Continuous Inhibition of Sonic Hedgehog Signaling Leads to Differentiation of Human-Induced Pluripotent Stem Cells into Functional Insulin-Producing <i>β</i> Cells

<div>Differentiation of pancreatic progenitor cells into IPCs. (a) Final stage of differentiation using forskolin, dexamethasone, and nicotinamide to induce differentiation into IPCs. (b) The insulin and glucagon expression in induced cells assessed using qPCR after 10 d is the highest in cells incubated with SANT-1. The expression profiles of Pdx1 and Nkx6.1 were similar (<span class="nowrap"><svg height="8.55521pt" id="M13" style="vertical-align:-0.2063904pt" version="1.1" viewbox="-0.0498162 -8.34882 27.8368 8.55521" width="27.8368pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M495 86L479 114C446 82 419 66 409 66C401 66 401 72 406 97C420 166 436 231 453 297C489 435 454 448 428 448C406 448 384 439 354 422C305 394 222 327 161 247H159L183 345C200 415 194 448 173 448C143 448 82 410 23 351L38 325C64 349 95 371 105 371C111 371 116 365 109 336L25 -4L31 -12C50 -4 77 3 107 9C119 69 132 122 145 168C197 254 321 381 370 381C387 381 393 374 378 305L329 95C309 17 320 -12 345 -12C372 -12 430 19 495 86Z"></path></g><g transform="matrix(.013,0,0,-0.013,10.158,0)"><path d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"></path></g><g transform="matrix(.013,0,0,-0.013,21.421,0)"><path d="M285 378C315 398 338 416 353 432C373 451 384 474 384 503C384 579 325 635 236 635H235C182 635 136 610 108 579L65 516L85 496C110 533 150 575 205 575C258 575 300 543 300 481C300 407 232 369 141 339L147 310C163 315 188 321 211 321C268 321 338 284 338 192C338 94 288 40 217 40C160 40 119 68 93 91C85 98 77 97 69 91C60 84 47 71 46 58C44 46 48 35 62 22C75 10 116 -12 162 -12C234 -12 424 62 424 224C424 297 373 359 285 376V378Z"></path></g></svg>).</span> (c) Immunostaining of cells expressing insulin or glucagon on day 10 of differentiation step 3. (d) Insulin or Pdx1 expression on day 10 of differentiation step 3. (e) Distribution of cells expressing insulin, glucagon, and Ngn3 in differentiated cells analyzed by FACS.</div>

Stem Cells International

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Figure 4: Continuous Inhibition of Sonic Hedgehog Signaling Leads to Differentiation of Human-Induced Pluripotent Stem Cells into Functional Insulin-Producing <i>β</i> Cells 

Figure 4 | Continuous Inhibition of Sonic Hedgehog Signaling Leads to Differentiation of Human-Induced Pluripotent Stem Cells into Functional Insulin-Producing β Cells 