LectureNote

ÀÖ·ìµå·Ï¤·ìºÙ˦ erythroid cells

ÀÖ·ìµå·Ï¤ÎºÙ˦¤ÏÀÖ²êµå·ÏÁ°¶îºÙ˦¢ªÁ°ÀÖ²êµå¢ªÀÖ²êµå¢ªÌÖÀÖ·ìµå¢ªÀÖ·ìµå¤Ø¤Èʬ²½*1¤¹¤ë

ÀÖ·ìµå·Ï¤ÎºÙ˦¤Ï¹ü¿ñ¤Ç3-4ÆüÁý¿£¤·,À®½Ï¤Î¤¿¤á1-2Æü¹ü¿ñ¤Ë¤È¤É¤Þ¤ê,ÌÖÀÖ·ìµå¤Î·Á¤ÇËö¾¿·ì¤ËÊü½Ð¤µ¤ì¤ë¡£

ÀÖ²êµå·ÏÁ°¶îºÙ˦

¹ü¿ñµå·Ï¶¦ÄÌÁ°¶îºÙ˦¤«¤éÁ°ÀÖ²êµå¤Þ¤Ç¤ÏÆÃ°ÛŪ¤Ê¥Þ¡¼¥«¤¬¤Ê¤¯·ÁÂÖŪ¤Ë¤â²êµåÍͤò¼¨¤·Â¾¤Î·ÏÅý¤ÎÁ°¶îºÙ˦¤È¶èÊ̤¹¤ë¤³¤È¤Ïº¤Æñ¤Ç¤¢¤Ã¤¿.¥³¥í¥Ë¡¼¥¢¥Ã¥»¥¤Ë¡¤Ï, ¤³¤ÎÃʳ¬¤ÎÁ°¶îºÙ˦¤Î¼ïÎप¤è¤Ó¿ô¤òȽÃǤ¹¤ë¤³¤È¤¬¤Ç¤­¤¿¡£

¥³¥í¥Ë¡¼¥¢¥Ã¥»¥¤Ë¡¤Ë¤è¤êÀÖ²êµåÀ­Á°¶îºÙ˦¤Ë¤Ï£²¼ïÎढ¤ë¤³¤È¤¬¤ï¤«¤Ã¤¿

  • £±¡¥BFU-E: burst-forming-unit-erythroid
    ¤·ì´´ºÙ˦¤è¤êÇÉÀ¸¤¹¤ë¹ü¿ñ·Ï¤ÎºÇ¤âÍļã¤ÊÁ°¶îºÙ˦¤Ç¤¢¤ëCFU-mix¤«¤éʬ²½À®½Ï¤·¤Æ¤Ç¤­¤ë¡£ÀÖ²êµå·Ï¤ÎºÇ¤âÍļã¤ÊºÙ˦.¹ü¿ñºÙ˦¤òÇ´Ä´¤ÊÇÝÃϤǥ¨¥ê¥¹¥í¥Ý¥¤¥¨¥Á¥ó(EPO)ÂçÎ̸ºß²¼¤ËÇÝÍܤ·¤ÆÌó14Æü¤Ë´Ñ»¡¤µ¤ì¤ë.
     
  • £²¡¥CFU-E: colony-forming-unit-erythroid
    ʬ²½¤¬¤¢¤ëÄøÅٿʤó¤ÀÁ°¶îºÙ˦¤Ç,¥¨¥ê¥¹¥í¥Ý¥¤¥¨¥Á¥ó(EPO)¸ºß²¼¤Ç7ÆüÌܤ˾®·¿¤ÎÀÖ²êµå¥³¥í¥Ë¡¼¤ò·ÁÀ®¤¹¤ë. BFU-E¤«¤éCFU-E¤Ø¤Îʬ²½¤Ïmulti-CSF¤ËÂФ¹¤ë°Í¸À­¤¬EPO°Í¸À­¤ËÊÑ´¹¤·¤Æ¤¤¤­CFU-E¤ÏEPO¤ÎºîÍѤÇÀÖ²êµå¤Ëʬ²½¤¹¤ë.
     

¸½ºß¤Ï, multi-color FACS¤È¿·µ¬¹³ÂΤˤè¤ê, ÀÖ²êµå·ÏÁ°¶îºÙ˦¤ÎƱÄ꤬¤ª¤³¤Ê¤ï¤ì¤ë¤è¤¦¤Ë¤Ê¤Ã¤¿.*2

¿¹¤é¤Ï, ¥Ò¥È¤·ì¥·¥¹¥Æ¥à¤Ë¤ª¤¤¤Æ, CD71¤ÈCD105¤òÄɲä·¤¿multi-color FACS¤Ë¤è¤ê¹ü¿ñÃæ¤ËÀÖ²êµå·ÏÅýÆÃ°ÛŪÁ°¶îºÙ˦(erythroid progenitor;EP*3)¤òñΥ¤·, ¤½¤Îʬ²½·ÐÏ©/ʬ²½µ¡¹½¤Ë¤Ä¤¤¤Æ¸¡Æ¤¤·¤Æ¤¤¤ë.

revised-human EP.jpg
  • CD71 transferrin receptor¡¨µÙ»ß´ü¤ÎºÙ˦¤Ë¤Ïȯ¸½¤»¤º, ¼ï¡¹¤Î³èÀ­²½ºÙ˦¤Ëȯ¸½¤¹¤ë. Fe¤òÂçÎ̤ËÂå¼Õ¤¹¤ëɬÍפΤ¢¤ëÁá´ü¤ÎÀÖ²êµå·ÏºÙ˦¤Ëȯ¸½¤¹¤ëɽÌÌ¥Þ¡¼¥«¤È¤·¤ÆÃΤé¤ì¤Æ¤¤¤ë.(ÀÖ²êµå·Ï¤Î¤ß¤Ç¤Ï¤Ê¤¤¤³¤È¤ËÃí°Õ)
  • CD105 endoglin; TGF-¦Â¤Î­··¿¼õÍÆÂÎÊ£¹çÂι½À®Í×ÁǤΰì¤Ä¤ÇCD71¤ÈƱ¤¸¤¯Ê¬²½½é´ü¤ÎÀÖ²êµå·ÏºÙ˦(CD34ÍÛÀ­)¤Ëȯ¸½¤¹¤ëɽÌÌ¥Þ¡¼¥«
     
    • CD71¤ÏMEP(Megakaryocyte/erythrocyte progenitor)¤è¤ê¾åή¤ÎCMP(common myeloid progenitor)¥ì¥Ù¥ë¤«¤éȯ¸½¤·¤Æ¤¤¤ë(31.5¡Þ11.1%). MEP¤Ç¤ÏÂçÉôʬ¤¬ÍÛÀ­¤Ç¤¢¤Ã¤¿(82.3¡Þ6.4%)
       
    • CD105¤ÎÍÛÀ­¤¬³Îǧ¤µ¤ì¤¿¤Î¤Ï CD71ÍÛÀ­MEP¤Î¤ß¤Ç¤¢¤Ã¤¿.
       
    • CD71±¢À­CMP¤ÈÈæ³Ó¤·¤ÆCD71+ CMP¤Ïµð³Ëµå¡¦ÀÖ²êµå·Ï¤ØÊФä¿Ê¬²½Ç½¤ò¼¨¤·¤¿.
       
    • CD71+, CD105- MEP¤ÏMgk¤Ø¤Îʬ²½Ç½¤ò¤ï¤º¤«¤Ë»Ä¤·¤Ê¤¬¤é¼ç¤È¤·¤ÆBFU-E¤ò·ÁÀ®¤·¤¿¤Î¤ËÂФ·¤Æ, CD71+, CD105+ MEP¤ÏCFU-E¼çÂΤËerythroid-colony¤Î¤ß¤ò·ÁÀ®¤·¤ÆMgk¥Ý¥Æ¥ó¥·¥ã¥ë¤ò¼º¤Ã¤Æ¤¤¤ë.
       
    • µð³Ëµåʬ²½¤ËŬ¤·¤¿Ìµ·ìÀ¶±ÕÂÎÇÝÍܲ¼¤Ç¤âCD71+, CD105+ MEP¤«¤é¤ÏGlycophorin-A+¤Î¤ß¤ÎÀÖ²êµå¤¬»ºÀ¸¤µ¤ìCD41+¤ÎMgk»ºÀ¸Ç½¤Ï³Îǧ¤Ç¤­¤Ê¤«¤Ã¤¿.
       
    • °Ê¾å¤Î·ë²Ì¤è¤êCD71+,CD105- MEP¤¬Erythroid-biased MEP(E-MEP)¤Ç¤¢¤êCD71+, CD105+ MEP¤¬¥Ò¥ÈEP¤È¤·¤ÆÆ±Äꤵ¤ì¤¿
       
    • ½¾Íè¤ÎMEPʬ²è&note;¤ÏÉԶѰì¤ÊºÙ˦½¸ÃĤǤ¢¤ê, bi-potent¤ÊMEP¤Ï Lin- CD105-, CD34+ CD38+ IL-3R¦Á- CD45RA-Ãæ¤Î¤ß¤Ë¸ºß¤¹¤ë¤³¤È¤Ë¤Ê¤ë.

¥Ò¥ÈEP(erythroid-progenitor)=CD71+ CD105+ MEP¤Îʬ²½·ÐÏ©

  • CD71- CMP¤Ïû´ü±ÕÂÎÇÝÍܷϤˤª¤¤¤ÆÇÝÍÜ3ÆüÌܤËCD71+ CMP¤Î¤Û¤«, ðùγµå¡¦Ã±µå·ÏÁ°¶îºÙ˦(granulocyte/macrophage progenitor, GMP)¤äMEP¤Ø¤Îʬ²½¤¬³Îǧ¤µ¤ì¤ë.
     
  • CD71+ CMP¤«¤é¤ÏCD105ÍÛÀ­EPʬ²è¤ò´Þ¤àMEP¤Ø¤Î¸ÂÄêŪʬ²½Ç½¤¬¼¨¤µ¤ì, GMP¤Ï½Ð¸½¤·¤Ê¤¤.
     
  • CD71+ CMP¤ÏCD71- CMP¤«¤éMEP¤Ø¸þ¤«¤¦Ãæ´ÖÃʳ¬¤Ë¸ºß¤¹¤ë¤È¹Í¤¨¤é¤ì¤¿.
     
  • CD105- MEP¤«¤éCD105+ MEP(EP)¤Ø¤Î°ìÊý¸þŪʬ²½¤¬³Îǧ¤µ¤ì¥Ò¥ÈEP¤¬CD105-MEP¤Î²¼Î®¤Ë¸ºß¤¹¤ë¤³¤È¤¬ÌÀ¤é¤«¤Ë¤Ê¤Ã¤¿.
     
  • CD71- CD105- MEP¤ÈCD71¡Ü CD105- MEP(E-MEP)¤Ë¤ÏÁÐÊý¸þÀ­Ê¬²½¤¬´Ñ»¡¤µ¤ìCD71- CMP¤«¤éCD71+ CMP¤ò·Ðͳ¤»¤ºÄ¾ÀܤËCD71-MEP¤Ë¸þ¤«¤¦¥Þ¥¤¥Ê¡¼¤Ê·ÐÏ©¤Î¸ºß¤â¼¨º¶¤µ¤ì¤¿.

Á°ÀÖ²êµå proerythroblasts

 
erythroblast.jpg
  • ·ÁÂÖ³ØÅª¤ËÀÖ·ìµå·Ï¤ÈȽÃǤǤ­¤ë¤â¤Ã¤È¤â̤½Ï¤ÊºÙ˦¤Ç4²ó¤ÎϢ³¤¹¤ëºÙ˦ʬÎö¤ò·Ð¤Æ¥Ø¥â¥°¥í¥Ó¥ó²½¤µ¤ì̵³ËÀÖ·ìµå¤È¤Ê¤ë
     
  • Proerythroblast(¥×¥í¥¨¥ê¥¹¥í¥Ö¥é¥¹¥È)¤Þ¤¿¤Ïrubriblast(¥ë¥Ö¥ê¥Ö¥é¥¹¥È, rubri-->rubyÀÖ)¤È¸Æ¤Ö¡£
     
  • ľ·Â20¦Ìm¤Û¤É¡¥ÀÖ²êµå·ÏºÙ˦¤Ç¤ÏºÇÂç. Îà±ß·Á¤Î³Ë¤òºÙË¦Ãæ¿´¤Ë¤â¤Ä.¥¯¥í¥Þ¥Á¥ó¤ÏÁ¡ºÙðùγ¾õ¤Ç¥¢¥º¥­¿§¤ÎÅÀÉÁ¤Î¤è¤¦¤Ë¸«¤¨¤ë.³Ë¤Ë¤ÏÀĤߤζ¯¤¤³Ë¾®ÂΤò2-3¸Ä¤â¤Ä.
     
  • ºÙ˦¼Á¤Ïpolysome(RNA¤ËÉÙ¤àribosome¤¬¿ô¸Ä¤º¤Ä½¸¤Þ¤ê½¸²ô¤òºî¤ë)¤¬Â¿¤¯Á´Ì̺°ÀÄ¿§¤òÄ褹¤ë. ¤¿¤À¤·Á°¶îºÙ˦¤è¤êʬ²½¤·¤¿¤Ð¤«¤ê¤Ç¤Ïpolysome¤òÁý¤ä¤¹Ãʳ¬¤Ç¤Þ¤ÀºÙ˦¼Á¤ÎÀÄ¿§Ä´¤ÏÇ»¤¯¤Ê¤Ã¤Æ¤¤¤Ê¤¤¤³¤È¤ËÃí°Õ.
     
  • ºÙ˦¼ÁÊÕ±ï¤Ë¤Ï,áî¾õ¤Îbleb(blister¤È¤â¤è¤Ö¡Ë¤ò·ÁÀ®¤¹¤ë¤³¤È¤¬¤¢¤ë¡£¤³¤ì¤¬¤¢¤ì¤Ð¤³¤ÎÍļãºÙ˦¤¬Á°ÀÖ²êµå¤Î²ÄǽÀ­¤¬¤¢¤ë.
     
  • proerythroblasts¤ÎÍÛÀ­¥Þ¡¼¥«(FCM)¤Ï, CD36, CD38, CD45, CD71, CD117, glycophorin (CD235a; dim), HLA-DR (moderate) ¤ÇCD34¤Îȯ¸½¤â¤¢¤ê¤¦¤ë.*4

ÀÖ²êµå erythroblasts

 
  • ÀÖ·ìµå·Ï¤Îʬ²½¤¬¿Ê¤à¤Ë¤Ä¤ì¤Æ¥Ø¥â¥°¥í¥Ó¥óÎ̤¬Áý²Ã¤¹¤ë¤¿¤á¤ËºÙ˦¼Á¤¬ÀÖ¤¯À÷¤Þ¤ë¤è¤¦¤Ë¤Ê¤ë¡£
     
  • ¤³¤Î¤¿¤áÁ°ÀÖ²êµå°Ê¹ß¤ÎÀÖ·ìµåºÙ˦¤ò·ÁÂÖ³ØÅª¤Ë¹¥±ö´ðÀ­ÀÖ²êµå, ¿À÷À­ÀÖ²êµå, ÀµÀ÷À­ÀÖ²êµå¤Î£³¤Ä¤ËʬÎह¤ë¤¬,¡¡¤³¤ÎÃʳ¬¤ï¤±¤Ï¤¢¤Þ¤ê½ÅÍפǤϤʤ¤
     
    ¡úÀÖ²êµå¡§²êµå¤È¤ÏËÜÍè,ºÙ˦·ÁÂÖŪ¤ËʬÎàÆ±Äꤷ¤¦¤ëºÇ¤âÍļå¤ÊÃʳ¬¤ÎºÙ˦¤ò¤¤¤¦¤¬, ÀÖ²êµå¤ÏÍ­³ËÀÖ·ìµå¤Î¤³¤È¤Ç¤¢¤ê, Ʊ¤¸°ÕÌ£¤Î¤â¤Î¤Ç¤Ï¤Ê¤¤¡£erythropoiesis¤ÇËÜÍè¤Î²êµå¤Ë¤¢¤¿¤ë¤â¤Î¤Ïproerythroblast(Á°ÀÖ²êµå)¤Ç¤¹¡£
     
  • EPO¤Ë»Ù»ý¤µ¤ì¤¿CFU-E¤Ï3-4²óʬÎö¤·Á°ÀÖ²êµå¢ªÀÖ²êµå¤Ø¤Îʬ²½¤¬¤¹¤¹¤ßHbÃßÀÑ, ÆÃ°ÛŪËìÀÖ·ìµå¹½Â¤·ÁÀ®, ¹¥µ¤À­¤«¤é·ùµ¤À­Âå¼Õ¤Ø¤ÎÊѲ½¤¬¸«¤é¤ìæ³Ë¤¹¤ë
     
  • ³Ë¤ÏÀÖ²êµåºÙ˦¼Á¤Î°ìÊý¤Ë²¡¤·¤ä¤é¤ìºÇ¸å¤ÏºÙ˦Ëì¤ÈºÙ˦¼Á¤Î°ìÉô¤ò¤È¤â¤Ê¤¤Ê¬Î¥Êü½Ð¤µ¤ì¤ë. Êü½Ð¤µ¤ì¤¿³Ë¤ÏÃæ¿´¥Þ¥¯¥í¥Õ¥¡¡¼¥¸¤¬¼è¤ê¹þ¤ßʬ²ò½èÍý¤ò¤¹¤ë¡£
     

ÌÖÀÖ·ìµå reticulocytes

reticulocyte.jpg
 

ÌÖÀÖ·ìµå¤ÏÀ®½ÏÀÖ·ìµå¤è¤êÂ礭¤¯8-10¦Ìm¤ÇGiemsa¤äwrightÀ÷¿§¤Ç¤Ï¤ä¤äÀĤߤ¬¤«¤Ã¤¿Â¿À÷À­¤ÎÀÖ·ìµå¤È¤·¤Æ´Ñ»¡¤Ç¤­¤ë. À¸Âγ°¤Ë¤È¤ê¤À¤·¤¿ÌÖÀÖ·ìµå¤Î»î¸³´ÉÆâȾÀ¸Â¸»þ´Ö¤Ï4.8¡Þ1.9»þ´Ö¤È¤¤¤ï¤ì¤ë.

À¸Âγ°¤ÎÀ¸¤­¤¿¤Þ¤Þ¤ÎÀÖ·ìµå¤òÀ÷¿§¤¹¤ëĶÀ¸ÂÎÀ÷¿§¤Ë¤è¤êRNA¤ò´Þ¤à¥ß¥¯¥í¥½¡¼¥à¤¬ÌÖ¾õðùγ¼Á(substantia granulofilamentosa)¤È¤·¤ÆºÙ˦¼ÁÆâ¤ËÀ÷¿§, ƱÄꤵ¤ì¤ë.

ÌÖ¾õÀÖ·ìµå¤ÎÁý¸º¤Ï¹ü¿ñ¤·ì¾õÂÖ¤òɾ²Á¤¹¤ë¤è¤¤»ØÉ¸¤Ç¤¢¤êAA, ¹³Çò·ìÉÂÌôÅêÍ¿¸å, ½Å¾É´¶À÷¾É¶Ë´ü¤Ê¤É¤·ìÄã²¼¤Î»þ¤Ï¸º¾¯¤·, Å´·ç˳À­ÉÏ·ì, ½Ð·ì, ÍÏ·ìÀ­ÉÏ·ì¤Ê¤É¤Ç¤ÏÁý²Ã¤¹¤ë.

Å´·ç˳À­ÉÏ·ì¤äµðÀÖ²êµåÀ­ÉÏ·ì¼£ÎÅ»þ¤Ë¤ÏHb¤ÎÁý²Ã¤ËÀè¹Ô¤·¤Æ°ì²áÀ­¤ËÁý²Ã¤¹¤ë. ¼£ÎŸú²Ì¤¢¤ê¤Î¼ê¤¬¤«¤ê¤Ë¤Ê¤ë.

Àµ¾ïÃÍ¤Ï Àµ¾ïÀ®¿Í¤Ç 5-10¢ó, ¿·À¸»ùÀ¸¸å1½µ´Ö°ÊÆâ¤Ç¤Ï2-56¢ó¡ÊÊ¿¶Ñ21¢ó)

À®¿Í¤Ç¤Ï1Æü¤Ë2000²¯¸Ä¤ÎÀÖ·ìµå¤¬¹ü¿ñ¤Ç»ºÀ¸¤µ¤ìÁ´¿È¤ËÀ䤨´Ö¤Ê¤¯»ÀÁǤò¶¡µë¤·¤Æ¤¤¤ë.

 

Erythroblastic island ÀÖ²êµå·ìÅç

erythroblastic-island01.jpg(80.9KB)erythroblastic-island02.jpg(97.0KB)nurse_cell.jpg(67.1KB)
erythroblastic islanderythroblastic islandnurse cell

AML-M7¤Î¹ü¿ñÀ¸¸¡¥¿¥Ã¥ÁɸËܤˤߤé¤ì¤¿Erythroblastic island.

ÀÖ²êµå·ìÅç¡§Erythroblastic island

  • ÀÖ²êµå¤¬Ãæ¿´¥Þ¥¯¥í¥Õ¥¡¡¼¥¸(nurse cell)¤Î¼þ°Ï¤ËÀÜÃ夷¤¿·Á¤Çǧ¤á¤é¤ì¤ë¹½Â¤. Ãæ¿´¥Þ¥¯¥í¥Õ¥¡¡¼¥¸¤ÏÈó¾ï¤ËÁ¡ºÙ¤ÊºÙ˦¼ÁÆÍµ¯¤ÇÀÖ²êµå¤òÊñ¤ó¤Ç¤¤¤ë. ÀÖ²êµå¤Ë¤ÏÍļãºÙ˦¤«¤éÀ®½Ï¤·¤¿ÀÖ²êµå¤Þ¤Ç¼ï¡¹¤Îʬ²½Ãʳ¬¤ÎºÙ˦¤¬Ç§¤á¤é¤ì¤ë.¹ü¿ñÆâ¤ËÀÖ²êµåÅç¤È¤è¤Ð¤ì¤ë¾®½¸ÃĤò·ÁÀ®¤·¤Æ¤¤¤ë¡£
     
  • Ãæ¿´¥Þ¥¯¥í¥Õ¥¡¡¼¥¸¤ÈÀÖ²êµå¤Ï¥«¥ë¥·¥¦¥à°Í¸À­ÀÜÃå°ø»Ò¤ÇÀÜÃ夷¤Æ¤¤¤ë. HE, Naphtol-ASD-CAEÀ÷¿§¤Î¹ü¿ñÁÈ¿¥¤Ç¤ÏƱÄ꤬º¤Æñ¤ÇÀÖ²êµå¤Î¤ß¤·¤«³Îǧ¤Ç¤­¤Ê¤¤¤³¤È¤¬¤Û¤È¤ó¤É.
     
  • Ãæ¿´¥Þ¥¯¥í¥Õ¥¡¡¼¥¸¤ÏVCAM-1¤òȯ¸½,ÀÖ²êµå¤Ëȯ¸½¤¹¤ëVLA-4¤Î¦Á4-integrin¤ÈÀÜÃ夹¤ë.
     
  • ¥Þ¥¯¥í¥Õ¥¡¡¼¥¸¤«¤é»ºÀ¸¤µ¤ì¤ëIL-1,IFN-¦Ã,TNF-¦Á,GM-CSF,G-CSF¤Ï¹ü¿ñ¤·ì¤òж¿Ê¤µ¤»¤ë°ìÊý¤ÇÀÖ·ìµå¤·ì¤Ë¤ÏÍÞÀ©Åª¤ËºîÍѤ¹¤ë.
     
  • ÀÖ²êµå·ìÅç¤Ï¹üμþ°Ï¤Ë¤Ï¤Û¤È¤ó¤Éǧ¤á¤é¤ì¤º, ¹üμþ°Ï¤Ë¿¤¤ðùγµå·Ï¤·ìÁã¤ÈÂоÈŪ¤Ç¤¢¤ë.
  • ÀÖ²êµå·ìÅ礬¹üμþ°Ï¤Ë¸ºß¤¹¤ë½ê¸«¤Ï°Û¾ï. MDS¤Ê¤É¤Ëǧ¤á¤é¤ì¤ë abnormal localizaion of immature precursor(ALIP)¤ËÁêÅö¤¹¤ë.
 
  • ÀÖ²êµåÅç¤ÏÀÅ̮ƶ¤Ë¶áÀܤ·¤ÆÂ¸ºß¤¹¤ë¤³¤È¤¬Â¿¤¯, Àµ¾ï¹ü¿ñ¤ÎÀÖ²êµåÅç¤ÏÊ¿¶Ñ22.5¸Ä¤ÎÀÖ²êµå¤«¤é¤Ç¤­¤Æ¤¤¤ë¡£
  • Á°ÀÖ²êµåproerythroblast¤ÏñÆÈ, ¸ÉºßÀ­¤Ë¸ºß¤¹¤ë·¹¸þ¤¬¶¯¤¯, ʬ²½¤¬¤¹¤¹¤ó¤ÀÀÖ²êµå¤Ç¹½À®¤µ¤ì¤ë·ìÅç¤Û¤ÉÂ礭¤¯¤Ê¤ë.
  • æ·ì»É·ã¤Ç¤Ï, ·ìÃæ¥¨¥ê¥¹¥í¥Ý¥¨¥Á¥óÇ»ÅÙ¤¬¹â¤¤¤Û¤ÉÀÖ²êµå·ìÅ礬½¸¹ç¤·ÀÖ²êµå·Ï¤·ìÁã¤Ï³ÈÂ礹¤ë.
     
  • ÍÏ·ìÀ­ÉÏ·ì¤Ç¤Ï¹ü¿ñ¤ËÂå½þÀ­ÀÖ·ìµå·Ï¤·ìж¿Ê¤¬¤ª¤³¤êÀÖ²êµå¿ô¤¬Áý²Ã¤·ÀÖ²êµåÅç¤ÏÂ礭¤¯¤Ê¤ë¡£
     
  • ºÆÀ¸ÉÔÎÉÀ­ÉÏ·ì, ¹ü¿ñÀþ°Ý¾É¤Ç¤ÏÀÖ²êµåÅç¤ÎÀÖ²êµå¿ô¤Ï¸º¾¯¤·¤Æ¤¤¤ë¡£
     
  • ¹ü¿ñ¤Ë¤ÏÊ¿¶ÑÀÖ·ìµå»ºÀ¸¤ÎÌó7ÇܤÎÀÖ·ìµåÀ¸»ºÍ½È÷ǽÎϤ¬¤¢¤ë¤È¤¤¤ï¤ì¤Æ¤¤¤ë

ÀÖ·ìµå¤·ì-ÀÖ²êµå¤Îʬ²½¤ÈÁý¿£

Âè13²ó¹ü¿ñÉÂÍý¸¦µæ²ñ¡ÖÀÖ²êµå¡×ÅìËÌÂç³ØÂç³Ø±¡°å³Ø·Ï¸¦µæ²Ê¡¡Ä¥ÂØ ½¨ÏºÀèÀ¸¤Î¹Ö±é¤è¤ê

3factors of erythropoiesis.jpg
 

ÀÖ·ìµå¤·ì erythropoiesis¤Î½ÅÍפÊ3¤Ä¤Î°ø»Ò

1. ÀÖ·ìµå¤·ì¤ÎÆâŪ°ø»Ò---GATA1, GATA2ž¼Ì°ø»Ò¤È¤½¤ÎÊ£¹çÂΤ¬¼çÌò

2. ÀÖ·ìµå¤·ì¤Î³°Åª°ø»Ò---erythropoietin¤¬¼çÌò

3. globinÎ̤òÄ´Àᤷ¤Æ¥Ø¥à¡¦¥°¥í¥Ó¥ó¤¬Àµ³Î¤ËƱÎ̤λÍÎÌÂΤò·ÁÀ®¤¹¤ë---Heme¤¬¼çÌò

°Ê¾å¤Î3¤Ä¤Î°ø»Ò¤¬ÀÖ·ìµå¤·ì¤Ë½ÅÍפÊÌò³ä¤ò²Ì¤¿¤·¤Æ¤¤¤ë¡£

ÀÖ·ìµå¤·ì¤ÎÆâŪ°ø»Ò

GATAž¼Ì°ø»Ò·²¡¡GATA transcription factors

GATAž¼Ì°ø»Ò¤Ï,GATA-1¤«¤éGATA-6¤Î6¼ïÎबÊó¹ð¤µ¤ì¤Æ¤¤¤ë.

  • ÆÃħ¤È¤·¤Æ,¤¹¤Ù¤Æ¤ÎGATAž¼Ì°ø»Ò¤¬Å¾¼Ì¤ÎÀ©¸æÎΰè¤Ç¤¢¤ëpromoter¤Þ¤¿¤Ï enchancer¤ÎGATA±ö´ðÇÛÎó¤òǧ¼±¤·¤Æ·ë¹ç,²¼Î®¤Ë¤¢¤ëɬÍפʰäÅÁ»Ò¤Îž¼Ì¤òON¤Ë¤¹¤ë¡£
     
  • ¤·¤«¤·,GATAž¼Ì°ø»Ò¤Ë¤è¤êµ¡Ç½¤·¤Æ¤¤¤ëºÙ˦·ÏÎó, ÁÈ¿¥·ÏÎ󤬰ۤʤäƤ¤¤ë.
    GATAswitch.jpg

    GATA1(Xp11.23): ÀÖ·ìµå·Ï, µð³Ëµå, ÈîËþºÙ˦, ¹¥»Àµå¤Ëȯ¸½.
    GATA2(3q21.3): ¤·ì´´ºÙ˦, ¤·ìÁ°¶îºÙ˦(µð³Ëµå, ÈîËþºÙ˦¤Ê¤É)
    GATA3: T¥ê¥ó¥Ñµå
    (GATA1-3¤Ï¤·ì·ÏGATAž¼Ì°ø»Ò;hematopoietic GATA transcription factors¤È¤â¸Æ¤Ð¤ì¤ë)
    GATA4,GATA5,GATA6: ¿´Â¡¤Ê¤ÉÆâæõÍÕͳÍèºÙ˦¡¡¡ÊGATA3¤â¡Ë

  • GATA-2¤Ï¤·ì´´ºÙ˦¤Ëȯ¸½¤·,´´ºÙ˦¤Î°Ý»ý, Áý¿£¤Ë½ÅÍפÊÌò³ä¤ò¤Ï¤¿¤¹*5
     
  • GATA-1¤Ï°ìÉôGATA-2¤Èȯ¸½¤¬½ÅÊ£¤¹¤ë¤¬, GATA-2¤Ë¼¡¤¤¤Çȯ¸½¤·ÀÖ²êµå, µð³Ëµå, ¹¥»Àµå, ÈîËþºÙ˦¤Îʬ²½¤Ë´ØÍ¿¤¹¤ë.
     
  • GATA-3¤ÏTºÙ˦ʬ²½¤Ë½ÅÍ×*6¤Ç¤¢¤ë.
     
  • ÀÖ·ìµå·Ï¤Ç¤Ïʬ²½¤Ëȼ¤Ã¤ÆGATA2¤ÈGATA1¤Îȯ¸½Î̤¬ÊѲ½¤·¡¢ÍÍ¡¹¤ÊÀÖ·ìµå·Ï¤Î°äÅÁ»Òȯ¸½¤òÀ©¸æ¤·¤Æ¤¤¤ë¡£

GATA switch

¤·ìÁ°¶îºÙ˦¤Ë¤ª¤¤¤ÆGATA-2¤Ï¼«Ê¬¼«¿È¤ò³èÀ­²½¤¹¤ë¤È¤È¤â¤ËGATA-1¤ò³èÀ­²½¤¹¤ë. °ìÊýGATA-1¤ÏGATA-2¤Îȯ¸½¤òÍÞÀ©¤·ÀÖ·ìµåʬ²½¤Î²áÄø¤Ë¤ª¤¤¤ÆGATA-2¤«¤éGATA-1¤Ø¤Îȯ¸½°Ü¹Ô¤¬¹Ô¤ï¤ì¤ë. *7*8*9

GATA1control.jpg

GATA1¤Îµ¡Ç½¤ÈÊ£¹çÂÎ

GATA1¤ÏÀÖ·ìµå¤·ì¤Ëɬ¿Ü¤Îž¼Ì°ø»Ò.

transferrin receptor, ferritin, mitoferrin, ¤¹¤Ù¤Æ¤Î¥Ø¥à¹çÀ®·Ï°äÅÁ»Ò, ¥°¥í¥Ó¥ó,ÀÖ·ìµåËìÀ®Ê¬,¥¨¥ê¥¹¥í¥Ý¥¤¥¨¥Á¥ó¼õÍÆÂÎ, etc ¤¹¤Ù¤Æ¤ÎÀÖ·ìµå´ØÏ¢°äÅÁ»Òȯ¸½¤¬GATA1¤ÎÀ©¸æ²¼¤Ë¤¢¤ë.
GATA1¤ÏÀÖ·ìµå¤¬ÀÖ·ìµå¤é¤·¤¯¤Ê¤ë¤¿¤á°äÅÁ»Ò¤Îž¼Ì¤ò¤Ë¤Ê¤Ã¤Æ¤¤¤ë¥Þ¥¹¥¿¡¼°äÅÁ»Ò¤Ç¤¢¤ë.

GATAž¼Ì°ø»Ò¤ÏñÆÈ¤Îž¼Ì°ø»Ò¤Î¤ß¤ÇÀÖ·ìµå¤Î°äÅÁ»Ò¤òž¼Ì¤Ç¤­¤ë¤ï¤±¤Ç¤Ï¤Ê¤¯GATAž¼Ì°ø»Ò¤¬Ãæ¿´¤È¤Ê¤êÊ£¹çÂΤò¤Ä¤¯¤ê¤³¤ÎÊ£¹çÂΤ¬ÀÖ·ìµå¤ÎÆÃ°ÛŪ°äÅÁ»Ò¤Îž¼Ì¤ò¤Ë¤Ê¤Ã¤Æ¤¤¤ë¡£

Ê£¹çÂÎÃæ¤ÎETO2, LMO2¤ÎƯ¤­*10

ETO-2; ETO family¤Ë°¤¹¤ë³Ë¥¿¥ó¥Ñ¥¯¼Á*11

  • ž¼ÌÍÞÀ©ºîÍѤò¤â¤Ä(class I HDAC)¡¨¥Ò¥Èex vivoÀÖ²êµå¤ÇETO-2¤òknock down¤¹¤ë¤ÈHb¦Â, ¦Á¤Îȯ¸½¤¬¾å¤¬¤ë.(ʬ²½¤¬¤¹¤¹¤à)
  • ÀÖ²êµå, µð³Ëµåʬ²½¤ª¤è¤Ó¤·ì´´ºÙ˦¤Îµ¡Ç½¤Ë´ØÏ¢¤·¤Æ¤¤¤ë¡£

LMO-2*12

  • knock down¤Ë¤è¤êETO2¤ÈµÕ¤ËHb¦Â, ¦Á¤Îȯ¸½¤¬Äã²¼¤¹¤ë.
  • ¥¿¥ó¥Ñ¥¯¤ò¸º¾¯¤µ¤»¤ë¤È, GATA1¤äSCL/TAL1¤ÎÎ̤ÏÊѤï¤é¤Ê¤¤¤¬LMO2¤Ë¤¯¤Ã¤Ä¤¯Î̤¬¸º¤ë.
    GATAž¼Ì°ø»ÒÊ£¹çÂΤò¤¯¤Ã¤Ä¤±¤Æ¤¤¤ë¥¿¥ó¥Ñ¥¯¼Á

Ê£¹çÂΤÏGATA1¤òÃæ¿´¤Ë·ÁÀ®¤µ¤ì¤Æ¤¤¤ë¤¬, LMO2¤¬Ê£¹çÂΤò¤Î¤ê¤Å¤±¤·¤¿¤ê, ž¼Ì»É·ã¤¬É¬Íפʤ¤¾ì¹ç¤ÏETO2¤¬Æþ¤Ã¤Æ¤­¤ÆÅ¾¼Ì¤òÍÞÀ©¤¹¤ë¤è¤¦¤ËƯ¤¯*10.

 

GATA1-SLC.jpg¡¡GATA1complex.jpg

 
 

ÀÖ·ìµå¤·ì¤Î³°Åª°ø»Ò Erythropoietin

 
Epo-erythroid cells.jpg

Erythropoietin; ³°¤«¤é¤ÎÀÖ·ìµå¤·ì¤Î¥Þ¥¹¥¿¡¼°ø»Ò.

Epo¤ÏÅüº¿¤òË­É٤˴ޤà34kDa¤ÎÅü¥¿¥ó¥Ñ¥¯¼Á¤Ç, ÀÖ²êµå·ÏÁ°¶îºÙ˦¤ä¥Ø¥â¥°¥í¥Ó¥ó¹çÀ®¤ò¤Ï¤¸¤á¤ëÁ°¤ÎÀÖ²êµå¤ËºîÍѤ·¤ÆÀÖ·ìµå¤·ì¤òж¿Ê¤µ¤»¤ë.*13

¿À·Ð·ÏºÙ˦¤Ë¤ª¤¤¤ÆºÙ˦ÊݸîºîÍѤ¬Ç§¤á¤é¤ì¤Æ¤¤¤ë.*13

 

Renal EPO-producing cells¡ÊREPºÙ˦)

º£¤Þ¤Ç¤Ï¿Õ¡¤Î¤É¤ÎºÙ˦¤¬EPO¤ò¤Ä¤¯¤ë¤«¤ï¤«¤Ã¤Æ¤Ê¤«¤Ã¤¿¤¬¥È¥é¥ó¥¹¥¸¥§¥Ë¥Ã¥¯¥Þ¥¦¥¹¤Î¼Â¸³·Ï¤Ç ´Ö¼ÁºÙ˦¤ÎÀþ°Ý²êºÙ˦ÍͺÙ˦¤¬»ºÀ¸¤·¤Æ¤¤¤ë¤³¤È¤¬Êó¹ð¤µ¤ì¤¿. *14

  • Renal EPO-producing cells¡ÊREPºÙ˦); CD73+, PDGFR¦Â+ = peritubular fibroblasts(¿ÕÈé¼Á´Ö¼ÁÀþ°Ý²êºÙ˦[ÍÍ]ºÙ˦)
  • glycolysis genes¤Îneural isoform, Glut3, Aldoc and Pfkfb3°äÅÁ»Ò¤Ê¤É¤òȯ¸½¤·¤Æ¤¤¤ë.
 

¤Ê¤¼»ÀÁÇʬ°µ¤¬²¼¤¬¤ë¤È(ÉÏ·ì), EPO¤¬»ºÀ¸¤µ¤ì¤ë¤Î¤«

·ò¹¯¤ÊÀ®¿Í¹ü¿ñÃæ»ÀÁÇÇ»ÅÙ¤Ï 7%¤Ç, ÉÏ·ì¤Ë¤Ê¤ë¤È1%¤Þ¤ÇÄã²¼¤¹¤ë¤³¤È¤¬Êó¹ð¤µ¤ì¤Æ¤¤¤ë. Äã»ÀÁǤˤè¤ê³èÀ­²½¤µ¤ì¤ëž¼Ì°ø»ÒHIF(hypoxia-induced factor)¤Ë¤è¤ê¿Õ¡¤Ç¤Î¥¨¥ê¥¹¥í¥Ý¥¨¥Á¥ó»ºÀ¸¤¬Áý²Ã¤·, ÀÖ²êµå·Ï¸å´üÁ°¶îºÙ˦(CFU-E)¤ÎÁý¿£Ê¬²½¤¬Â¥¿Ê¤µ¤ì¤ë.-->HIF

 
 
 
 
 
 
 

*1  Íļã¤ÊºÙ˦¤¬¾­Í貿¤Ë¤Ê¤ë¤«¤ï¤«¤é¤Ê¤¤Ãʳ¬¤«¤éÆÃÄê¤Îµ¡Ç½¤ò¤â¤ÄÀ®½ÏºÙ˦¤Ë¤Ê¤Ã¤Æ¤¤¤¯²áÄø¤òʬ²½¤È¤¤¤¦
*2  ¿¹¹¯Íº¤Û¤« ¥Ò¥ÈÀÖ²êµå·ÏÆÃ°ÛŪÁ°¶îºÙ˦¤ÎƱÄê¡¡Î×¾²·ì±Õ 2016; 57: 585-591
*3  Mori Y, et al. Prospective isolation of human erythroid lineage-committed progenitors. Proc Natl Acad Sci U S A. 2015 Aug 4;112(31):9638-43.PMID:26195758
*4  Wood B. Multicolor immunophenotyping: human immune system hematopoiesis. Methods Cell Biol. 2004;75:559-76.PMID:15603442
*5  Tsai FY, et al. An early hematopoietic defect in mice lacking the transcription factor GATA-2 Nature 1994; 371: 221-226
*6  Ting CN, et al. Transcription factor GATA-3 is required for development of the T-cell lineage.Nature. 1996 Dec 5;384(6608):474-8.
*7  Bresnick EH, et al. GATA switches as developmental drivers. J Biol Chem. 2010;285: 31087-31093.
*8  Bresnick EH, et al. Developmental control via GATA factor interplay at chromatin domains. J Cell Physiol. 2005;205: 1-9.
*9  Kaneko H, et al. GATA factor switching during erythroid differentiation. Curr Opin Hematol. 2010; 17: 163-168.
*10  Fujiwara T et al. Building multifunctionality into a complex containing master regulators of hematopoiesis. Proc Natl Acad Sci U S A. 2010 Nov 23;107(47):20429-34.
*11  Fujiwara T et al. Role of transcriptional corepressor ETO2 in erythroid cells. Exp Hematol. 2013 Mar;41(3):303-15.e1.
*12  Inoue A, et al.Elucidation of the role of LMO2 in human erythroid cells. Exp Hematol. 2013 Dec;41(12):1062-76.e1.
*13  Siren AL, et al. Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress. Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):4044-9.
*14  Yamazaki S,et al A mouse model of adult-onset anaemia due to erythropoietin deficiency. Nat Commun. 2013;4:1950.

źÉÕ¥Õ¥¡¥¤¥ë: filenurse_cell_s.jpg 153·ï [¾ÜºÙ] filenurse_cell.jpg 355·ï [¾ÜºÙ] filenurse cell_s.jpg 140·ï [¾ÜºÙ] filenurse cell.jpg 143·ï [¾ÜºÙ] fileerythroblastic-island02_s.jpg 135·ï [¾ÜºÙ] fileerythroblastic-island02.jpg 397·ï [¾ÜºÙ] fileerythroblastic-island01_s.jpg 137·ï [¾ÜºÙ] fileerythroblastic-island01.jpg 484·ï [¾ÜºÙ] filerevised-human EP.jpg 1135·ï [¾ÜºÙ] fileEpo-erythroid cells.jpg 1948·ï [¾ÜºÙ] fileGATA1complex.jpg 871·ï [¾ÜºÙ] fileGATA1-SLC.jpg 777·ï [¾ÜºÙ] fileGATA1control.jpg 925·ï [¾ÜºÙ] filereticulocyte.jpg 1264·ï [¾ÜºÙ] fileGATAswitch.jpg 2815·ï [¾ÜºÙ] file3factors of erythropoiesis.jpg 1065·ï [¾ÜºÙ] fileerythroblast.jpg 2498·ï [¾ÜºÙ]

¥È¥Ã¥×   º¹Ê¬ ¥Ð¥Ã¥¯¥¢¥Ã¥× ¥ê¥í¡¼¥É   °ìÍ÷ ñ¸ì¸¡º÷ ºÇ½ª¹¹¿·   ¥Ø¥ë¥×   ºÇ½ª¹¹¿·¤ÎRSS
Last-modified: 2021-01-06 (¿å) 10:50:16 (58d)