Human Stem Cells/HSC & Development （人类干细胞和造血干细胞及其发育）

 

【sperm (精子)+ ovum (卵子)】 （fertilization 受精）→ zygote (受精卵，合子) → 4/8/16 cell stage (4/8/16细胞期)  →   blastocyst (囊胚) (trophoblast滋养层  blastocoel胚囊腔  inner cell mass 内细胞团)   →→→郑州大学一附院血液内科万鼎铭

?：gastrula(原肠胚期)（ectoderm外胚层 mesoderm中胚层endoderm内胚层）→      fetus(胎儿) [somatic stem cell 成体干细胞（self renewal自我更新）   →     terminally differentiated cell type (终末分化的细胞类型) (inducible expression of transcription factors转录因子的诱导表达：oct-4, sox2, c-myc, klf4 etc)]   →      induced pluripotent stem cell (ipsc 诱导多能干细胞)

?：embryonic stem cells （esc胚胎干细胞）（self renewal自我更新）

 

【esc（胚胎干细胞）or ipsc（诱导多能干细胞）】(cd9，cd15，cd24，cd29，cd30，cd49f, cd133，cd324，cd338，ccr4，frizzled-5, gctm-2, podocalyxin, ssea-3, ssea-4, tra-1-60 antigen, tra-1-18 atigen etc)  →→→

?：primitive streak (原条) →→

1. mesodermal embryonic stem cell(中胚层胚胎干细胞)(cd31,cd34,cd325) → immature mesoderm(未成熟中胚层) →→

①paraxial mesoderm(轴旁中胚层) → hemangioblast(成血管血液干细胞)（cd31,cd34,cd133,cd143,cd144,cd202b,cd309,cd324,ephb4,podocalyxin）→  a.  hematopoietic stem cell (造血干细胞) ( cd34, cd38^-, cd90, cd105, cd106, cd117, cd133, cd164, cd184, cd202b, cd338, flk-1, notch-1)    b.    endothelial cells(内皮细胞) (cd31,cd34,cd62e,cd105,cd106) → hematopoietic stem cell (造血干细胞)

② lateral mesoderm(侧中胚层) (cd5, cd10, cd13, cd14, c15, cd29, cd31, cd44, cd49d, cd49f, cd54, cd71, cd72, cd73, cd90, cd105, cd106, stro-1) → mesenchymal stem cell (间充质干细胞)（cd44, cd45^-, cd73, cd90, cd105, cd166） → cartilage软骨, fibroblast成纤维细胞(tendon腱 & ligament韧带 &  skin皮肤),stromal cell基质细胞, osteocyte骨细胞, astrocyte星形胶质细胞, adipocyte脂肪细胞, myocyte肌细胞（cardiac muscle, smooth muscle, skeletal muscle）

 

【hematopoietic stem cell (hsc造血干细胞)】( cd34, cd38^-, cd90, cd105, cd106, cd117, cd133, cd164, cd184, cd202b, cd338, flk-1, notch-1) →→→

㈠ common lymphoid progenitor(淋系祖细胞)（cd10,cd34,cd38）→lymphoblast（原始淋巴细胞，成淋巴细胞，淋巴母细胞）→ prolymphocyte (幼稚淋巴细胞，前淋巴细胞→natural killer cell 自然杀伤细胞)→ small lymphocyte （小淋巴细胞）→→

① b lymphocyte (b 淋巴细胞)→ mature b-cell （成熟b细胞）：包括memory b-cell；igm secreting b-cell（分泌igm）；switched plasma cell (转换浆细胞→ 分泌iga, igd, ige, igg)

② t lymphocyte (t 淋巴细胞) →tc cell (cd8⁺,tcrα/β → t-memory cell)；th cell (cd4⁺,tcrα/β→ th1，th2，th9，th17.th22，treg调节性t细胞，t-memory cell)

㈡ common myeloid progenitor(髓系祖细胞) （cd34,cd38,cd123,cd45ra^-）→→

① granulocyte-monocyte progenitor(gmp粒-单祖细胞)（cd34,cd38,cd123,cd45ra）→ myeloblast(原始粒细胞，成髓细胞)（cd13,cd15,cd33,cd91,cd114,cd116）→→

⑴ neutrophilic promyelocyte(中性早幼粒细胞) → neutrophilic myelocyte(中性中幼粒细胞) → neutrophilic metamyelocyte(中性晚幼粒细胞) → neutrophil (嗜中性粒细胞)[neutrophilic band, neutrophilic stab form/cell, neutrophilic granulocyte band form（中性杆状核粒细胞）；neutrophilic segmented granulocyte/cell, neutrophilic granulocyte segmented form,segmented neutrophil(中性分叶核粒细胞)]

⑵ eosinophilic promyelocyte(嗜酸性早幼粒细胞) →eosinophilic myelocyte(嗜酸性中幼粒细胞) →eosinophilic metamyelocyte(嗜酸性晚幼粒细胞) → eosinophil (嗜酸性粒细胞)[eosinophilic band, eosinophilic stab form/cell, eosinophilic granulocyte band form（嗜酸性杆状核粒细胞）；eosinophilic segmented granulocyte/cell, eosinophilic granulocyte segmented form,segmented eosinophil(嗜酸性分叶核粒细胞)]

⑶ basophilic promyelocyte(嗜碱性早幼粒细胞) →basophilic myelocyte(嗜碱性中幼粒细胞) →basophilic metamyelocyte(嗜碱性晚幼粒细胞) → basophil (嗜碱性粒细胞) [basophilic band, basophilic stab form/cell, basophilic granulocyte band form（嗜碱性杆状核粒细胞）；basophilic segmented granulocyte/cell, basophilic granulocyte segmented form,segmented basophil(嗜碱性分叶核粒细胞)]

⑷ monoblast (原始单核细胞) →  promonocyte（幼稚单核细胞）→  monocyte（单核细胞 → macrophage/phagocyte 巨噬细胞；myeloid dendritic cell 髓系树突状细胞)

② megakaryocyte-erythroid progenitor (mep 巨-红祖细胞)( cd34, cd38, cd123^-，cd45ra^-) →→

⑴ promegakaryoblast(前原始巨核细胞) → megakaryoblast (原始巨核细胞) → promegakaryocyte（幼稚巨核细胞）→   megakaryocyte（巨核细胞）[granular megakaryocyte颗粒型巨核细胞，platelet-forming/producing megakaryocyte产板型巨核细胞，nude nucleated megakaryocyte裸核型巨核细胞] → thrombocyte（platelet血小板，血栓细胞）

⑵ proerythroblast (原始红细胞)(cd71, cd105, glycophorin血型糖蛋白) → basophilic erythroblast（早幼红细胞）→  polychromatic erythroblast（中幼红细胞）→orthochromatic erythroblast（晚幼红细胞）→ polychromatic erythrocyte （嗜多色性红细胞）→  erythrocyte（红细胞）

③ mastoblast/tissue mastoblast(原肥大细胞/原组织嗜碱细胞)→  promastocyte/tissue promastocyte (幼肥大细胞/幼组织嗜碱细胞)→ mastocyte(mast cell)/tissue  basophil (肥大细胞/组织嗜碱细胞)

2. primitive endoderm（原始内胚层）（cd325）→ definitive endoderm (定形内胚层) (cd184) → lung肺, intestine肠, pancreas胰腺, thyroid甲状腺, liver肝脏, thymus胸腺

?：ectoderm(外胚层) (ncam,notch1) →→→

⑴ neural tube (神经管) (cd15, cd49f, cd57, cd81, cd95, cd146, cd184, cd271, cd288, cd349, abcg2, neuroglycan-c, neuropilin-2, notch1) → motor neuron运动神经元,  spinal cord脊髓, neural pituitary神经垂体, retina视网膜, brain脑

⑵ neural crest(神经嵴)(cd49d, cd57, cd271, notch1) → dentine of teeth牙本质, facial cartilage面部软骨, adrenal medulla肾上腺髓质, melanocyte黑色素细胞, peripheral nervous system(周围神经系统) →(schwann cell许旺细胞, parasympathetic nervous system副交感神经系统, neuroglia神经胶质, sympathetic nervous system交感神经系统)

⑶ outer ectoderm/epidermis(外胚层) (cd71, p63) →  lens and cornea晶状体和角膜, epidermis(skin)表皮/上皮, hair毛发, nail指甲/趾甲, sebaceous gland皮脂腺, olfactory epithelium嗅觉上皮, mouth epithelium 口腔上皮（→anterior pituitary垂体前叶, tooth enamel牙釉质/牙珐琅质, cheek epithelium颊上皮）