaS4 tetrahedra. There are three shorter (2.35 Å) and one longer (2.48 Å) Ga–S bond lengths. In the second Ga3+ site, Ga3+ is bonded to four S2- atoms to form GaS4 tetrahedra that share corners with three equivalent InS6 octahedra and corners with nine GaS4 tetrahedra. The corner-sharing octahedral tilt angles are 53°. There are one shorter (2.21 Å) and three longer (2.44 Å) Ga–S bond lengths. There are four inequivalent S2- sites. In the first S2- site, S2- is bonded to four Ga3+ atoms to form corner-sharing SGa4 tetrahedra. In the second S2- site, S2- is bonded in a rectangular see-saw-like geometry to three equivalent In3+ and one Ga3+ atom. In the third S2- site, S2- is bonded in a distorted trigonal non-coplanar geometry to three equivalent In3+ atoms. In the fourth S2- site, S2- is bonded in a trigonal non-coplanar geometry to three equivalent Ga3+ atoms. In the InS2 sheet, In3+ is bonded to four S2- atoms to form corner-sharing InS4 tetrahedra. There are one shorter (2.38 Å) and three longer (2.56 Å) In–S bond lengths. There are two inequivalent S2- sites. In the first S2- site, S2- is bonded in a single-bond geometry to one In3+ atom. In the second S2- site, S2- is bonded in a distorted trigonal non-coplanar geometry to three equivalent In3+ atoms.

36 MATERIALS SCIENCE↗

Single molecule-based fliFISH validates radial and heterogeneous gene expression patterns in pancreatic islet ß cells

Single cell RNA sequencing (scRNA-Seq) technologies have greatly enhanced our understanding of islet cell transcriptomes and have revealed the existence of ß cell heterogeneity. However, comparison of scRNA-Seq datasets from different groups have highlighted inconsistencies in gene expression patterns, primarily due to variable detection of lower abundance transcripts. Furthermore, such analyses are unable to uncover the spatial organization of heterogeneous gene expression. Here we used fluctuation localization imaging-based fluorescence in situ hybridization (fliFISH) to quantify transcripts in single cells in mouse pancreatic islet sections. We compared the expression patterns of Insulin 2 (Ins2) with Mafa and Ucn3 – two genes expressed in ß cells as they mature, as well as Rgs4 – a factor with variably reported expression in the islet. This approach accurately quantified transcripts across a wide range of expression levels - from single copies to over hundred copies per cell in one islet. Importantly, fliFISH allowed evaluation of transcript heterogeneity in the spatial context of an intact islet. These studies confirm the existence of a high degree of heterogeneous gene expression levels within the islet and highlight relative and radial expression patterns that likely reflect distinct ß cell maturation states along the radial axis of the islet.

Li, Fangjia↗

Renin-Angiotensin System (RAS) in Hematopoietic Stem/Progenitor Cells (HS/PC) Predicts Vaso-Reparative Dysfunction and Progression of Diabetic Retinopathy (DR)

Purpose: We tested the hypothesis that loss of angiotensin converting enzyme 2 (ACE2) within diabetic HS/PCs (Hematopoietic Stem/Progenitor Cells) would be detrimental to HS/PC reparative function, and alter their ability to contribute to vascular remodeling in human subjects and rodent models of DR (Diabetic Retinopathy). Methods: Subjects (n52) were recruited as controls (n13) or diabetics (n39) with either no DR, mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR or proliferative DR (PDR). Fluorescein angiograms were analyzed using Vessel Generation Analysis (VESGEN) software in a cohort of subjects. CD34+ HS/PCs were isolated from peripheral blood. RAS (Renin-Angiotensin System) gene expression and migration was measured. Diabetic ACE2 knockout (KO)C57BL6-Ins2 (Akita) mice at 3, 6 and 9 months of diabetes were compared to age-matched controls. Bone marrow HS/PC populations were analyzed by flow cytometry and migration and proliferation studies performed. Results: ACE2 gene expression in human CD34+ cells from diabetics without DR was increased compared to controls (p0.0437). Mas receptor mRNA was also increased in diabetics without DR, but reduced with the onset of NPDR (p0.0002), suggesting a loss of compensation. DR was associated with CD34+ cell migratory dysfunction. By VESGEN analysis, vessel density measured by several confirming parameters in early NPDR (n3) was greater than in normal retina (n6) in both arteries and veins, which suggests active retinal remodeling. ACE2KO-Akita and Akita cohorts showed reduced retinal thickness by OCT (Optical Coherence Tomography) at 9 months of diabetes. Absence of ACE2 in 9-month Akita mice led to an accelerated increase in acellular capillaries compared to diabetic alone. Electroretinogram (ERG) in ACE2KO-Akita mice resulted in persistent deterioration of the neural retina. Reparative function studies showed that ACE2KO exacerbated diabetes-induced impairment of LK (Low Potassium) cell migration and proliferative functions as early as 3-month of diabetes (p0.0019). Conclusions: Retinopathy and adverse vascular remodeling in subjects with diabetes was associated with a loss of the protective arm of RAS in HS/PCs. Loss of ACE2 exacerbated vascular dysfunction in diabetic mice.

retina↗