Table 1.
Beta cell subpopulations identified in human pancreatic islets
| Beta cell subpopulation (INS +) | Gene expression profile | Beta cell maturity | Beta cell functionality | Percentage | In diseased and normal conditions | Used method | References |
|---|---|---|---|---|---|---|---|
| ST8SIA1− | High GLUT2 expression | Mature | Improved insulin secretion | ~ 85% | Reduced in T2D |
FACS live sorting (HPi2 + /HPa3-) |
Dorrell et al. [37] |
| ST8SIA1+ |
Low GLUT2 expression High K + channel expression High f-channel HCN1 SIX3, RFX6, MAFB and NEUROD1 |
Immature | Reduced insulin secretion | ~ 15% | Increased in T2D | ||
| PDX1high/INShigh | GLUT1, MAFA, MAFB, BMP5, TGFBR3, GREM1, DACH2, IRX3, DLK1, FOXN2, ITGB7, GCGR, IAPP, CAPN13, G6PC2, TIPRL, CALML4, MAPK1, SIRT1, REG1A, BMF, CFLAR, DDX58, SLC2A2, SLC6A6, SLC6A15, SLC17A6, SLC39A11, SLC38A6, SLC16A10, SLC25A19 | Mature | Improved insulin secretion | 78.3% | – | Pdx1mRFP-Ins1eGFP dual reporter lentiviral vector | Szabat et al. [35] |
| PDX1+/INSlow | PRG-3, IRX2, MSI2, VIL1, RFX2, BAMBI, FSTL5, VIM, FOXP4, CD39, MUC13, LAMB1, SNPH, CAMK2G, MAPK4, PPY, SST, GHRL, SORBS1, DPP4, LEPR, SIRT5, TRIB3, CHN2, FAP, TM4SF4, PRP4A3, ALK, CARD11, DAP, DFFA, SLC5A1, SLC40A1, SLC44A3, SLC22A4, SLC7A14, SLC35F4 | Immature, Increased proliferation, a small percentage of these cells slowly mature into PDX1high/INShigh (9.3%) | Reduced insulin secretion | 21% | – | ||
| INSlo UPRlo | ID1, ID3, ID4, JUNB, CEBPD, SIX3, TSHZ2, FOS, EGR1, MLXIPL, NFIC, YBX1, KLF6, ZFP36L2, MLLT11, SIX3, HES1, KMT2E, TSC22D1, ISL1, NKX2-2, GTF3A, ZNF580, NEUROD1 | – | Low insulin secretion | 16% | Increase after stress resolve | Single-cell RNA sequencing and pseudotime analysis | Xin et al. [41] |
| INShi UPRlo | SOD3, MAFA | – | High insulin secretion | 38% | Decrease in stress conditions and insulin demand | ||
| INSlo UPRhi | SOD1, SOD2, CD44, GCLM, GSTP1, GLRX2, GLRX3, GPX1, GPX2, GPX3, GPX4, SLC3A2, PRDX1, PRDX2, PRDX6, TXN, TXNL1, TXNRD1, NQO1, FTH1, FTL, PCBP1, SQSTM1, PARK7, CDKN1A, MANF, ID1-3, ID2, ATF3, ATF4, CREM, JUN, NFKBIA, TBPL1, ELF3, DBP, ZNF622, ARID5B, ENO1, HMGA1, NR0B1, CEBPG, DDIT3, NR3C1, TSC22D1, ZNF511, TAX1BP1, CDC5L, LYAR, PHF5A, ZC3H15, ZBTB2, DNAJC2, ZNF410, TFB2M, ZNF830, ZNF22, MAF1, ZNF593, GTF3A, DRAP1, PHB, SFPQ, YBX1, KLF6, HES1, BHLHE40, ZNF331, ZNF326, CAMTA2, ZNF143, EGR4, YBX3, MATR4, CREB3, CEBPB, HES4, ZNF207, SMARCE1, XBP1, ZNF706 | Increased proliferation and metabolic demands | Low insulin secretion | ~ 23% | Increase in stress conditions and high insulin demands | ||
| C1 | Higher PDX1 expression* | Quiescent | High insulin expression* | 10–70% | Increase with age and decrease with obesity | Mass cytometry | Wang et al. [34] |
| C2 | CD44 high, CD49F high, CD9, CYP26A1, PDGFRA, pERK1/2, pSTAT3, pSTAT5, Ki67 | Increased proliferation | – | 5–55% | Decrease in T2D | ||
| C3 | CD44, CD49F, CD9, CYP26A1, Ki67 | Increased proliferation | – | 20–100% | Decrease with age | ||
| C1 | RBP4, FFAR4, ID1, ID3 | – | Correlate with insulin resistance | ~ 22% | Increase in obese and T2D individuals | single-cell RNA-sequencing | Segerstolpe et al. [43] |
| C2 | ID1, ID3 | – | – | ~ 7% | – | ||
| C3 | ID1, ID3 | – | – | ~ 19% | – | ||
| C4 | ID2 | – | – | ~ 13% | – | ||
| C5 | RBP4, FFAR4 | – | Correlate with insulin resistance | ~ 39% | Increase in obese and T2D individuals | ||
| βHI |
High nuclear compaction High H3K27me3 expression High insulin content High CD24 surface marker expression High mitochondrial content High insulin secretory function |
Increased proliferation | – | ~ 30–90% | Increase in T2D | FACS, single-cell RNA-sequencing, and SCAN-seq | Dror et al. [54] |
| βLO |
Low H3K27me3 expression Low CD24 surface marker expression |
– | – | ~ 10–70% | – | ||
| CD24high |
Highest CD24 surface marker expression High INS and SST expression |
– | – | ~ 1% | – |
UPR unfolded protein response, C clusters identified